BLOGSCAN - How the healthcare blogosphere was scammed

Scams in healthcare are not just limited to insurers, hospitals and clinicians. The blogosphere itself can be victimized.

At Dr. Val's blog "Getting Better" in a post entitled "How The Health Blogosphere Was Scammed", we learn that a blog aggregator company called Wellsphere promised to help bloggers better distribute their content, achieve higher recognition, etc. It sent out seductive, complementary letters made to appear as if done individually, and an invitation to submit content with the following onerous provision in the electronic fine print (only seen if a 'terms of service' link is clicked):

When you post your own copyrightable content on the Website or give Wellsphere permission to post your copyrightable content on the Website, you retain ownership of any copyright you claim to your submitted content. However, by posting your content or giving Wellsphere permission to post your content you automatically grant Wellsphere a royalty-free, paid-up, non-exclusive, worldwide, irrevocable, perpetual license to (i) use, make, sell, offer to sell, have made, and further sublicense any such User Materials, and (ii) reproduce, distribute, create derivative works of, publicly perform and publicly display the User Materials in any medium or format, whether now known or later developed…

In other words, you retain your copyright to your IP, except grant the company the ability to do anything they want with your material, with no reimbursement to you if they make money, and you also allow the company to distribute and sublicense your material to anyone they please, your copyright be damned.

One wonders if they would appreciate such 'fine print' in a patient informed consent form:

"During the surgery you retain ownership of your organs, but if we find one we like we reserve the right to sell it to someone else for their own use."

The company was then sold, and bloggers found themselves estranged from benefit and control of their own IP.

The following list of posts on this issue comes from Deliberate Ambiguity:


Hedge funds, anyone? I know a good one that promises 12% returns every year, even in economic downturns, that uses a secret strategy for investing developed by some genius level programmers.

-- SS

Seafood and Vitamin K2

In his travels around the globe, Dr. Weston Price found that the most robust groups were often those who had access to marine and freshwater foods. For example, Polynesian groups had a tooth decay prevalence as low as 0.6% of teeth. That's roughly one in 5 people with even a single cavity, in a population that doesn't brush its teeth, drink fluoridated water or go to the dentist. These individuals had broad dental arches, straight teeth, and fully erupted wisdom teeth as well.

As soon as they adopted white flour and sugar as dietary staples, the tooth decay prevalence of Polynesian groups went as high as 33.4% of teeth, or about 11 cavities per person. This represents a 5,600% increase in the prevalence of tooth decay. The next generation to be born also suffered from characteristic facial and skeletal abnormalities that are common in modern societies to varying degrees.

This leads me to ask the question, what is unique about seafood that allows it to support excellent development and maintenance of the human body? Seafood has a lot of advantages. It tends to be very rich in minerals, particularly iodine which can be lacking in land foods. It's also a good source of omega-3 fatty acids and low but adequate in linoleic acid (omega-6). This impacts development and maintenance in a number of ways, from fat mass to dental health.

As I wrote in the last post and others, I believe that one of the major determinants of proper development and continued health is the diet's content of the fat-soluble vitamins A, D and K2. K2 in particular is rare in the modern diet. We're also deficient in vitamin D because of our indoor lifestyles and use of sunscreen. Polynesians didn't have to worry about vitamin D because they spent much of the day outside half naked.

How about K2? Is seafood a good source? At first glance, it doesn't appear to be. Mackerel is the best source I came across on NutritionData, with one serving delivering 5.6 micrograms of vitamin K. It wasn't specified, but only a portion of that will be vitamin K2 MK-4, with the majority probably coming from K1. Most other types of fish have very low levels of vitamin K.

But we have to probe deeper. Nutrition information for fish refers to muscle tissue. Muscle is a poor source of K2 in mammals, could that be the case in fish as well? It turns out, the organs are the best source of K2 MK-4 in fish, just as they are in mammals. It's most concentrated in the liver, kidneys, heart and gonads. This loosely resembles the situation in mammals, which also retain MK-4 in their kidneys and gonads (along with pancreas, salivary glands, and brain).

I don't know how frequently traditional non-industrial cultures ate fish organs. My guess is they discarded most of them as do modern cultures, because they smell funny and putrefy rapidly. There are some exceptions, however. Certain traditional cultures ate fish livers, cod for example. Price described a dish eaten by a healthy, isolated Gaelic group in Nutrition and Physical Degeneration:
An important and highly relished article of diet has been baked cod's head stuffed with chopped cod's liver and oatmeal.
Gonads are one of the richest sources of K2 MK-4 in fish, containing 5-10 micrograms of MK-4 per kilogram of tissue in a few different species (according to this paper). Even that is not really an impressive concentration.

One thing that is universally relished by traditional groups is fish eggs, which of course develop from the gonads. A number of cultures dried fish eggs, sometimes trading them far into the interior. Although they haven't been analyzed for MK-4 content in modern times, Price found fish eggs to be a rich source of K2. Speaking of vitamin K2, he said: "its presence is demonstrated readily in the butterfat of milk of mammals, the eggs of fishes and the organs and fats of animals". Unfortunately, Price's assay was not quantitative so we don't have numbers.

As mainstream medicine slowly catches up to the importance of vitamin K2 MK-4 that Price described in the 1940s, more foods are being tested. I think we'll see values for fish eggs in the near future. This will allow us to discriminate between two possibilities: 1) seafood is a good source of K2, or 2) the human requirement for K2 is not particularly high in the context of an otherwise healthy diet.

Seafood and Vitamin K2

In his travels around the globe, Dr. Weston Price found that the most robust groups were often those who had access to marine and freshwater foods. For example, Polynesian groups had a tooth decay prevalence as low as 0.6% of teeth. That's roughly one in 5 people with even a single cavity, in a population that doesn't brush its teeth, drink fluoridated water or go to the dentist. These individuals had broad dental arches, straight teeth, and fully erupted wisdom teeth as well.

As soon as they adopted white flour and sugar as dietary staples, the tooth decay prevalence of Polynesian groups went as high as 33.4% of teeth, or about 11 cavities per person. This represents a 5,600% increase in the prevalence of tooth decay. The next generation to be born also suffered from characteristic facial and skeletal abnormalities that are common in modern societies to varying degrees.

This leads me to ask the question, what is unique about seafood that allows it to support excellent development and maintenance of the human body? Seafood has a lot of advantages. It tends to be very rich in minerals, particularly iodine which can be lacking in land foods. It's also a good source of omega-3 fatty acids and low but adequate in linoleic acid (omega-6). This impacts development and maintenance in a number of ways, from fat mass to dental health.

As I wrote in the last post and others, I believe that one of the major determinants of proper development and continued health is the diet's content of the fat-soluble vitamins A, D and K2. K2 in particular is rare in the modern diet. We're also deficient in vitamin D because of our indoor lifestyles and use of sunscreen. Polynesians didn't have to worry about vitamin D because they spent much of the day outside half naked.

How about K2? Is seafood a good source? At first glance, it doesn't appear to be. Mackerel is the best source I came across on NutritionData, with one serving delivering 5.6 micrograms of vitamin K. It wasn't specified, but only a portion of that will be vitamin K2 MK-4, with the majority probably coming from K1. Most other types of fish have very low levels of vitamin K.

But we have to probe deeper. Nutrition information for fish refers to muscle tissue. Muscle is a poor source of K2 in mammals, could that be the case in fish as well? It turns out, the organs are the best source of K2 MK-4 in fish, just as they are in mammals. It's most concentrated in the liver, kidneys, heart and gonads. This loosely resembles the situation in mammals, which also retain MK-4 in their kidneys and gonads (along with pancreas, salivary glands, and brain).

I don't know how frequently traditional non-industrial cultures ate fish organs. My guess is they discarded most of them as do modern cultures, because they smell funny and putrefy rapidly. There are some exceptions, however. Certain traditional cultures ate fish livers, cod for example. Price described a dish eaten by a healthy, isolated Gaelic group in Nutrition and Physical Degeneration:
An important and highly relished article of diet has been baked cod's head stuffed with chopped cod's liver and oatmeal.
Gonads are one of the richest sources of K2 MK-4 in fish, containing 5-10 micrograms of MK-4 per kilogram of tissue in a few different species (according to this paper). Even that is not really an impressive concentration.

One thing that is universally relished by traditional groups is fish eggs, which of course develop from the gonads. A number of cultures dried fish eggs, sometimes trading them far into the interior. Although they haven't been analyzed for MK-4 content in modern times, Price found fish eggs to be a rich source of K2. Speaking of vitamin K2, he said: "its presence is demonstrated readily in the butterfat of milk of mammals, the eggs of fishes and the organs and fats of animals". Unfortunately, Price's assay was not quantitative so we don't have numbers.

As mainstream medicine slowly catches up to the importance of vitamin K2 MK-4 that Price described in the 1940s, more foods are being tested. I think we'll see values for fish eggs in the near future. This will allow us to discriminate between two possibilities: 1) seafood is a good source of K2, or 2) the human requirement for K2 is not particularly high in the context of an otherwise healthy diet.

Pfizer/Wyeth Merger And Sacrificing The Future: "Laying Off Scientific Staff All Over The Place"

In yet another massive waste of money, Pfizer has been touting its merger with Wyeth via full page ads in major newspapers. I saw the ads yesterday in the Wall Street Journal and my local Philadelphia newspaper under this large self-aggrandizing banner in capitals:

CREATING THE WORLD'S PREMIER BIOPHARMACEUTICAL COMPANY

A website with the presumptuous name "www.premierbiopharma.com" has also been created.

What is pathetic is an apparent continuing belief that mergers of two companies in trouble
for essentially the same reasons can produce a company that is successful.

Each individual company has not been doing well despite billions in expenditures. They will continue not doing well despite the merger because they suffer an organic problem, namely, they both mismanage R&D.

This "merger = miracle" belief persists, in part, because those in charge are unable to see the problems that impair R&D. The problems are "hiding in plain sight." The reason the problems hide in plain sight from the leadership is that the leaders are blind.

Those in charge cannot see that which the domain specialist sees.

They cannot see because they lack the training, experience, and what is described as 'meta-competence' (in this brilliant article on competence) essential to seeing that which is obvious. Obvious, that is, to those who do not lack these characteristics. In addition, I've also observed that some lack the fundamental analytical abilities essential to understanding and managing the complexities of biomedical R&D.

Why those without domain expertise are in charge of organizations whose long term viability depends entirely on the most advanced and creative pursuit of biomedical 'miracles' is another matter. I won't address this here, other than saying it reflects the adverse consequences of a bias that has evolved in management "science." That bias is the belief that all the world consists of faceless labor resources performing easily definable processes upon interchangeable widgets, and that management can therefore be done by generic managers, exclusively. Some of the world is like that, but some isn't, such as biomedical R&D.

Management in the absence of domain expertise in this industry is, in fact, mismanagement.

There is nothing here to spin, there is nothing to debate. There is nothing to discuss. This is a first principle. Failure to accept this reality results in corporate failure.

Under this mismanagement, pharmaceutical R&D has become R&D in name only.

My own observations from working in the industry in a direct R&D support role tend to validate that description:

  • The budgets for informatics tools essential for R&D were controlled by non-scientists such as IT personnel with their own agendas, causing scientist to have to utilize extremely inefficient paper based information wasting much time, or avoid difficult and innovative research pursuits altogether.
  • Research support staff were micromanaged by non scientific superiors.
  • Scientist recruitment efforts were impaired by generic HR workers who served, in effect, as a barrier to creative talent not fitting the "judgment" of HR as a good fit (or whose defective eRecruiting systems rendered the CV of such people effectively invisible). Generic HR staff have no idea about who really is the best talent, as they (like many senior executives) lack the background to render such judgments. Talent often never gets seen by the hiring managers as a result.
  • Scientists were burdened with meetings, inundated with needless emails calling for equally unneeded information, requests for ill conceived "metrics" on productivity, and other petty tasks distracting them from actual scientific and intellectual focus.
  • Scientists were burdened with the time consuming bureaucratic insanity of developing yearly "management by objective" plans where they defined what they would accomplish for the year to then be evaluated upon (e.g., for bonuses), as if that were even possible and did not in effect create an atmosphere of "covertly lowered expectations." Scientists were also burdened by an increasing number of tedious and onerous HR processes for ongoing performance evaluation of themselves, their reports and their peers, again a distraction and disruption from scientific focus.
  • Scientists were forced to play nasty politics due to the pressures of constant downsizing, distracting them from useful work. At one pharma, for example, at times of downsizing scientists were made to "bid on their own jobs" as well as others, or face layoffs if no "match" was found. It was as if the company involved did not know what its people did, could do, and what it needed them to do. Nor did it seem to care that such a degrading process was anathema to innovative discovery.
  • Some VP or other executive comes up with some impractical if not crazy pet idea and puts scientists to work on it. The scientists know the idea is a bad one but are intimidated against speaking up lest they be "downsized" or otherwise penalized. Their time for more creative endeavors is thus wasted.

My colleagues in other pharmas describe similar circumstances.

A better description for what I describe above is perhaps the term coined by a correspondent, Felix Fulmer. He summarizes the situation as follows in this pithy and insightful statement:

What we today call pharmaceutical R&D is in reality busywork disguised to look like R&D, in effect a well engineered, well managed, massively expensive failure.

He opined that a small fraction of prime scientist intellectual horsepower and time is actually spent on true R&D, the rest wasted on feeding the bureaucratic corpulence that is the modern pharma research lab.

When you spend tens or hundreds of billions of dollars, you should have something to show for it if you are doing real research. The low hanging fruit haven't been that fully picked. That contention is supported by the accomplishments of the far less bureaucratic biotech and academic research sectors.

Today's Wall Street Journal editorial hit the nail on the head about the merger (my business-speak translations are in red italics):

The risk is that the cost savings [i.e., reduced personnel expenses gained by putting people out on the street -ed.] and bureaucratic mayhem from combining labs and streamlining R&D [cannibalizing good people -ed.] end up stifling research productivity [creativity - ed.]

Pfizer CEO Jeffrey Kindler is a lawyer [i.e., lacks biomedical and scientific education, experience and insight -ed.] who came to the drug giant from McDonald's [the hamburger joint - ed.] in 2006 and has been laying off scientific staff all over the place.

I had commented on Kindler's credentials in my July 2006 post "Pfizer brings life to my 'If you've run McDonald's, you can run anything' metaphor."

Merging with other companies and laying off scientific staff (instead of keeping them, hiring more of the best, and repairing the defective environment that distracts them from their work) is apparently the only "solution" that non biomedical business managers in this industry can proffer. They, like their impaired scientists, also suffer a lack of creativity in thought and application.

Through what magic is a merger between two companies that no longer know how to carry out effective R&D believed to work a miracle?

(Perhaps it is some form of ... management alchemy?)

Company growth depends on the new drug pipeline. Pipeline depends on R&D. R&D depends on leadership and research talent just as a good movie depends on both a good director and good acting. When both are lacking you cannot have growth, therefore why bother merging?

I simply do not see how shareholder value is created via this merger. I hold no stock nor financial interests nor relationships with either of these companies or any pharmas. I've chosen not to as a result of my observations from within the industry. It is also a fact that many if not most large mergers do not actually produce gains. I therefore suggest that individual and institutional investors and analysts take a bearish view of this merger.

Finally, the full page ad touting the merger mentioned at the beginning of this post ends as follows:

"The talented people we have the privilege of working with have a tireless commitment to improving the health of the patients we all serve. We look forward to working together to meaningfully advance our shared mission of applying innovative science to improve world health in the years to come." - Jeff Kindler, Pfizer Chairman and CEO, and Bernard Poussot, Wyeth Chairman, President and CEO

I guess the "talented people" and the "we" in the above self-aggrandizing passage doesn't include those scientists and other people who will find themselves on the street during the worst economic downturn since 1929.

As I observed in my July 2007 post "Happy Accidents in pharma doubtful: Tax Break Used by Drug Makers Failed to Add Jobs", the people who actually write this copy must understand the shallowness of their words.

Further, employees who read this rhetoric fall into one of two groups: those who believe it or are comforted by it, and thus are deluded, and those who don’t believe it, but cannot speak up due to fear of retaliation or layoff, and thus may easily become demoralized and cynical.

Environments of the deluded, demoralized and cynical are not the best for leading-edge drug R&D.

-- SS

Addendum Feb. 5:

Based on a Feb. 2 interview in Financial Times entitled "An Acute Talent for Innovation", Nobel prize winner and drug inventor Sir James Black would probably agree with many of the assessments above. I particularly like his recollection that:

Max Perutz, director of one of the most successful postwar science institutions, Cambridge University's Molecular Biology Laboratory, had compelling ideas on how best to nurture research, says Sir James: "No politics, no committees, no reports, no referees, no interviews - just highly motivated people picked by a few men of good judgment."


and his observation that:

There is no shortage of scientific talent, he says. "But [I am] much less optimistic about the managerial vision [of the pharmaceutical industry] to catalyse these talents to deliver the results we all want."


-- SS

At One Academic Medical Center: "Profitability" Trumps "Doing the Right Thing"

A post on the Health Care Blog opened a window into the thinking of top leaders of health care organizations. The post was written by Gary S Kaplan MD, the CEO of Virginia Mason Medical Center, a well reputed US academic medical center. It seemed generally well-intentioned, and was focused on the creation of an organization of US health care CEOs "dedicated to transforming health care and creating a more sustainable health system."

But my interest today is not this organization or its future plans.

Dr Kaplan's post included,

We, unfortunately, in the current payment system, reduce our profitability by doing the right thing. Despite my very supportive board of directors, they will not allow me to lead our organization into bankruptcy by doing the right thing. We need to change our payment system if we truly want to ensure universal coverage, improve quality and reduce cost.


I completely agree with Dr Kaplan about the need to change how we pay doctors and hospitals. But note his second sentence.

It implies that the leadership of Virginia Mason sees "profitability" as a goal of the organization that supersedes "doing the right thing." Furthermore, Dr Kaplan implies that his medical center's board of directors has prevented him from "doing the right thing," in order to avoid "bankruptcy."

Perhaps this was just a horribly written paragraph. But it does seem to say that at Virginia Mason Medical Center, the leadership thinks it is less important to uphold the organization's mission, that is, to do "the right thing," and more important to promote "profitability."

However, Virginia Mason Medical Center is a not-for-profit organization. (See this link.) A not-for-profit organization should not have "profitability," by definition.

Furthermore, the leadership of a not-for-profit organization is supposed to uphold the organization's mission, and to put this mission ahead of other concerns. This is called the duty of obedience, and is a fundamental duty of leaders of not-for-profit organizations (see this link). Failure to uphold the mission threatens the fundamental integrity of the organization.

Naturally, to fulfill the mission, the leadership of a not-for-profit should not let the organization go bankrupt. It should be concerned about raising and having sufficient funds to make an honest attempt to fulfill the mission. But bringing in money should be secondary to the mission, and "profitability" should not be a goal.

By the way, the current stated mission of Virginia Mason Medical Center is:


Our vision is to be the Quality Leader - Our aspiration is not to be the biggest, but to be the best. We will differentiate ourselves on the basis of quality.

Our mission is to improve the health and well being of the patients we serve - Healing illness is our first priority and is what gives our people the energy for our vision. We are also committed to providing a broad range of services that improve one's sense of well-being and which prevent illness.

We have previously discussed how a leader of another not-for-profit academic medical center revealed that his major criterion for evaluating faculty members was how much money they brought in, not how well they fulfilled their academic and clinical responsibilities. His goal was to make sure enough faculty were "taxpayers," people who brought in more money than they consumed (not that enough faculty were good clinicians, teachers, or researchers.) Again, it seemed that his organization put making money ahead of fulfilling its mission, ignoring their duty of obedience.

Now apparently another leader of a not-for-profit academic medical center has let slip that the leadership of his organization is thinking the same way, but on a more macro level.

By the way, I doubt that the thinking disclosed by these two leaders is anomalous. What is anomalous is that they made it public. Many academic medical institutions could be lead by people who put profits ahead of mission, thus shirking the duty of obedience, and hollowing out the integrity of their institutions.

Academic medical institutions, like most health care institutions, are now lead by business people who grew up in what now appears to have been the second gilded age. The global economic meltdown has made it clear that we just lived through an era in which business leadership was too often marked by arrogance, greed and corruption. Business leaders took ridiculous risks, deceptively marketed products, and manipulated financial instruments to generate short-term profits, and thus to generate fabulous payments to those same leaders. And we have seen how these practices nearly destroyed the global financial system and have lead the world to the brink of a new great depression.

At least the global financial meltdown has discredited the notion that markets not subject to any external regulation or policing will somehow police themselves. So maybe it is time to add a little regulation and policing to health care. One place to start would be the duties of the leaders of not-for-profit health care organizations.

These include
  • the duty of obedience: they need to put their organizations' missions ahead of other concerns.
  • the duty of loyalty: they need to give their organizations their undivided allegiance when making decisions.
  • the duty of care: they need to exercise reasonable care when making decisions.

But as long as the leaders of not-for-profit health care organizations continue to put profitability ahead of mission, things will continue to get worse.

BLOGSCAN - Whose Interests Do Medical Societies Promote?

On the Alison Bass blog, Alison Bass (no surprise) wrote about an important topic that needs more discussion. It turns out that several big medical societies recently threatened to pull their meetings out of Massachusetts ostensibly because of concerns that a new state law regulating drug and device marketing would make it impossible to hold the meetings. Ms Bass is skeptical about that claim, but did note that the medical societies got funding from drug or device companies, companies that are generally not happy with any laws that restrict their marketing practices, or make these practices more transparent. The important topic here is how medical societies, which once we thought were meant to promote doctors' ideals (and to be honest, their interests), now seem to be creatures of drug, biotechnology, and device companies, to the detriment of doctors' ideals and interests.

Vitamin K2 and Cranial Development

One of the things Dr. Weston Price noticed about healthy traditional cultures worldwide is their characteristically broad faces, broad dental arches and wide nostrils. Due to the breadth of their dental arches, they invariably had straight teeth and enough room for wisdom teeth. As soon as these same groups adopted white flour and sugar, the next generation to be born grew up with narrow faces, narrow dental arches, crowded teeth, pinched nostrils and a characteristic underdevelopment of the middle third of the face.

Here's an excerpt from Nutrition and Physical Degeneration, about traditional and modernized Swiss groups. Keep in mind these are Europeans we're talking about (although he found the same thing in all the races he studied):
The reader will scarcely believe it possible that such marked differences in facial form, in the shape of the dental arches, and in the health condition of the teeth as are to be noted when passing from the highly modernized lower valleys and plains country in Switzerland to the isolated high valleys can exist. Fig. 3 shows four girls with typically broad dental arches and regular arrangement of the teeth. They have been born and raised in the Loetschental Valley or other isolated valleys of Switzerland which provide the excellent nutrition that we have been reviewing.

Another change that is seen in passing from the isolated groups with their more nearly normal facial developments, to the groups of the lower valleys, is the marked irregularity of the teeth with narrowing of the arches and other facial features... While in the isolated groups not a single case of a typical mouth breather was found, many were seen among the children of the lower-plains group. The children studied were from ten to sixteen years of age.
Price attributed this physical change to a lack of minerals and the fat-soluble vitamins necessary to make good use of them: vitamin A, vitamin D and what he called "activator X"-- now known to be vitamin K2 MK-4. The healthy cultures he studied all had an adequate source of vitamin K2, but many ate very little K1 (which comes mostly from vegetables). Inhabitants of the Loetschental valley ate green vegetables only in summer, due to the valley's harsh climate. The rest of the year, the diet was limited chiefly to whole grain sourdough rye bread and pastured dairy products.

The dietary transitions Price observed were typically from mineral- and vitamin-rich whole foods to refined modern foods, predominantly white flour and sugar. The villagers of the Loetschental valley obtained their fat-soluble vitamins from pastured dairy, which is particularly rich in vitamin K2 MK-4.

In a modern society like the U.S., most people exhibit signs of poor cranial development. How many people do you know with perfectly straight teeth who never required braces? How many people do you know whose wisdom teeth erupted normally?

The archaeological record shows that our hunter-gatherer ancestors generally didn't have crooked teeth. Humans evolved to have dental arches in proportion to their tooth size, like all animals. Take a look at these chompers. That skull is from an archaeological site in the Sahara desert that predates agriculture in the region. Those beautiful teeth are typical of paleolithic humans and modern hunter-gatherers. Crooked teeth and impacted wisdom teeth are only as old as agriculture. However, Price found that with care, certain traditional cultures were able to build well-formed skulls on an agricultural diet.

So was Price on to something, or was he just cherry picking individuals that supported his hypothesis? It turns out there's a developmental syndrome in the literature that might shed some light on this. It's called Binder's syndrome. Here's a description from a review paper about Binder's syndrome (emphasis mine):

The essential features of maxillo-nasal dysplasia were initially described by Noyes in 1939, although it was Binder who first defined it as a distinct clinical syndrome. He reported on three cases and recorded six specific characteristics:5

  • Arhinoid face.
  • Abnormal position of nasal bones.
  • Inter-maxillary hypoplasia with associated malocclusion.
  • Reduced or absent anterior nasal spine.
  • Atrophy of nasal mucosa.
  • Absence of frontal sinus (not obligatory).
Individuals with Binder's syndrome have a characteristic appearance that is easily recognizable.6 The mid-face profile is hypoplastic, the nose is flattened, the upper lip is convex with a broad philtrum, the nostrils are typically crescent or semi-lunar in shape due to the short collumela, and a deep fold or fossa occurs between the upper lip and the nose, resulting in an acute nasolabial angle.
Allow me to translate: in Binder's patients, the middle third of the face is underdeveloped, they have narrow dental arches and crowded teeth, small nostrils and abnormally small sinuses (sometimes resulting in mouth breathing). Sound familiar? So what causes Binder's syndrome? I'll give you a hint: it can be caused by prenatal exposure to warfarin (coumadin).

Warfarin is rat poison. It kills rats by causing them to lose their ability to form blood clots, resulting in massive hemmorhage. It does this by depleting vitamin K, which is necessary for the proper functioning of blood clotting factors. It's used (in small doses) in humans to thin the blood as a treatment for abnormal blood clots. As it turns out, Binder's syndrome can be caused by
a number of things that interfere with vitamin K metabolism. The sensitive period for humans is the first trimester. I think we're getting warmer...

Another name for Binder's syndrome is "warfarin embryopathy". There happens to be
a rat model of it. Dr. Bill Webster's group at the University of Sydney injected rats daily with warfarin for up to 12 weeks, beginning on the day they were born (rats have a different developmental timeline than humans). They also administered large doses of vitamin K1 along with it. This is to ensure the rats continue to clot normally, rather than hemorrhaging. Another notable property of warfarin that I've mentioned before is its ability to inhibit the conversion of vitamin K1 to vitamin K2 MK-4. Here's what they had to say about the rats:
The warfarin-treated rats developed a marked maxillonasal hypoplasia associated with a 11-13% reduction in the length of the nasal bones compared with controls... It is proposed that (1) the facial features of the human warfarin embryopathy are caused by reduced growth of the embryonic nasal septum, and (2) the septal growth retardation occurs because the warfarin-induced extrahepatic vitamin K deficiency prevents the normal formation of the vitamin K-dependent matrix gla protein in the embryo.
"Maxillonasal hypoplasia" means underdevelopment of the jaws and nasal region. Proper development of this region requires fully active matrix gla protein (MGP), which I've written about before in the context of vascular calcification. MGP requires vitamin K to activate it, and it seems to prefer K2 MK-4 to K1, at least in the vasculature. Administering K2 MK-4 along with warfarin prevents warfarin's ability to cause arterial calcification (thought to be an MGP-dependent mechanism), whereas administering K1 does not.

Here are a few quotes from a review paper by Dr. Webster's group. I have to post the whole abstract because it's a gem:
The normal vitamin K status of the human embryo appears to be close to deficiency [I would argue in most cases the embryo is actually deficient, as are most adults in industrial societies]. Maternal dietary deficiency or use of a number of therapeutic drugs during pregnancy, may result in frank vitamin K deficiency in the embryo. First trimester deficiency results in maxillonasal hypoplasia in the neonate with subsequent facial and orthodontic implications. A rat model of the vitamin K deficiency embryopathy shows that the facial dysmorphology is preceded by uncontrolled calcification in the normally uncalcified nasal septal cartilage, and decreased longitudinal growth of the cartilage, resulting in maxillonasal hypoplasia. The developing septal cartilage is normally rich in the vitamin K-dependent protein matrix gla protein (MGP). It is proposed that functional MGP is necessary to maintain growing cartilage in a non-calcified state. Developing teeth contain both MGP and a second vitamin K-dependent protein, bone gla protein (BGP). It has been postulated that these proteins have a functional role in tooth mineralization. As yet this function has not been established and abnormalities in tooth formation have not been observed under conditions where BGP and MGP should be formed in a non-functional form.
I think there's a good case to be made that most people in modern societies exhibit some degree of "Binder's syndrome" due to subclinical vitamin K2 deficiency during growth. I believe the evidence suggests that prenatal vitamin K2 MK-4 deficiency is behind narrow dental arches, crooked teeth, underdevelopment of the face and jaw, underdevelopment of the sinuses with mouth breathing in some cases, and poor tooth development resulting in a high susceptibility to dental cavities.

These symptoms are so common they are viewed as normal in industrial societies. There is no other single factor that so elegantly explains these characteristic changes in cranial form.
Rickets (vitamin D deficiency during growth) also causes cranial malformations, but they are distinct from those caused by K2 deficiency.

Humans do not efficiently convert K1 into K2 MK-4 (unlike rats), so we require a ready source of K2 in the diet. Our hunter-gatherer ancestors had a relatively high intake of K2 MK-4 from the organs of wild animals (particularly brain, pancreas, and marrow), insects and seafood. Our food supply today is depleted of K2, due to our avoidance of organ meats and poor animal husbandry practices. K2 MK-4 is found only in animal products. Pastured dairy is the most convenient source of K2 MK-4 in the modern diet, just as it was for the villagers of the Loetschental valley when Dr. Price visited them. Dairy from grain-fed cows contains much less K2.


Price felt that to ensure the proper development of their children, mothers should eat a diet rich in fat-soluble vitamins both before and during pregnancy. This makes sense in light of what we now know. There is a pool of vitamin K2 MK-4 in the organs that turns over very slowly, in addition to a pool in the blood that turns over rapidly. Entering pregnancy with a full store means a greater chance of having enough of the vitamin for the growing fetus. Healthy traditional cultures often fed special foods rich in fat-soluble vitamins to women of childbearing age and expectant mothers, thus ensuring beautiful and robust progeny.


Vitamin K2 and Cranial Development

One of the things Dr. Weston Price noticed about healthy traditional cultures worldwide is their characteristically broad faces, broad dental arches and wide nostrils. Due to the breadth of their dental arches, they invariably had straight teeth and enough room for wisdom teeth. As soon as these same groups adopted white flour and sugar, the next generation to be born grew up with narrow faces, narrow dental arches, crowded teeth, pinched nostrils and a characteristic underdevelopment of the middle third of the face.

Here's an excerpt from Nutrition and Physical Degeneration, about traditional and modernized Swiss groups. Keep in mind these are Europeans we're talking about (although he found the same thing in all the races he studied):
The reader will scarcely believe it possible that such marked differences in facial form, in the shape of the dental arches, and in the health condition of the teeth as are to be noted when passing from the highly modernized lower valleys and plains country in Switzerland to the isolated high valleys can exist. Fig. 3 shows four girls with typically broad dental arches and regular arrangement of the teeth. They have been born and raised in the Loetschental Valley or other isolated valleys of Switzerland which provide the excellent nutrition that we have been reviewing.

Another change that is seen in passing from the isolated groups with their more nearly normal facial developments, to the groups of the lower valleys, is the marked irregularity of the teeth with narrowing of the arches and other facial features... While in the isolated groups not a single case of a typical mouth breather was found, many were seen among the children of the lower-plains group. The children studied were from ten to sixteen years of age.
Price attributed this physical change to a lack of minerals and the fat-soluble vitamins necessary to make good use of them: vitamin A, vitamin D and what he called "activator X"-- now known to be vitamin K2 MK-4. The healthy cultures he studied all had an adequate source of vitamin K2, but many ate very little K1 (which comes mostly from vegetables). Inhabitants of the Loetschental valley ate green vegetables only in summer, due to the valley's harsh climate. The rest of the year, the diet was limited chiefly to whole grain sourdough rye bread and pastured dairy products.

The dietary transitions Price observed were typically from mineral- and vitamin-rich whole foods to refined modern foods, predominantly white flour and sugar. The villagers of the Loetschental valley obtained their fat-soluble vitamins from pastured dairy, which is particularly rich in vitamin K2 MK-4.

In a modern society like the U.S., most people exhibit signs of poor cranial development. How many people do you know with perfectly straight teeth who never required braces? How many people do you know whose wisdom teeth erupted normally?

The archaeological record shows that our hunter-gatherer ancestors generally didn't have crooked teeth. Humans evolved to have dental arches in proportion to their tooth size, like all animals. Take a look at these chompers. That skull is from an archaeological site in the Sahara desert that predates agriculture in the region. Those beautiful teeth are typical of paleolithic humans and modern hunter-gatherers. Crooked teeth and impacted wisdom teeth are only as old as agriculture. However, Price found that with care, certain traditional cultures were able to build well-formed skulls on an agricultural diet.

So was Price on to something, or was he just cherry picking individuals that supported his hypothesis? It turns out there's a developmental syndrome in the literature that might shed some light on this. It's called Binder's syndrome. Here's a description from a review paper about Binder's syndrome (emphasis mine):

The essential features of maxillo-nasal dysplasia were initially described by Noyes in 1939, although it was Binder who first defined it as a distinct clinical syndrome. He reported on three cases and recorded six specific characteristics:5

  • Arhinoid face.
  • Abnormal position of nasal bones.
  • Inter-maxillary hypoplasia with associated malocclusion.
  • Reduced or absent anterior nasal spine.
  • Atrophy of nasal mucosa.
  • Absence of frontal sinus (not obligatory).
Individuals with Binder's syndrome have a characteristic appearance that is easily recognizable.6 The mid-face profile is hypoplastic, the nose is flattened, the upper lip is convex with a broad philtrum, the nostrils are typically crescent or semi-lunar in shape due to the short collumela, and a deep fold or fossa occurs between the upper lip and the nose, resulting in an acute nasolabial angle.
Allow me to translate: in Binder's patients, the middle third of the face is underdeveloped, they have narrow dental arches and crowded teeth, small nostrils and abnormally small sinuses (sometimes resulting in mouth breathing). Sound familiar? So what causes Binder's syndrome? I'll give you a hint: it can be caused by prenatal exposure to warfarin (coumadin).

Warfarin is rat poison. It kills rats by causing them to lose their ability to form blood clots, resulting in massive hemmorhage. It does this by depleting vitamin K, which is necessary for the proper functioning of blood clotting factors. It's used (in small doses) in humans to thin the blood as a treatment for abnormal blood clots. As it turns out, Binder's syndrome can be caused by
a number of things that interfere with vitamin K metabolism. The sensitive period for humans is the first trimester. I think we're getting warmer...

Another name for Binder's syndrome is "warfarin embryopathy". There happens to be
a rat model of it. Dr. Bill Webster's group at the University of Sydney injected rats daily with warfarin for up to 12 weeks, beginning on the day they were born (rats have a different developmental timeline than humans). They also administered large doses of vitamin K1 along with it. This is to ensure the rats continue to clot normally, rather than hemorrhaging. Another notable property of warfarin that I've mentioned before is its ability to inhibit the conversion of vitamin K1 to vitamin K2 MK-4. Here's what they had to say about the rats:
The warfarin-treated rats developed a marked maxillonasal hypoplasia associated with a 11-13% reduction in the length of the nasal bones compared with controls... It is proposed that (1) the facial features of the human warfarin embryopathy are caused by reduced growth of the embryonic nasal septum, and (2) the septal growth retardation occurs because the warfarin-induced extrahepatic vitamin K deficiency prevents the normal formation of the vitamin K-dependent matrix gla protein in the embryo.
"Maxillonasal hypoplasia" means underdevelopment of the jaws and nasal region. Proper development of this region requires fully active matrix gla protein (MGP), which I've written about before in the context of vascular calcification. MGP requires vitamin K to activate it, and it seems to prefer K2 MK-4 to K1, at least in the vasculature. Administering K2 MK-4 along with warfarin prevents warfarin's ability to cause arterial calcification (thought to be an MGP-dependent mechanism), whereas administering K1 does not.

Here are a few quotes from a review paper by Dr. Webster's group. I have to post the whole abstract because it's a gem:
The normal vitamin K status of the human embryo appears to be close to deficiency [I would argue in most cases the embryo is actually deficient, as are most adults in industrial societies]. Maternal dietary deficiency or use of a number of therapeutic drugs during pregnancy, may result in frank vitamin K deficiency in the embryo. First trimester deficiency results in maxillonasal hypoplasia in the neonate with subsequent facial and orthodontic implications. A rat model of the vitamin K deficiency embryopathy shows that the facial dysmorphology is preceded by uncontrolled calcification in the normally uncalcified nasal septal cartilage, and decreased longitudinal growth of the cartilage, resulting in maxillonasal hypoplasia. The developing septal cartilage is normally rich in the vitamin K-dependent protein matrix gla protein (MGP). It is proposed that functional MGP is necessary to maintain growing cartilage in a non-calcified state. Developing teeth contain both MGP and a second vitamin K-dependent protein, bone gla protein (BGP). It has been postulated that these proteins have a functional role in tooth mineralization. As yet this function has not been established and abnormalities in tooth formation have not been observed under conditions where BGP and MGP should be formed in a non-functional form.
I think there's a good case to be made that most people in modern societies exhibit some degree of "Binder's syndrome" due to subclinical vitamin K2 deficiency during growth. I believe the evidence suggests that prenatal vitamin K2 MK-4 deficiency is behind narrow dental arches, crooked teeth, underdevelopment of the face and jaw, underdevelopment of the sinuses with mouth breathing in some cases, and poor tooth development resulting in a high susceptibility to dental cavities.

These symptoms are so common they are viewed as normal in industrial societies. There is no other single factor that so elegantly explains these characteristic changes in cranial form.
Rickets (vitamin D deficiency during growth) also causes cranial malformations, but they are distinct from those caused by K2 deficiency.

Humans do not efficiently convert K1 into K2 MK-4 (unlike rats), so we require a ready source of K2 in the diet. Our hunter-gatherer ancestors had a relatively high intake of K2 MK-4 from the organs of wild animals (particularly brain, pancreas, and marrow), insects and seafood. Our food supply today is depleted of K2, due to our avoidance of organ meats and poor animal husbandry practices. K2 MK-4 is found only in animal products. Pastured dairy is the most convenient source of K2 MK-4 in the modern diet, just as it was for the villagers of the Loetschental valley when Dr. Price visited them. Dairy from grain-fed cows contains much less K2.


Price felt that to ensure the proper development of their children, mothers should eat a diet rich in fat-soluble vitamins both before and during pregnancy. This makes sense in light of what we now know. There is a pool of vitamin K2 MK-4 in the organs that turns over very slowly, in addition to a pool in the blood that turns over rapidly. Entering pregnancy with a full store means a greater chance of having enough of the vitamin for the growing fetus. Healthy traditional cultures often fed special foods rich in fat-soluble vitamins to women of childbearing age and expectant mothers, thus ensuring beautiful and robust progeny.


BLOGSCAN - How US Medicare Will Pay for Cancer Drugs

On the GoozNews blog, Merrill Goozner dissects the recent decision by the US Center for Medicare and Medicaid Services (CMS) to make more lenient the criteria it uses to decide which off-label anti-cancer drugs it will pay for. Now any drug rated favorably in at least one of several drug compendia will be approved. Yet it turns out that intricate, but important conflicts of interest may affect how drugs get positive reviews in some of the compendia. It does seem that nearly every piece of our fiendishly complex health care system is affected by conflicts of interest. To put the most positive interpretation on it, most US government agencies that deal with health care seem to have operated up to now in ignorant bliss when it comes to these conflicts.

NB: see also the post by Dr Howard Brody on the Hooked: Ethics, Medicine and Pharma blog, and the links he provides.

Paying More for Worse Outcomes - the Wyeth/ DesignWrite/ University of Wisconsin Hormone Replacement Therapy Course as Microcosm

The Milwaukee Journal-Sentinel just published a remarkable investigative report about continuing medical education courses provided (after a fashion) by the University of Wisconsin. Here are the main points,

The course was created by a medical education and communications company (MECC), paid for by Wyeth


The course material was developed largely by DesignWrite, a New Jersey-based firm paid by Wyeth.

The company is being investigated along with Wyeth by a U.S. senator looking into the practice of ghostwriting in scientific articles as a way to market hormone therapy drugs.

Together, Wyeth, DesignWrite and UW formed the Council on Hormone Education - the name of the educational organization stamped on course material for the class.

Thirty-four of the 40 council member physicians have financial ties to Wyeth, including the course director, Julie Fagan, a UW doctor and associate professor of medicine.


The course put hormone replacement therapy (HRT) for post-menopausal women in a very favorable light, at a time when results from a prominent randomized controlled trial sponsored by the Womens Health Initiative (WHI) had just become available, suggesting that HRT does more harm than good:


Rigorous studies involving thousands of women showed that hormone therapy increases the risk of heart disease, stroke, breast cancer, blood clots and dementia. They also showed quality-of-life benefits are short-lived.

In May 2002, a major clinical trial that was part of the Women's Health Initiative was suspended because medical investigators were worried they were subjecting women to too much risk.

In the fall of 2002, just months after the health initiative was stopped, the Council on Hormone Education launched its first UW hormone therapy medical education course.

'There were millions of women impacted by that information, and physicians and women really needed to have that information,' said Doug Petkus, spokesman for Wyeth. 'We felt we were providing a service to them by helping them . . . understand the significance.'

Over the next several years, Wyeth poured $12 million into the course.

According to the first newsletter published by the Council on Hormone Education, the goal of the course was 'to develop and disseminate balanced, accurate, timely and consistent information about hormone therapy' so doctors could "better serve women."

Other newsletters, which included patient handouts and multiple-choice exams in the back for physicians, urged doctors to consider the bonuses of hormone therapy.

For instance, in a newsletter titled 'Menopause and Quality of Life,' Wyeth-funded researcher JoAnn Pinkerton wrote: 'Undesirable skin changes associated with aging can have a deleterious impact on both physical and mental health. These changes include lines, wrinkles and dryness that affect Quality of Life.'

'American women attach to youthful, attractive skin,' she wrote, explaining that the age-induced changes are in large part the result of estrogen loss. There is no scientific consensus that estrogen supplements will reverse the aging process in skin.

The University of Virginia Health System doctor also suggested that depression, insomnia and mood issues could be the result of estrogen and other hormone imbalances.

Her conclusion: 'Hormone therapy treats menopausal symptoms more effectively than any other single agent.' And a physician must weigh those benefits against a woman's risk for 'coronary heart disease, deep vein thrombosis, pulmonary embolism, stroke, breast cancer, and gall bladder problems, which hormone therapy may be associated with.'

Fagan, the UW course director, defended the program, saying nothing in the course material was scientifically inaccurate. However, she said the material was presented in a 'more positive light' than she would have preferred.

Some experts who reviewed the material thought that the "positive light" it placed on hormone replacement was very bright.

The Journal Sentinel asked several doctors, including Jacques Rossouw, chief of the Women's Health Initiative branch of the National Institutes of Health, to review course material. The initiative is the largest clinical trial of hormone therapy drugs.

He said the views expressed in the course are not those of the general scientific community and are not suitable for a university medical education course.

'There is a history of this kind of thing from Wyeth,' Rossouw said. 'The materials regurgitate lines that I have heard and read many times, and I have come to believe (though I do not know) that this is part of an overall marketing strategy to the profession. It is not good science because it fails to strive for any kind of balance.'

Raymond Gibbons, a professor of medicine at the Mayo Clinic and former president of the American Heart Association, said he also found material relating to heart disease one-sided.

He noted that the materials inappropriately gave observational data equal weight to rigorously done, randomized clinical trials.

'It's a lot of post hoc analysis,' he said. 'I don't see the other side of the argument.'

This is the second time that the University of Wisconsin medical school has received media attention for the cozy relationships with industry enjoyed by the school and its faculty members. We posted about some University of Wisconsin faculty's lucrative industry relationships, which they often did not fully disclose.

This, of course, is another story about how the web of conflicts of interest that now so enmesh academic medicine can enable stealth marketing, the disguising of marketing of commercial health care goods or services as medical education.

But because of the timing and subject matter of this course, this case has become a microcosm of much of what has gone wrong with US (and global) health care. Note this progression:

- Wyeth paid DesignWrite to design the course, which then paid the University of Wisconsin and its faculty to produce it. Thus considerable money flowed to the MECC and its employees, and to the university and its faculty. Ultimately, this came out of the pockets of patients or the public, adding to health care costs.
- The course they produced was viewed by numerous physicians. It is likely at least some were influenced by it to prescribe long-term HRT.
- Yet there is now (and there was in 2002) reason to believe that long-term HRT does more harm than good. A review in 2002 (see this link for summary, and links to the review) suggested that it produces increased risks of breast cancer, stroke, and pulmonary embolism which outweigh decreses in colorectal cancer and fracture. The WHI trial in JAMA had similar results (link here.)
- Therefore, more patients prescribed HRT by these physicians may have been harmed by it than were helped. Thus, the course not only added to health care costs, but likely worsened health care outcomes.

So in this case, deceptive practices presumably condoned by the leadership of a drug company, by the leadership of an academic medical institution, and by particular medical faculty, all of whom may have benefited personally by money spent to conduct these practices, likely did patients no good, and possibly did them serious harm. Deceptive practices and conflicts of interest resulted in increased health care costs and probably worse health care outcomes.

This suggests, as we have said before, that bad leadership of health care organizations causes these organizations to employ ethically questionable tactics, and these tactics in turn can systemically increase costs and worsen outcomes.

But up to now, there has been little public discussion of bad leadership and governance of health care organizations, the unethical tactics that bad leaders may employ, and how these tactics threaten physicians' professional values, and lead to bad outcomes for patients and society. Up to now, those interested in health care policy and health systems research have ignored these issues, which appear to be the herd of elephants in the health care living room.

But maybe if we improved the leadership and governance of health care organizations, and prevented the unethical practices they may employ, we could improve patient outcomes while actually controlling costs, improving access, and improving professional morale.

Of course, doing so would threaten many vested interests and fat wallets.

See also Dr Daniel Carlat's comments on the Carlat Psychiatry Blog, and Margaret Soltan's comments on University Diaries. Hat tip to PharmaGossip and the Schwitzer Health News blog.

The Tokelau Island Migrant Study: The Final Word

Over the course of the last month, I've outlined some of the major findings of the Tokelau Island Migrant study. It's one of the most comprehensive studies I've found of a traditional culture transitioning to a modern diet and lifestyle. It traces the health of the inhabitants of the Pacific island Tokelau over time, as well as the health of Tokelauan migrants to New Zealand.

Unfortunately, the study began after the introduction of modern foods. We will never know for sure what Tokelauan health was like when their diet was completely traditional. To get some idea, we have to look at other traditional Pacific islanders such as the Kitavans.

What we can say is that an increase in the consumption of modern foods on Tokelau, chiefly white wheat flour and refined sugar, correlated with an increase in several non-communicable disorders, including overweight, diabetes and severe tooth decay. Further modernization as Tokelauans migrated to New Zealand corresponded with an increase in nearly every disorder measured, including heart disease, weight gain, diabetes, asthma and gout. These are all "diseases of civilization", which are not observed in hunter-gatherers and certain non-industrial populations throughout the world.

One of the most interesting things about Tokelauans is their extreme saturated fat intake, 40- 50% of calories. That's more than any other population I'm aware of. Yet Tokelauans appear to have a low incidence of heart attacks, lower than their New Zealand- dwelling relatives who eat half as much saturated fat. This should not be buried in the scientific literature; it should be common knowledge.

Overall, I believe the Tokelau Island Migrant study (among others) shows us that partially replacing nourishing traditional foods with modern foods such as processed wheat and sugar, is enough to cause a broad range of disorders not seen in hunter-gatherers but typical of modern societies. Changes in vitamin D status between Tokelau and New Zealand may have also played a role, due to the more indoor lifestyle of migrants.

The Tokelau Island Migrant Study: Background and Overview
The Tokelau Island Migrant Study: Dental Health
The Tokelau Island Migrant Study: Cholesterol and Cardiovascular Health
The Tokelau Island Migrant Study: Weight Gain
The Tokelau Island Migrant Study: Diabetes
The Tokelau Island Migrant Study: Asthma

The Tokelau Island Migrant Study: The Final Word

Over the course of the last month, I've outlined some of the major findings of the Tokelau Island Migrant study. It's one of the most comprehensive studies I've found of a traditional culture transitioning to a modern diet and lifestyle. It traces the health of the inhabitants of the Pacific island Tokelau over time, as well as the health of Tokelauan migrants to New Zealand.

Unfortunately, the study began after the introduction of modern foods. We will never know for sure what Tokelauan health was like when their diet was completely traditional. To get some idea, we have to look at other traditional Pacific islanders such as the Kitavans.

What we can say is that an increase in the consumption of modern foods on Tokelau, chiefly white wheat flour and refined sugar, correlated with an increase in several non-communicable disorders, including overweight, diabetes and severe tooth decay. Further modernization as Tokelauans migrated to New Zealand corresponded with an increase in nearly every disorder measured, including heart disease, weight gain, diabetes, asthma and gout. These are all "diseases of civilization", which are not observed in hunter-gatherers and certain non-industrial populations throughout the world.

One of the most interesting things about Tokelauans is their extreme saturated fat intake, 40- 50% of calories. That's more than any other population I'm aware of. Yet Tokelauans appear to have a low incidence of heart attacks, lower than their New Zealand- dwelling relatives who eat half as much saturated fat. This should not be buried in the scientific literature; it should be common knowledge.

Overall, I believe the Tokelau Island Migrant study (among others) shows us that partially replacing nourishing traditional foods with modern foods such as processed wheat and sugar, is enough to cause a broad range of disorders not seen in hunter-gatherers but typical of modern societies. Changes in vitamin D status between Tokelau and New Zealand may have also played a role, due to the more indoor lifestyle of migrants.

The Tokelau Island Migrant Study: Background and Overview
The Tokelau Island Migrant Study: Dental Health
The Tokelau Island Migrant Study: Cholesterol and Cardiovascular Health
The Tokelau Island Migrant Study: Weight Gain
The Tokelau Island Migrant Study: Diabetes
The Tokelau Island Migrant Study: Asthma

The Tokelau Island Migrant Study: Gout

Gout is a disorder in which uric acid crystals form in the joints, causing intense pain. The body forms uric acid as a by-product of purine metabolism. Purines are a building block of DNA, among other things. Uric acid is normally excreted into the urine, hence the name.

On Tokelau between 1971 and 1982, gout prevalence fell slightly. In migrants to New Zealand, gout prevalence began at the same level as on Tokelau but increased rapidly over the same time period. Here are the prevalence data for men, from Migration and Health in a Small Society: the Case of Tokelau (I don't have data for women):

This paper found that the age-standardized risk of developing gout was 9 times higher in New Zealand than on Tokelau for men, and 2.7 times higher for women.

Gout is usually treated by taking drugs and avoiding purine-rich foods. According to Wikipedia's entry on purines, these include:
sweetbreads [calf thymus or pancreas], anchovies, sardines, liver, beef kidneys, brains, meat extracts (e.g Oxo, Bovril), herring, mackerel, scallops, game meats, and gravy. A moderate amount of purine is also contained in beef, pork, poultry, fish and seafood, asparagus, cauliflower, spinach, mushrooms, green peas, lentils, dried peas, beans, oatmeal, wheat bran and wheat germ.
Those include some of the most nutritious foods available! The idea that the human body would not have evolved to tolerate most of the foods listed above is beyond comprehension, given our species' carnivorous tendencies. As a matter of fact, the only controlled trial I found suggests that a diet high in purines from animal protein has no effect on the uric acid concentration in the blood, because the body simply excretes any excess. In any case, like cholesterol, the majority of purines in the body are synthesized on-site, rather than coming from the diet. The only thing I found in support of the purine-gout hypothesis was a prospective study from 2004 that found an association between dietary purines and gout. I think we need to consider other possibilities.

Is there anything else that elevates uric acid in humans? Ah, sugar, one of my favorite punching bags. You never let me down, old friend. Refined sugar (sucrose) increases serum uric acid under controlled conditions, as does fructose when compared to starch. This has never been demonstrated for purine-rich foods that I could find.

Another clue comes from a disorder called "hereditary fructose intolerance". These patients are missing an enzyme required for metabolizing fructose, and must avoid it or risk becoming very ill. Some of the relatives of these patients are "heterozygous" for the mutation, meaning they have one mutated copy of the gene and one normal copy. They can metabolize fructose, but at a slower rate than someone with two functional copies. And they also have a very high incidence of gout.

Tokelauan migrants to New Zealand consumed significantly more sugar than Tokelauans on Tokelau during this study period (13 vs. 8 percent of calories in 1982). This explanation makes much more sense to me than the idea that gout is caused by the very foods that have sustained us as long as our species has existed.

There is one piece that doesn't fit, however. If sugar is causing gout, then why didn't gout incidence increase on Tokelau as their sugar consumption increased? I don't know. Perhaps there is another factor involved as well. Any thoughts?

The Tokelau Island Migrant Study: Background and Overview
The Tokelau Island Migrant Study: Dental Health
The Tokelau Island Migrant Study: Cholesterol and Cardiovascular Health
The Tokelau Island Migrant Study: Weight Gain
The Tokelau Island Migrant Study: Diabetes
The Tokelau Island Migrant Study: Asthma

The Tokelau Island Migrant Study: Gout

Gout is a disorder in which uric acid crystals form in the joints, causing intense pain. The body forms uric acid as a by-product of purine metabolism. Purines are a building block of DNA, among other things. Uric acid is normally excreted into the urine, hence the name.

On Tokelau between 1971 and 1982, gout prevalence fell slightly. In migrants to New Zealand, gout prevalence began at the same level as on Tokelau but increased rapidly over the same time period. Here are the prevalence data for men, from Migration and Health in a Small Society: the Case of Tokelau (I don't have data for women):

This paper found that the age-standardized risk of developing gout was 9 times higher in New Zealand than on Tokelau for men, and 2.7 times higher for women.

Gout is usually treated by taking drugs and avoiding purine-rich foods. According to Wikipedia's entry on purines, these include:
sweetbreads [calf thymus or pancreas], anchovies, sardines, liver, beef kidneys, brains, meat extracts (e.g Oxo, Bovril), herring, mackerel, scallops, game meats, and gravy. A moderate amount of purine is also contained in beef, pork, poultry, fish and seafood, asparagus, cauliflower, spinach, mushrooms, green peas, lentils, dried peas, beans, oatmeal, wheat bran and wheat germ.
Those include some of the most nutritious foods available! The idea that the human body would not have evolved to tolerate most of the foods listed above is beyond comprehension, given our species' carnivorous tendencies. As a matter of fact, the only controlled trial I found suggests that a diet high in purines from animal protein has no effect on the uric acid concentration in the blood, because the body simply excretes any excess. In any case, like cholesterol, the majority of purines in the body are synthesized on-site, rather than coming from the diet. The only thing I found in support of the purine-gout hypothesis was a prospective study from 2004 that found an association between dietary purines and gout. I think we need to consider other possibilities.

Is there anything else that elevates uric acid in humans? Ah, sugar, one of my favorite punching bags. You never let me down, old friend. Refined sugar (sucrose) increases serum uric acid under controlled conditions, as does fructose when compared to starch. This has never been demonstrated for purine-rich foods that I could find.

Another clue comes from a disorder called "hereditary fructose intolerance". These patients are missing an enzyme required for metabolizing fructose, and must avoid it or risk becoming very ill. Some of the relatives of these patients are "heterozygous" for the mutation, meaning they have one mutated copy of the gene and one normal copy. They can metabolize fructose, but at a slower rate than someone with two functional copies. And they also have a very high incidence of gout.

Tokelauan migrants to New Zealand consumed significantly more sugar than Tokelauans on Tokelau during this study period (13 vs. 8 percent of calories in 1982). This explanation makes much more sense to me than the idea that gout is caused by the very foods that have sustained us as long as our species has existed.

There is one piece that doesn't fit, however. If sugar is causing gout, then why didn't gout incidence increase on Tokelau as their sugar consumption increased? I don't know. Perhaps there is another factor involved as well. Any thoughts?

The Tokelau Island Migrant Study: Background and Overview
The Tokelau Island Migrant Study: Dental Health
The Tokelau Island Migrant Study: Cholesterol and Cardiovascular Health
The Tokelau Island Migrant Study: Weight Gain
The Tokelau Island Migrant Study: Diabetes
The Tokelau Island Migrant Study: Asthma