Does "Metabolically Healthy Obesity" Exist?

Obesity is strongly associated with metabolic alterations and negative health outcomes including diabetes, cardiovascular disease, and some types of cancer (1, 2, 3, 4).  Excess body fat is one of the primary causes of preventable health problems and mortality in the United States and many other affluent nations, ranking in importance with cigarette smoking and physical inactivity.  Obesity is thought to contribute to disease via the metabolic disturbances it causes, including excess glucose and lipids in the circulation, dysregulated hormone activity including insulin and leptin, and inflammatory effects.  This immediately raises two questions:

1. Does metabolically healthy obesity exist?
2. If so, are metabolically healthy obese people at an elevated risk of disease and death?

Does metabolically healthy obesity exist?

Read more »

The Mystery of the Northwestern Settlement - the Plot Thickens

A few weeks ago, we wrote about this curious case.

How the Case Stood

Northwester University, a prominent research university, settled charges it had mismanaged US government grant funds.  While it did not admit guilt, and specifically exonerated the faculty leader on whose watch the mismanagement allegedly occurred, the settlement and most of its coverage strongly suggested wrongdoing by the faculty member in charge of the scientific conduct of the grants, Professor Charles L Bennett.  While the alleged financial mismanagement was of funds in the mere millions, a relatively small amount as federal fraud cases go, and there were no allegations of anything harmful to patients, or of any research misconduct, the investigation involved multiple federal agencies, including the Federal Bureau of Investigation.  The settlement of charges of financial mismanagement, not research misconduct,  included unfavorable references to Dr Bennett, who as Principal Investigator should have been in charge of the scientific conduct of the grants, but not of their financial management.  Much bigger cases of alleged fraud, involving hundreds of millions of dollars, and potentially harm to patients due to overuse of dangerous drugs or devices, have not involved the FBI, and not included any disparagement of individuals who could have authorized, directed, or implemented the alleged misbehavior.

None of the initial press coverage noted the peculiarity of these aspects of the case, nor provided any explanations for them.      

Days later, the Cancer Letter published a long article in this case, which is now available without a subscription.  This article includes even more curiosities that raise even more questions.

Dr Bennett Found Irregularities, Sangoleye Pleaded Guilty, Nobody Noticed

In the original media coverage, Dr Bennett was accused based on complaints by a whistle blower.  For example, in an article in the Chicago Sun-Times,

 A whistleblower suit filed under seal in 2009 by former Lurie Cancer Center worker Melissa Theis first alleged the wrongdoing by Bennett.

However, the story in the Cancer Letter suggests Dr Bennett had tried to blow the whistle himself.  First,

Bennett said the allegations that he spent NCI money on dinners and vacations were inaccurate. He said he had encountered administrative irregularities at Northwestern and reported them to compliance officials.

In addition,

'I reported administrative issues by Northwestern University with my grants to the university compliance officer in 2006, just prior to my long-term bout with cancer that was diagnosed there,' Bennett said to The Cancer Letter. 'I have never had a single administrative discussion about the matter with anyone.'

Specifically,

Bennett’s statement about lax administration of grants at Northwestern appears to be bolstered by an aspect of the scandal that has escaped media attention even as multiple news stories in Chicago and national outlets focused on the settlement.

The Cancer Letter has learned that days before the settlement with Northwestern was announced, a former research administrator at the Division of Hematology and Oncology at the university’s medical school pled guilty to felony charges stemming from administration of Bennett’s NCI grants.

According to documents filed in the U.S. District Court for the Northern District of Illinois, Feyifunmi Sangoleye, the rogue administrator, set up an elaborate scheme to divert $86,000 to her personal accounts.The proceeds financed a wedding and a honeymoon in Europe, court documents say.

The article later included more detail,

Bennett said that he saw irregularities in the actions of the research administrator who handled his Research for Adverse Drug Events and Reports and that he has alerted the administration of the Division of Hematology and Oncology.

That same administrator, Sangoleye, pled guilty to larceny and theft, admitting to having embezzled NCI funds from Bennett’s program into a checking account created in the name of a fictitious contractor.

According to court documents, Sangoleye created a vendor code for a fictitious entity she called ATSDATA.

Then she created 10 false invoices from that entity and paid them with Northwestern’s checks.

The checks were sent to the ATSDATA post office box, which Sangoleye had rented, and placed into a bank account she created.

Between June 29, 2007, and July 29, 2008, ATSDATA received eight Northwestern checks that added up to $86,000. 'Sangoleye converted the proceeds of the ATSDATA checks to her own use and to the use of another' individual, the plea agreement states.

'I knew nothing about ATSDATA,' Bennett said in response to questions from The Cancer Letter. 'The administrator told me that ATSDATA was the billing address for the University of Illinois Survey Research Laboratory, a formal subcontractor. I did not know that the Survey Research Lab had any particular billing name. I have documented this to Jonathan Licht [chief of Northwestern’s Division of Hematology/Oncology] in 2008.'

So in summary, Dr Bennett, who was responsible for the scientific integrity but not the financial management of his grants, reported financial irregularities to Northwestern managers.  These reports lead to a guilty plea by a former Northwestern manager who admitted embezzling money.  However, this guilty plea was anechoic.  It did not appear in any media accounts.  The settlement negotiated between Northwestern University and the government did not acknowledge it.   


According to the Cancer Letter, Northwestern managers did not want to discuss the crimes of Sangoleye when the Cancer Letter brought it up,

 Northwestern officials declined to discuss Sangoleye, saying only that she had been employed by the university as a research administrator from February 2006 through August 2009.

The Cancer Letter suggested why the university might have had an interest in keeping the Sangoleye crimes and its settlement of the allegations about Dr Bennett apart.

Legal experts say that the final plea agreement between Sangoleye and the government would have weakened Northwestern’s position in negotiating the settlement. The final version of the plea agreement with Sangoleye was filed on July 25, just five days prior to the announcement of the government’s $3 million settlement with Northwestern.

Northwestern University might have had an interest in keeping the Sangoleye criminal case and its civil case separate.  However, the government did not obviously have such an interest.

Why did the government not address Sangoleye's crimes in the settlement it made with Northwestern University?

The Ambiguities of the Named Whistle Blower's Work

As we noted in our earlier post on this case, the role of the named whistle blower, Melissa Theis, was unclear, especially vis a vis Dr Bennett.  Although Dr Bennett as Principal Investigator of some of the grants involved ought not to have had any direct control of the financial management of the grants, Ms Theis apparently worked in some financial management capacity.  Yet Ms Theis apparently blew the whistle on the university, and on Dr Bennett for alleged financial, not research mismanagement.

The Cancer Letter raised new doubts about Ms Theis' role,

Several observers were surprised to see that the relator, Theis, was never employed by the cancer center.

According to her 2009 suit, Theis came to Northwestern as a temp two years earlier, in 2007, serving as a purchasing coordinator for the Division of Hematology and Oncology. The division, which is separate from the cancer center, administered all but one of the grants in question, the NIH database shows.

After a year, in 2008, Theis was hired as a fulltime employee of the Northwestern Medical Faculty Foundation. The foundation, which runs the medical practice, is also separate from the cancer center. She left Northwestern in October 2008.

'Theis specifically noted that invoices were submitted for consultants and services that were never included in the initial grant budget,' the complaint states. 'Invoices were submitted for consultants and services that were significantly in excess of the amount budgeted for the grant, and many of the consultants and vendors failed to provide detailed information about the actual services rendered.'

Again, in the usual practice, such invoices might have been requested by a grant investigator, but the requests would have to have been vetted and then the invoices would have to have been generated by managers, not scientists or physicians. 

Who really administered these grants, and why did the settlement minimize the responsibility of university managers while apparently blaming scientists for bad financial management?

Dr Bennett's Supporters and Enemies

In our first post on this case, we had contrasted how the settlement and media coverage of it appeared to heap blame upon Dr Bennett alone, while not attaching any responsibility to his academic supervisor on one hand, or any university managers on the other.  We noted that Dr Bennett, after having been a consultant for Amgen,  had become known as a "pharmascold," a skeptic of pharmaceutical industry practices, and the author of research that suggested one Amgen product was more hazardous than had been previously thought.  His supervisor, on the other hand, had multiple ongoing financial ties to the pharmaceutical industry.

The Cancer Letter suggested others were trying to connect related dots. First, in general,

Making enemies is an exhaustively studied side effect of probing the safety of cancer drugs, and during much of the period in question, Bennett was producing more than his standard quota of foes.

In particular,

Now, researchers who worked with Bennett on the ESA issues are puzzled by his legal problems.

'Charlie has been an important voice in raising concerns regarding the use of erythropoietin in patients with cancer,' said Anthony Blau, co-director, Institute for Stem Cell and Regenerative Medicine at the University of Washington. 'In particular, his 2008 metaanalysis, published in JAMA, heightened awareness of the issue and helped to reduce the indiscriminate use of erythropoietin in cancer patients.'

Blau is a co-author on the JAMA paper [as noted in our previous post.]

'This doesn’t really fit in his picture,' said Michael Henke, a radiation oncologist in Freiburg, Germany, who was the first to stumble across potential problems stemming from overuse of ESAs.

'You might recall, we got in contact in 2003 when our group communicated potential dismal effects of erythropoietin on cancer patients—a story not really appreciated these days because of economic interests,'  Henke said referring to the pioneering paper in The Lancet. Henke was the senior author on the JAMA paper.

'However, Dr. Bennett and we consistently gathered additional data that were finally reported as a meta-analysis in 2008. Consequently, erythropoietin prescriptions dramatically decreased, eventually prolonging or even saving lives of cancer patients.'

'While collaborating, I did learn him as extraordinarily active, alert-eyed colleague who strictly adhered to serious scientific conduct and to the wellbeing of patients.'

Henke confesses to wondering whether the many powerful enemies Bennett made in the pharmaceutical and biotechnology industries have struck back.

'We shouldn’t feed paranoia,' Henke said.  'However, given the exclusively positive experience when collaborating with his group, makes me wonder whether this litigation might follow some very particular other issues.'

Did Dr Bennett's transformation from a consultant to to a fierce scientific skeptic of the pharmaceutical industry influence the handling of this case, and its media coverage?

Summary

The coverage by the Cancer Letter underscores our previous concerns, so I will simply repeat the summary from my last post.

The settlement by Northwestern University, which was mainly about allegations made against Dr Charles L Bennett, who was not a party to the settlement, was very different that the vast majority of the march of legal settlements whose continuation we have frequently discussed.

The settlement and its media coverage raised important questions whose answers would be important to the assessment of  our current regulatory and legal response to misbehavior by and within large health care organizations.  Health Care Renewal is about raising such issues by commenting on public information, media reports, and research.  I hope those with capacity to investigate will consider these questions.  Inquiring minds want to know.

ADDENDUM (27 August, 2013) - See also comments by Dr Howard Brody on the Hooked: Ethics, Medicine and Pharma blog.


Roy M. Poses MD in Health Care Renewal 

The Dangers of Big Corporate Health Care: Deceptive Marketing of Cancer Treatments

A series of articles over the last few months, culminating in an investigative report by Reuters, provided the newest example of what can go wrong when corporations provide direct care to vulnerable patients.  In this case, the vulnerable patients had cancer, and the corporation that provided them care was the Cancer Treatment Centers of America (CTCA).  I will try to go through the case chronologically.

As Rueters reported, CTCA "was founded in 1988 by Richard J. Stephenson, who has been chairman ever since."

The Founder's Checkered Past

A Misdemeanor

As Reuters noted,

A graduate of Northwestern University Law School, Stephenson started out as an investment banker. In 1966 he became a trustee of Americans Building Constitutionally, an organization that helped wealthy individuals set up not-for-profit corporations and personal trusts to avoid paying federal income and inheritance taxes.

In 1969, a California state court found the group's top official and six others guilty of grand theft or conspiring to commit grand theft. Stephenson had pleaded no contest to false advertising, a misdemeanor, and testified for the state, according to media reports at the time.

Allegations of Use of Unproven Cancer Treatments

Stephenson seemingly stayed out of trouble until 1975, but

Stephenson ventured into healthcare in 1975, when he and partners bought Zion-Benton Hospital in Zion, Illinois, renaming it American International Hospital. By the late 1980s, American International was facing financial problems and its 'reputation had been severely damaged' by local press reports about its use of unproven cancer treatments, according to a 2004 court opinion on a successful petition by a former CTCA president seeking an increased valuation for his share of the company.

CTCA: No More Unsubstantiated Claims

Apparently around the time American International Hospital starting having major troubles, Stephenson branched out,

In 1988, Stephenson founded CTCA. He was motivated, said CEO Bonner, by the difficulty he had identifying and obtaining the best therapies for his mother after she developed bladder cancer. She died in 1982.

By 1996, CTCA got into trouble too,

 

Cancer Treatment Centers of America got in trouble with regulators in 1996, when the Federal Trade Commission accused it of, among other things, presenting survival claims it couldn't support. The company entered into a consent decree with the FTC and, without admitting any of the allegations, agreed not to make unsubstantiated outcomes claims.

"Unscientific Therapies"

As far as I can tell, all was then quiet until 2012.  Late that year, a Forbes columnist wrote,

 Alongside standard, science-based cancer therapies, CTCA also offers an array of questionable, unscientific therapies, which it proudly labels as part of its 'integrative cancer treatment.'  CTCA advertises many such treatments, including:

* Acupuncture
* Acupressure
* Chiropractic
* Naturopathy
* Homeopathy
* Mind-Body medicine (including Reiki and Qi Gong)

None of the treatments in this list has any scientific support showing that they provide a benefit to cancer patients.  Some of them carry a real risk of harm, as I’ve written about previously.

He further charged,

CTCA makes multiple unsupported, unscientific claims for its alternative treatments, such as:

• 'Naturopathic medicine can help reduce these [cancer-related] symptoms, strengthen the immune system and support the healing process throughout your brain cancer treatment.'
• 'Acupuncture may help to alleviate [cancer] treatment-related side effects, such as nausea and vomiting.'
• 'When used during your leukemia treatment, our chiropractic care services can help correct bone, muscle and joint problems and restore nerve function.'

These are just a few examples. These claims, and CTCA’s marketing of the therapies involved, present a huge ethical problem.

Manipulated Survival Statistics

Then, in March 2012, the Reuters investigative reporters charged that CTCA manipulated its survival statistics to make its results look better.

CTCA reports on its website that the percentage of its patients who are alive after six months, a year, 18 months and longer regularly tops national figures. For instance, 60 percent of its non-small-cell lung cancer patients are alive at six months, CTCA says, compared to 38 percent nationally. And 64 percent of its prostate cancer patients are alive at three years, versus 38 percent nationally.

Such claims are misleading, according to nine experts in cancer and medical statistics whom Reuters asked to review CTCA's survival numbers and its statistical methodology.

The experts were unanimous that CTCA's patients are different from the patients the company compares them to, in a way that skews their survival data. It has relatively few elderly patients, even though cancer is a disease of the aged. It has almost none who are uninsured or covered by Medicaid - patients who tend to die sooner if they develop cancer and who are comparatively numerous in national statistics.

Carolyn Holmes, a former CTCA oncology information specialist in Tulsa, Oklahoma, said she and others routinely tried to turn away people who 'were the wrong demographic' because they were less likely to have an insurance policy that CTCA preferred. Holmes said she would try to 'let those people down easy.'

Equally significant, CTCA includes in its outcomes data only those patients 'who received treatment at CTCA for the duration of their illness' - patients who have the ability to travel to CTCA locations from the get-go, without seeking local treatment first. That means excluding, for example, those who have exhausted treatment options closer to home and arrive at a CTCA facility with advanced disease.

Accepting only selected patients and calculating survival outcomes from only some of them 'is a huge bias and gives an enormous advantage to CTCA,' said biostatistician Donald Berry of MD Anderson Cancer Center in Houston.

Furthermore,

CTCA also appears to exclude the vast majority of its patients when it calculates survival data. In survival results from 2004 to 2008 posted on its website, CTCA reported 61 patients with advanced prostate cancer, 97 with advanced breast cancer, 434 with advanced lung cancer, and 165 with advanced colon or rectal cancer. These are the four most common solid tumors. In the same period, CTCA treated thousands of patients at its Zion facility alone, according to filings with state regulators.

'We agree that some of our sample sizes' are small 'and have always stated this as a limitation of our study,' said Xiong, the consultant to CTCA.

'I'd have some concerns about why and wonder if some cherry-picking was going on,' said Spectrum Health's Campbell.

Moreover, while the standard reporting period for cancer survival is five years after diagnosis, CTCA on its website doesn't go that far; for the four most common tumors, it reports survival up to four years at most. And as Reuters found, the company's advantage often diminishes as the five-year mark approaches

 
The Founder's Checkered Present

By the way, also in the last few months, watchdog groups have asked for an investigation of CTCA's founder for possible deceptive actions that might have violated US election laws.  In December, 2012, the Washington Post reported

In the weeks before the election, more than $12 million in donations was funneled through two Tennessee corporations to the FreedomWorks super PAC after negotiations with [CTCA Founder Richard J] Stephenson over a preelection gift of the same size, according to three current and former employees with knowledge of the arrangement.

Then,

 Two watchdog groups last week asked the Federal Election Commission and the Justice Department to investigate the donations from the two Tennessee companies. The groups, Democracy 21 and the Campaign Legal Center, say the arrangement could violate federal laws that prohibit attempting to hide the true source of a political contribution by giving it under another name.

Summary

In summary, there are now charges in the media that Cancer Treatment Centers of America manipulated its survival data to makes its advertised results appear better, while it also advertises unproven complementary and alternative medicine treatments  as effective.  In the past the company had signed a consent decree not to make (presumably any more) unsubstantiated claims.  Meanwhile, the company's founder, who has a past history of a no contest plea to false advertising, and who had previously run a hospital system also charged with making unsupported survival claims, has been accused of hiding political donations.

Thus this organization, run by someone who has his own history of deception, has been found to make exaggerated and/or unsubstantiated advertising claims of several types and at different times.  These claims could attract vulnerable patients who perhaps could get better care elsewhere, possibly leading to excess morbidity and even early mortality. 

So Cancer Treatment Centers of America seems to be the latest reason to worry about the laissez faire US system which allows lightly regulated for-profit corporations to provide direct "care" to our most vulnerable patients.   We have recently discussed how a for-profit hospital chain may have been over treating some patients and under treating others, possibly risking patients' health to increase revenues (look here);  how for-profit hospice corporations by enrolling patients who do not actually have terminal illness for palliative care only  could be denying potentially curative treatment to curable patients (look here); and how for-profit mental health clinics and drug treatment centers could be providing shoddy, and potentially dangerous care to boost revenues (look here and here).

We will see if the newest part of the pattern of news reports about CTCA and its founder, coupled with reports about other for-profit health care corporations that provide direct care to vulnerable patients provoke any official action.  However, the pattern is substantial enough so that it should make all health care professionals and all patients  reconsider whether ever to trust a for-profit hospital system, hospital, clinic or other site providing direct health care to patients.

On a policy level, as I have said before,....   In my humble opinion, before the health care bubble bursts, we need to challenge the notion that direct health care should ever be provided, or that medicine ought to be practiced by for-profit corporations. Before market fundamentalism became so prominent, many states prohibited the corporate practice of medicine, and the American Medical Association forbade the commercialization of medicine.

 It is time to heed that wisdom. I submit that we will not be able to have good quality, accessible health care at an affordable price until we restore physicians as independent, ethical health care professionals, and until we restore small, independent, community responsible, non-profit hospitals as the locus for inpatient care.

Does Calorie Restriction Extend Lifespan in Mammals?

Until about two years ago, the story went something like this: calorie restriction extends lifespan in yeast, worms, flies, and rodents.  Lifespan extension by calorie restriction appears to be biologically universal, therefore it's probably only a matter of time until it's demonstrated in humans as well.  More than 20 years ago, independent teams of researchers set out to demonstrate the phenomenon in macaque monkeys, a primate model closer to humans than any lifespan model previously tested.

Recent findings have caused me to seriously question this narrative.  One of the first challenges was the finding that genetically wild mice (as opposed to inbred laboratory strains) do not live longer when their calorie intake is restricted, despite showing hormonal changes associated with longevity in other strains, although the restricted animals do develop less cancer (1).  One of the biggest blows came in 2009, when researchers published the results of a study that analyzed the effect of calorie restriction on lifespan in 41 different strains of mice, both male and female (2).  They found that calorie restriction extends lifespan in a subset of strains, but actually shortens lifespan in an even larger subset.  Below is a graph of the effect of calorie restriction on lifespan in the 41 strains.  Positive numbers indicate that calorie restriction extended life, while negative numbers indicate that it shortened life:

Read more »

Rendering Unto Caesar - What the Abramson Family Cancer Research Institute vs Thompson Says About the Loss of the Academic Medical Mission

A case, reported by the New York Times as involving an intellectual property dispute, should create a lot of cognitive dissonance about the state of the academic medical mission.

Litigation Involving the Abramson Family Cancer Research Institute and Dr Craig B Thompson

Here is how the Times outlined the story:

The president of Memorial Sloan-Kettering Cancer Center in New York is in a billion-dollar dispute with his former workplace, a cancer institute at the University of Pennsylvania, over accusations that he walked away with groundbreaking research and used it to help start a valuable biotechnology company.

In a lawsuit, the Leonard and Madlyn Abramson Family Cancer Research Institute at Penn described its former scientific director, Dr. Craig B. Thompson, as 'an unscrupulous doctor' who 'chose to abscond with the fruits of the Abramson largess.'

In particular,

In the suit, the Abramson cancer institute, which has received more than $100 million from the philanthropist Leonard Abramson and his family, says that Dr. Thompson concealed his role in starting Agios, which has attracted investors with a potentially new way to treat cancer. The institute says Dr. Thompson’s actions deprived it of proceeds that could support future research, causing it damages that could exceed $1 billion.

So presumably the Abramson Institute is alleging that Thompson took its intellectual property and put it into Agios, and the Institute therefore wants compensation. Note that the Institute does not appear to be alleging either that Thompson was supposed to be its employee, but actually was working for Agios at the time he was supposed to be working for the institute; or that Thompson hid a a conflict of interest created by his financial relationship with Agios that could have affected how he fulfilled his professional responsibilities there.

Note further that certain other parties declared that they are not part of this dispute. These included Dr Thompson's current employer:

Sloan-Kettering declined to comment, saying it was not a party to the lawsuit....

These also included the University of Pennsylvania:

Susan E. Phillips, senior vice president for Penn Medicine, said that the suit had been filed not by the university but by the research institute, a separate entity. She said the university was investigating the accusations.

The nature of this dispute ought to generate several kinds of cognitive dissonance.

Protecting Intellectual Property vs Upholding the Academic Mission at the University of Pennsylvania

On one of its web pages, the Abramson Family Cancer Research Institute describes its history:

The Abramson Cancer center of the University of Pennsylvania provides each patient with exemplary care though a comprehensive team approach, personalized service, education and outreach, and nationally recognized cancer research programs.

The web page describes the institute as simply part of the larger University of Pennsylvania cancer center, which came to be named for the Abramson family:

Penn's Cancer Center was renamed in 2002 as the Abramson Cancer Center of the University of Pennsylvania, recognizing the Abramson family's $100 million commitment to support comprehensive cancer research and care.

Thus it seems that the Abramson institute is simply a piece of a traditional academic medical center.

The academic mission is traditionally described as the creation and teaching of knowledge. Thus, if an academic institution creates new knowledge, its should then disseminate it, not own it. Of course, in the US, since the Bayh-Dole act was passed, academic institutions were given the ability to patent their discoveries, and began to protect and sequester the knowledge they contained, rather than disseminating it.

In this case, however, one part of a large university and a large academic medical center seems to be concentrating entirely on its right of ownership of intellectual property, not the traditional academic mission. The fact that this dispute has lead to litigation suggests that the academic organization is now intent on protecting, rather than disseminating knowledge. The dispute appears to be between a commercial research company and its allegedly errant former hired manager.

The Abramson Institute: Part or Independent of the Academic Medical Center?  

A little more digging suggests that the nature of the Abramson institute is not as clear as is described in its web-page. A GuideStar search revealed that the institute is actually legally independent from the university. It filed its own 990 form (latest version, covering 2009-2010, here.)

The filing did list various entities, including the Clinical Care Associates of the University of Pennsylvania Health System, and the Trustees of the University of Pennsylvania as "related tax-exempt organizations."

However, this filing should create cognitive dissonance about what the underlying nature of the Institute? Is it part of the University of Pennsylvania and its medical center, or is independent but cooperating?

This dissonance is only enhanced by the ambiguous response of the University of Pennsylvania to the lawsuit. If the Institute is part of the University, then the University ought to be party to the lawsuit, it would seem.

This filing with the US government did underline the Institute's commitment to disseminating research. A description of its tax "exempt purposes" included:

Education - scientists at the Institute actively share their discoveries with the research community, physicians, and students.

As above, this statement of purpose appears not to fit with the filing of a lawsuit to obtain damages due to the alleged taking of intellectual property. If this really were the Institute's mission, would not they want the intellectual property liberated so it could be actively shared? The cognitive dissonance about the mission of the Institute and of the University versus the protection and sequestration of intellectual property is thus increased.

Upholding the Academic Mission vs Staying Uninvolved at Memorial Sloan-Kettering Cancer Center

As an aside, note that Dr Thompson is now not just working for Agios. In fact, he has been President of the Memorial Sloan-Kettering Cancer Center since 2010 (look here). Just like the Abramson Cancer Center, Sloan-Kettering is an academic medical center with the traditional mission of teaching, research, and patient care. Here is its mission statement:

As one of the world's premier cancer centers, Memorial Sloan-Kettering Cancer Center is committed to exceptional patient care, leading-edge research, and superb educational programs.

So one would think that people there ought to be concerned by allegations that its current president took intellectual property without authorization, and that he is "an unscrupulous doctor." If these allegations were to be proven false, they seemingly would represent a major, unwarranted slur on its and his reputation. If they were to be proven true, they would indicate that current leadership might not have the character to uphold the mission. Either outcome would be serious and have serious implications. However, at the moment, this noted academic medical institution has expressed neither outrage about possibly false accusations nor resolve to investigate the matter and then weed out any leaders not devoted to the mission.

Thus, the apparent intention of the leadership of Memorial Sloan-Kettering to stay uninvolved with this case ought to generate more cognitive dissonance.


Summary

The cognitive dissonances evoked by the case of the Abramson Institute vs Dr Thompson ought to inspire questions about what our academic medical institutions have become.  While they proclaim their devotion to research and teaching to improve health and health care, and advance science, they may increasingly act like commercial research organizations whose main goal is to generate increased revenue from products and services, and in this case, from intellectual property. 

It is hard to see how this emphasis on holding onto rather than disseminating new knowledge will be good in the long run for science, learning, or patient care.

We are now a good 30+ years into our ill-fated American experiment about the effects of turning medicine commercial and making health care a commodity. So far, it has yielded the highest costs in the world, but declining access, mediocre quality, and demoralized professionals.  Squabbling among top researchers and leading academic medical institutions over the ownership of intellectual property for the sake of revenue, not dissemination, is the latest symbol of the decline of our health care.

I can only hope that all the parties involved suddenly remember that they are supposed to be creating and disseminating knowledge, not just getting rich. 

Oltipraz

Oltipraz is a drug that was originally used to treat intestinal worms. It was later found to prevent a broad variety of cancers (1). This was attributed to its ability to upregulate cellular detoxification and repair mechanisms.

Researchers eventually discovered that oltipraz acts by activating Nrf2, the same transcription factor activated by ionizing radiation and polyphenols (2, 3, 4). Nrf2 activation mounts a broad cellular protective response that appears to reduce the risk of multiple health problems.

A recent paper in Diabetologia illustrates this (5). Investigators put mice on a long-term refined high-fat diet, with or without oltipraz. These carefully crafted diets are very unhealthy indeed, and when fed to rodents they rapidly induce fat gain and something that looks similar to human metabolic syndrome (insulin resistance, abdominal adiposity, blood lipid disturbances). Adding oltipraz to the diet prevented the fat gain, insulin resistance and inflammatory changes that occurred in the refined high-fat diet group.

The difference in fasting insulin was remarkable. The mice taking oltipraz had 1/7 the fasting insulin of the refined high-fat diet comparison group, and 1/3 the fasting insulin of the low-fat comparison group! Yet their glucose tolerance was normal, indicating that they were not low on insulin due to pancreatic damage. The low-fat diet they used in this study was also refined, which is why the two control groups (high-fat and low-fat) didn't diverge more in body fatness and other parameters. If they had used a group fed unrefined rodent chow as the comparator, the differences between groups would have been larger.

This shows that in addition to preventing cancer, Nrf2 activation can attenuate the metabolic damage caused by an unhealthy diet in rodents. Oltipraz illustrates the power of the cellular hormesis response. We can exploit this pathway naturally using polyphenols and other chemicals found in whole plant foods.

Polyphenols, Hormesis and Disease: Part II

In the last post, I explained that the body treats polyphenols as potentially harmful foreign chemicals, or "xenobiotics". How can we reconcile this with the growing evidence that at least a subset of polyphenols have health benefits?

Clues from Ionizing Radiation

One of the more curious things that has been reported in the scientific literature is that although high-dose ionizing radiation (such as X-rays) is clearly harmful, leading to cancer, premature aging and other problems, under some conditions low-dose ionizing radiation can actually decrease cancer risk and increase resistance to other stressors (1, 2, 3, 4, 5). It does so by triggering a protective cellular response, increasing cellular defenses out of proportion to the minor threat posed by the radiation itself. The ability of mild stressors to increase stress resistance is called "hormesis." Exercise is a common example. I've written about this phenomenon in the past (6).

The Case of Resveratrol

Resveratrol is perhaps the most widely known polyphenol, available in supplement stores nationwide. It's seen a lot of hype, being hailed as a "calorie restriction mimetic" and the reason for the "French paradox."* But there is quite a large body of evidence suggesting that resveratrol functions in the same manner as low-dose ionizing radiation and other bioactive polyphenols: by acting as a mild toxin that triggers a hormetic response (7). Just as in the case of radiation, high doses of resveratrol are harmful rather than helpful. This has obvious implications for the supplementation of resveratrol and other polyphenols. A recent review article on polyphenols stated that while dietary polyphenols may be protective, "high-dose fortified foods or dietary supplements are of unproven efficacy and possibly harmful" (8).

The Cellular Response to Oxidants

Although it may not be obvious, radiation and polyphenols activate a cellular response that is similar in many ways. Both activate the transcription factor Nrf2, which activates genes that are involved in detoxification of chemicals and antioxidant defense**(9, 10, 11, 12). This is thought to be due to the fact that polyphenols, just like radiation, may temporarily increase the level of oxidative stress inside cells. Here's a quote from the polyphenol review article quoted above (13):

We have found that [polyphenols] are potentially far more than 'just antioxidants', but that they are probably insignificant players as 'conventional' antioxidants. They appear, under most circumstances, to be just the opposite, i.e. prooxidants, that nevertheless appear to contribute strongly to protection from oxidative stress by inducing cellular endogenous enzymic protective mechanisms. They appear to be able to regulate not only antioxidant gene transcription but also numerous aspects of intracellular signaling cascades involved in the regulation of cell growth, inflammation and many other processes.

It's worth noting that this is essentially the opposite of what you'll hear on the evening news, that polyphenols are direct antioxidants. The scientific cutting edge has largely discarded that hypothesis, but the mainstream has not yet caught on.

Nrf2 is one of the main pathways by which polyphenols increase stress resistance and antioxidant defenses, including the key cellular antioxidant glutathione (14). Nrf2 activity is correlated with longevity across species (15). Inducing Nrf2 activity via polyphenols or by other means substantially reduces the risk of common lifestyle disorders in animal models, including cardiovascular disease, diabetes and cancer (16, 17, 18), although Nrf2 isn't necessarily the only mechanism. The human evidence is broadly consistent with the studies in animals, although not as well developed.

One of the most interesting effects of hormesis is that exposure to one stressor can increase resistance to other stressors. For example, long-term consumption of high-polyphenol chocolate increases sunburn resistance in humans, implying that it induces a hormetic response in skin (19). Polyphenol-rich foods such as green tea reduce sunburn and skin cancer development in animals (20, 21).

Chris Masterjohn first introduced me to Nrf2 and the idea that polyphenols act through hormesis. Chris studies the effects of green tea on health, which seem to be mediated by polyphenols.

A Second Mechanism

There is a place in the body where polyphenols are concentrated enough to be direct antioxidants: in the digestive tract after consuming polyphenol-rich foods. Digestion is a chemically harsh process that readily oxidizes ingested substances such as polyunsaturated fats (22). Oxidized fat is neither healthy when it's formed in the deep fryer, nor when it's formed in the digestive tract (23, 24). Eating polyphenol-rich foods effectively prevents these fats from being oxidized during digestion (25). One consequence of this appears to be better absorption and assimilation of the exceptionally fragile omega-3 polyunsaturated fatty acids (26).

What does it all Mean?

I think that overall, the evidence suggests that polyphenol-rich foods are healthy in moderation, and eating them on a regular basis is generally a good idea. Certain other plant chemicals, such as suforaphane found in cruciferous vegetables, and allicin found in garlic, exhibit similar effects and may also act by hormesis (27). Some of the best-studied polyphenol-rich foods are tea (particularly green tea), blueberries, extra-virgin olive oil, red wine, citrus fruits, hibiscus tea, soy, dark chocolate, coffee, turmeric and other herbs and spices, and a number of traditional medicinal herbs. A good rule of thumb is to "eat the rainbow", choosing foods with a variety of colors.

Supplementing with polyphenols and other plant chemicals in amounts that would not be achievable by eating food is probably not a good idea.


* The "paradox" whereby the French eat a diet rich in saturated fat, yet have a low heart attack risk compared to other affluent Western nations.

** Genes containing an antioxidant response element (ARE) in the promoter region. ARE is also sometimes called the electrophile response element (EpRE).

Tropical Plant Fats: Coconut Oil, Part II

Heart Disease: Animal Studies

Although humans aren't rats, animal studies are useful because they can be tightly controlled and experiments can last for a significant portion of an animal's lifespan. It's essentially impossible to do a tightly controlled 20-year feeding study in humans.

The first paper I'd like to discuss come from the lab of Dr. Thankappan Rajamohan at the university of Kerala (1). Investigators fed three groups of rats different diets:

1. Sunflower oil plus added cholesterol
2. Copra oil, a coconut oil pressed from dried coconuts, plus added cholesterol
3. Freshly pressed virgin coconut oil, plus added cholesterol

Diets 1 and 2 resulted in similar lipids, while diet 3 resulted in lower LDL and higher HDL. A second study also showed that diet 3 resulted in lower oxidized LDL, a dominant heart disease risk factor (2). Overall, these papers showed that freshly pressed virgin coconut oil, with its full complement of "minor constituents"*, partially protects rats against the harmful effects of cholesterol overfeeding. These are the only papers I could find on the cardiovascular effects of unrefined coconut oil in animals!

Although unrefined coconut oil appears to be superior, even refined coconut oil isn't as bad as it's made out to be. For example, compared to refined olive oil, refined coconut oil protects against atherosclerosis (hardening and thickening of the arteries) in a mouse model of coronary heart disease (LDL receptor knockout). In the same paper, coconut oil caused more atherosclerosis in a different mouse model (ApoE knockout) (3). So the vascular effects of coconut oil depend in part on the animals' genetic background.

In general, I've found that the data are extremely variable from one study to the next, with no consistent trend showing refined coconut oil to be protective or harmful relative to refined monounsaturated fats (like olive oil) (4). In some cases, polyunsaturated oils cause less atherosclerosis than coconut oil in the context of an extreme high-cholesterol diet because they sometimes lead to blood lipid levels that are up to 50% lower. However, even this isn't consistent across experiments. Keep in mind that atherosclerosis is only one factor in heart attack risk.

What happens if you feed coconut oil to animals without adding cholesterol, and without giving them genetic mutations that promote atherosclerosis? Again, the data are contradictory. In rabbits, one investigator showed that serum cholesterol increases transiently, returning to baseline after about 6 months, and atherosclerosis does not ensue (5). A different investigator showed that coconut oil feeding results in lower blood lipid oxidation than sunflower oil (6). Yet a study from the 1980s showed that in the context of a terrible diet composition (40% sugar, isolated casein, fat, vitamins and minerals), refined coconut oil causes elevated blood lipids and atherosclerosis (7). This is almost certainly because overall diet quality influences the response to dietary fats in rabbits, as it does in other mammals.

Heart Disease: Human Studies

It's one of the great tragedies of modern biomedical research that most studies focus on nutrients rather than foods. This phenomenon is called "nutritionism". Consequently, most of the studies on coconut oil used a refined version, because the investigators were most interested in the effect of specific fatty acids. The vitamins, polyphenols and other minor constituents of unrefined oils are eliminated because they are known to alter the biological effects of the fats themselves. Unfortunately, any findings that result from these experiments apply only to refined fats. This is the fallacy of the "X fatty acid does this and that" type statements-- they ignore the biological complexity of whole foods. They would probably be correct if you were drinking purified fatty acids from a beaker.

Generally, the short-term feeding studies using refined coconut oil show that it increases both LDL ("bad cholesterol") and HDL ("good cholesterol"), although there is so much variability between studies that it makes firm conclusions difficult to draw (8, 9). As I've written in the past, the ability of saturated fats to elevate LDL appears to be temporary; both human and certain animal studies show that it disappears on timescales of one year or longer (10, 11). That hasn't been shown specifically for coconut oil that I'm aware of, but it could be one of the reasons why traditional cultures eating high-coconut diets don't have elevated serum cholesterol.

Another marker of cardiovascular disease risk is lipoprotein (a), abbreviated Lp(a). This lipoprotein is a carrier for oxidized lipids in the blood, and it correlates with a higher risk of heart attack. Refined coconut oil appears to lower Lp(a), while refined sunflower oil increases it (12).

Unfortunately, I haven't been able to find any particularly informative studies on unrefined coconut oil in humans. The closest I found was a study from Brazil showing that coconut oil reduced abdominal obesity better than soybean oil in conjunction with a low-calorie diet, without increasing LDL (13). It would be nice to have more evidence in humans confirming what has been shown in rats that there's a big difference between unrefined and refined coconut oil.

Coconut Oil and Body Fat

In addition to the study mentioned above, a number of experiments in animals have shown that "medium-chain triglycerides", the predominant type of fat in coconut oil, lead to a lower body fat percentage than most other fats (14). These findings have been replicated numerous times in humans, although the results have not always been consistent (15). It's interesting to me that these very same medium-chain saturated fats that are being researched as a fat loss tool are also considered by mainstream diet-heart researchers to be among the most deadly fatty acids.

Coconut Oil and Cancer

Refined coconut oil produces less cancer than seed oils in experimental animals, probably because it's much lower in omega-6 polyunsaturated fat (16, 17). I haven't seen any data in humans.

The Bottom Line

There's very little known about the effect of unrefined coconut oil on animal and human health, however what is published appears to be positive, and is broadly consistent with the health of traditional cultures eating unrefined coconut foods. The data on refined coconut oil are conflicting and frustrating to sort through. The effects of refined coconut oil seem to depend highly on dietary context and genetic background. In my opinion, virgin coconut oil can be part of a healthy diet, and may even have health benefits in some contexts.


* Substances other than the fat itself, e.g. vitamin E and polyphenols. These are removed during oil refining.

Tropical Plant Fats: Palm Oil

A Fatal Case of Nutritionism

The concept of 'nutritionism' was developed by Dr. Gyorgy Scrinis and popularized by the food writer Michael Pollan. It states that the health value of a food can be guessed by the sum of the nutrients it contains. Pollan argues, I think rightfully, that nutritionism is a reductionist philosophy that assumes we know more about food composition and the human body than we actually do. You can find varying degrees of this philosophy in most mainstream discussions of diet and health*.

One conspicuous way nutritionism manifests is in the idea that saturated fat is harmful. Any fat rich in saturated fatty acids is typically assumed to be unhealthy, regardless of its other constituents. There is also apparently no need to directly test that assumption, or even to look through the literature to see if the assumption has already been tested. In this manner, 'saturated' tropical plant fats such as palm oil and coconut oil have been labeled unhealthy, despite essentially no direct evidence that they're harmful. As we'll see, there is actually quite a bit of evidence, both indirect and direct, that their unrefined forms are not harmful and perhaps even beneficial.

Palm Oil and Heart Disease

Long-time readers may recall a post I wrote a while back titled Ischemic Heart Attacks: Disease of Civilization (1). I described a study from 1964 in which investigators looked for signs of heart attacks in thousands of consecutive autopsies in the US and Africa, among other places. They found virtually none in hearts from Nigeria and Uganda (3 non-fatal among more than 4,500 hearts), while Americans of the same age had very high rates (up to 1/3 of hearts).

What do they eat in Nigeria? Typical Nigerian food involves home-processed grains, starchy root vegetables, beans, fruit, vegetables, peanuts, red palm oil, and a bit of dairy, fish and meat**. The oil palm Elaeis guineensis originated in West Africa and remains one of the main dietary fats throughout the region.

To extract the oil, palm fruit are steamed, and the oily flesh is removed and pressed. It's similar to olive oil in that it is extracted gently from an oil-rich fruit, rather than harshly from an oil-poor seed (e.g., corn or soy oil). The oil that results is deep red and is perhaps the most nutrient-rich fat on the planet. The red color comes from carotenes, but red palm oil also contains a large amount of vitamin E (mostly tocotrienols), vitamin K1, coenzyme Q10 and assorted other fat-soluble constituents. This adds up to a very high concentration of fat-soluble antioxidants, which are needed to protect the fat from rancidity in hot and sunny West Africa. Some of these make it into the body when it's ingested, where they appear to protect the body's own fats from oxidation.

Mainstream nutrition authorities state that palm oil should be avoided due to the fact that it's approximately half saturated. This is actually one of the main reasons palm oil was replaced by hydrogenated seed oils in the processed food industry. Saturated fat raises blood cholesterol, which increases the risk of heart disease. Doesn't it? Let's see what the studies have to say.

Most of the studies were done using refined palm oil, unfortunately. Besides only being relevant to processed foods, this method also introduces a new variable because palm oil can be refined and oxidized to varying degrees. However, a few studies were done with red palm oil, and one even compared it to refined palm oil. Dr. Suzanna Scholtz and colleagues put 59 volunteers on diets predominating in sunflower oil, refined palm oil or red palm oil for 4 weeks. LDL cholesterol was not different between the sunflower oil and red palm oil groups, however the red palm oil group saw a significant increase in HDL. LDL and HDL both increased in the refined palm oil group relative to the sunflower oil group (2).

Although the evidence is conflicting, most studies have not been able to replicate the finding that refined palm oil increases LDL relative to less saturated oils (3, 4). This is consistent with studies in a variety of species showing that saturated fat generally doesn't raise LDL compared to monounsaturated fat in the long term, unless a large amount of purified cholesterol is added to the diet (5).

Investigators have also explored the ability of palm oil to promote atherosclerosis, or hardening and thickening of the arteries, in animals. Not only does palm oil not promote atherosclerosis relative to monounsaturated fats (e.g., olive oil), but in its unrefined state it actually protects against atherosclerosis (6, 7). A study in humans hinted at a possible explanation: compared to a monounsaturated oil***, palm oil greatly reduced oxidized LDL (8). As a matter of fact, I've never seen a dietary intervention reduce oxLDL to that degree (69%). oxLDL is a major risk factor for cardiovascular disease, and a much better predictor of risk than the typically measured LDL cholesterol (9). The paper didn't state whether or not the palm oil was refined. I suspect it was lightly refined, but still rich in vitamin E and CoQ10.

As I discussed in my recent interview with Jimmy Moore, atherosclerosis is only one factor in heart attack risk (10). Several other factors are also major determinants of risk: clotting tendency, plaque stability, and susceptibility to arrhythmia. Another factor that I haven't discussed is how resistant the heart muscle is to hypoxia, or loss of oxygen. If the coronary arteries are temporarily blocked-- a frequent occurrence in modern people-- the heart muscle can be damaged. Dietary factors determine the degree of damage that results. For example, in rodents, nitrites derived from green vegetables protect the heart from hypoxia damage (11). It turns out that red palm oil is also protective (12, 13). Red palm oil also protects against high blood pressure in rats, an effect attributed to its ability to reduce oxidative stress (14, 15).

Together, the evidence suggests that red palm oil does not contribute to heart disease risk, and in fact is likely to be protective. The benefits of red palm oil probably come mostly from its minor constituents, i.e. the substances besides its fatty acids. Several studies have shown that a red palm oil extract called palmvitee lowers serum lipids in humans (16, 17). The minor constituents are precisely what are removed during the refining process.

Palm Oil and the Immune System

Red palm oil also has beneficial effects on the immune system in rodents. It protects against bacterial infection when compared with soybean oil (18). It also protects against certain cancers, compared to other oils (19, 20). This may be in part due to its lower content of omega-6 linoleic acid (roughly 10%), and minor constituents.

The Verdict

Yet again, nutritionism has gotten itself into trouble by underestimating the biological complexity of a whole food. Rather than being harmful to human health, red palm oil, an ancient and delicious food, is likely to be protective. It's also one of the cheapest oils available worldwide, due to the oil palm's high productivity. It has a good shelf life and does not require refrigeration. Its strong, savory flavor goes well in stews, particularly meat stews. It isn't available in most grocery stores, but you can find it on the internet. Make sure not to confuse it with refined palm oil or palm kernel oil.


* The approach that Pollan and I favor is a simpler, more empirical one: eat foods that have successfully sustained healthy cultures.

** Some Nigerians are also pastoralists that subsist primarily on dairy.

*** High oleic sunflower oil, from a type of sunflower bred to be high in monounsaturated fat and low in linoleic acid. I think it's probably among the least harmful refined oils. I use it sometimes to make mayonnaise. It's often available in grocery stores, just check the label.

Nitrate: a Protective Factor in Leafy Greens

Cancer Link and Food Sources

Nitrate (NO3) is a molecule that has received a lot of bad press over the years. It is thought to promote digestive cancers, in part due to its ability to form carcinogens when used as a preservative for processed meat. Because of this (1), nitrate was viewed with suspicion and a number of countries imposed strict limits on its use as a food additive.

But what if I told you that by far the greatest source of nitrate in the modern diet isn't processed meat-- but vegetables, particularly leafy greens (2)? And that the evidence linking exposure to nitrate itself has largely failed to materialize? For example, one study found no difference in the incidence of gastric cancer between nitrate fertilizer plant workers and the general population (3). Most other studies in animals and humans have not supported the hypothesis that nitrate itself is carcinogenic (4, 5, 6), but rather that they are only carcinogenic in the context of processed meats due to the formation of carcinogenic nitrosamines. This, combined with recent findings on nitrate biology, has changed the way we think about this molecule in recent years.

A New Example of Human Symbiosis

In 2003, Dr. K. Cosby and colleagues showed that nitrite (NO2; not the same as nitrate) dilates blood vessels in humans when infused into the blood (7). Investigators subsequently uncovered an amazing new example of human-bacteria symbiosis: dietary nitrate (NO3) is absorbed from the gut into the bloodstream and picked up by the salivary glands. It's then secreted into saliva, where oral bacteria use it as an energy source, converting it to nitrite (NO2). After swallowing, the nitrite is reabsorbed into the bloodstream (8). Humans and oral bacteria may have co-evolved to take advantage of this process. Antibacterial mouthwash prevents it.

Nitrate Protects the Cardiovascular System

In 2008, Dr. Andrew J. Webb and colleagues showed that nitrate in the form of 1/2 liter of beet juice (equivalent in volume to about 1.5 soda cans) substantially lowers blood pressure in healthy volunteers for over 24 hours. It also preserved blood vessel performance after brief oxygen deprivation, and reduced the tendency of the blood to clot (9). These are all changes that one would expect to protect against cardiovascular disease. Another group showed that in monkeys, the ability of nitrite to lower blood pressure did not diminish after two weeks, showing that the animals did not develop a tolerance to it on this timescale (10).

Subsequent studies showed that dietary nitrite reduces blood vessel dysfunction and inflammation (CRP) in cholesterol-fed mice (11). Low doses of nitrite also dramatically reduce tissue death in the hearts of mice exposed to conditions mimicking a heart attack, as well as protecting other tissues against oxygen deprivation damage (12). The doses used in this study were the equivalent of a human eating a large serving (100 g; roughly 1/4 lb) of lettuce or spinach.

Mechanism

Nitrite is thought to protect the cardiovascular system by serving as a precursor for nitric oxide (NO), one of the most potent anti-inflammatory and blood vessel-dilating compounds in the body (13). A decrease in blood vessel nitric oxide is probably one of the mechanisms of diet-induced atherosclerosis and increased clotting tendency, and it is likely an early consequence of eating a poor diet (14).

The Long View

Leafy greens were one of the "protective foods" emphasized by the nutrition giant Sir Edward Mellanby (15), along with eggs and high-quality full-fat dairy. There are many reasons to believe greens are an excellent contribution to the human diet, and what researchers have recently learned about nitrate biology certainly reinforces that notion. Leafy greens may be particularly useful for the prevention and reversal of cardiovascular disease, but are likely to have positive effects on other organ systems both in health and disease. It's ironic that a molecule suspected to be the harmful factor in processed meats is turning out to be one of the major protective factors in vegetables.

Pastured Dairy may Prevent Heart Attacks

Not all dairy is created equal. Dairy from grain-fed and pasture-fed cows differs in a number of ways. Pastured dairy contains more fat-soluble nutrients such as vitamin K2, vitamin A, vitamin E, carotenes and omega-3 fatty acids. It also contains more conjugated linoleic acid, a fat-soluble molecule that has been under intense study due to its ability to inhibit obesity and cancer in animals. The findings in human supplementation trials have been mixed, some confirming the animal studies and others not. In feeding experiments in cows, Dr. T. R. Dhiman and colleagues found the following (1):

Cows grazing pasture and receiving no supplemental feed had 500% more conjugated linoleic acid in milk fat than cows fed typical dairy diets.

Fat from ruminants such as cows, sheep and goats is the main source of CLA in the human diet. CLA is fat-soluble. Therefore, skim milk doesn't contain any. It's also present in human body fat in proportion to dietary intake. This can come from dairy or flesh.

In a recent article from the AJCN, Dr. Liesbeth Smit and colleagues examined the level of CLA in the body fat of Costa Rican adults who had suffered a heart attack, and compared it to another group who had not (a case-control study, for the aficionados). People with the highest level of CLA in their body fat were 49% less likely to have had a heart attack, compared to those with the lowest level (2).

Since dairy was the main source of CLA in this population, the association between CLA and heart attack risk is inextricable from the other components in pastured dairy fat. In other words, CLA is simply a marker of pastured dairy fat intake in this population, and the (possible) benefit could just as easily have come from vitamin K2 or something else in the fat.

This study isn't the first one to suggest that pastured dairy fat may be uniquely protective. The Rotterdam and EPIC studies found that a higher vitamin K2 intake is associated with a lower risk of heart attack, cancer and overall mortality (3, 4, 5). In the 1940s, Dr. Weston Price estimated that pastured dairy contains up to 50 times more vitamin K2 than grain-fed dairy. He summarized his findings in the classic book Nutrition and Physical Degeneration. This finding has not been repeated in recent times, but I have a little hunch that may change soon...

Vitamin K2
Cardiovascular Disease and Vitamin K2
Can Vitamin K2 Reverse Arterial Calcification?

Corn Oil and Cancer?

The benefits of corn oil keep rolling in. In a new study by Stephen Freedland's group at Duke, feeding mice a diet rich in butter and lard didn't promote the growth of transplanted human prostate cancer cells any more than a low-fat diet (1).

Why do we care? Because other studies, including one from the same investigators, show that corn oil and other industrial seed oils strongly promote prostate cancer cell growth and increase mortality in similar models (2, 3).

From the discussion section:

Current results combined with our prior results suggest that lowering the fat content of a primarily saturated fat diet offers little survival benefit in an intact or castrated LAPC-4 xenograft model. In contrast to the findings when omega-6 fats are used, these results raise the possibility that fat type may be as important as fat amount or perhaps even more important.

There's a large body of evidence implicating excess omega-6 fat in a number of cancer models. Reducing omega-6 to below 4% of calories has a dramatic effect on cancer incidence and progression*. In fact, there have even been several experiments showing that butter and other animal fats promote cancer growth to a lesser degree than margarine and omega-6-rich seed oils. I discussed that here.


* The average American eats 7-8% omega-6 by calories. This means it will be difficult to see a relationship between omega-6 intake and cancer (or heart disease, or most things) in observational studies in the US or other industrial nations, because we virtually all eat more than 4% of calories as omega-6. Until the 20th century, omega-6 intake was below 4%, and usually closer to 2%, in some traditional societies. That's where it remains in contemporary traditional societies unaffected by industrial food habits, such as Kitava.

Book Review: Dangerous Grains

Dangerous Grains is about the health hazards of gluten grains. It's co-written by James Braly, an M.D. who specializes in food allergies, and Ron Hoggan, a celiac patient who has written widely on the subject.

Celiac disease is a degeneration of the intestinal lining caused by exposure to gluten. Gluten sensitivity is a broader term that encompasses any of the numerous symptoms that can occur throughout the body when susceptible people eat gluten. The term gluten sensitivity includes celiac disease. Gluten is a protein found in wheat, its close relatives (kamut, spelt, triticale), barley and rye. Wheat is the most concentrated source.

Dangerous Grains is a good overview of the mountain of data on celiac disease and gluten sensitivity that few people outside the field are familiar with. For example, did you know:

• An estimated one percent of the U.S. population suffers from celiac disease.


• Approximately 12 percent of the US population may suffer from gluten sensitivity, according to blood antibody tests.


• Gluten can damage nearly any part of the body, including the brain, the digestive tract, the skin and the pancreas. Sometimes gastrointestinal symptoms are absent.
  


• Both celiac and other forms of gluten sensitivity increase the risk of a large number of diseases, such as type 1 diabetes and cancer, often dramatically.


• The majority of people with gluten sensitivity are not diagnosed.


• Most doctors don't realize how common gluten sensitivity is, so they rarely test for it.
  


• Celiac disease and other symptoms of gluten sensitivity are easily reversed by avoiding gluten.

That's an enormous disease burden coming from a single type of food. I suspect the true incidence may actually be higher, although it's difficult to be sure.

Dangerous Grains also discusses the opioid-like peptides released from gluten during digestion. Opioids are powerful drugs, such as heroin and morphine, that were originally derived from the poppy seed pod. They are strong suppressors of the immune system and quite addictive. There are no data that conclusively prove the opioid-like peptides in gluten cause immune suppression or addiction to wheat, but there are some interesting coincidences and anecdotes. Celiac patients are at an increased risk of cancer, particularly digestive tract cancer, which suggests that the immune system is compromised. Heroin addicts are also at increased risk of cancer. Furthermore, celiac patients often suffer from abnormal food cravings. 

I know several people who have benefited greatly from removing gluten from their diets. Anyone who has digestive problems, from gas to acid reflux, or any other mysterious health problem, owes it to themselves to try a gluten-free diet for a month. Gluten consumption has increased quite a bit in the U.S. in the last 30 years, mostly due to an increase in the consumption of processed wheat snacks. I believe it's partly to blame for our declining health. Wheat has more gluten than any other grain. Avoiding wheat and all its derivatives is a keystone of my health philosophy.

Another notable change that Sally Fallon and others have pointed out is that today's bread isn't made the same way our grandparents made it. Quick-rise yeast allows bread to be fermented for as little as 3 hours, whereas it was formerly fermented for 8 hours or more. This allowed the gluten to be partially broken down by the microorganisms in the dough. Some gluten-sensitive people report that they can eat well-fermented sourdough wheat bread without symptoms. I think these ideas are plausible, but they remain anecdotes to me at this point. Until research shows that gluten-sensitive people can do well eating sourdough wheat bread in the long term, I'll be avoiding it. I have no reason to believe I'm gluten sensitive myself, but through my reading I've been convinced that wheat, at least how we eat it today, is probably not healthy for anyone.

I'm not aware of any truly healthy traditional culture that eats wheat as a staple. As a matter of fact, white wheat flour has left a trail of destruction around the globe wherever it has gone. Polished rice does not have such a destructive effect, so it's not simply the fact that it's a refined carbohydrate. Hundreds, if not thousands of cultures throughout the world have lost their robust good health upon abandoning their traditional foods in favor of white flour and sugar. The medical and anthropological literature are peppered with these stories.

Overall, the book is well written and accessible to a broad audience. I recommend it to anyone who has health problems or who is healthy and wants to stay that way!

The Inuit: Lessons from the Arctic

The Inuit (also called Eskimo) are a group of hunter-gatherer cultures who inhabit the arctic regions of Alaska, Canada and Greenland. They are a true testament to the toughness, adaptability and ingenuity of the human species. Their unique lifestyle has a lot of information to offer us about the boundaries of the human ecological niche. Weston Price was fascinated by their excellent teeth, good nature and overall robust health. Here's an excerpt from Nutrition and Physical Degeneration:

"In his primitive state he has provided an example of physical excellence and dental perfection such as has seldom been excelled by any race in the past or present...we are also deeply concerned to know the formula of his nutrition in order that we may learn from it the secrets that will not only aid in the unfortunate modern or so-called civilized races, but will also, if possible, provide means for assisting in their preservation."

The Inuit are cold-hardy hunters whose traditional diet consists of a variety of sea mammals, fish, land mammals and birds. They invented some very sophisticated tools, including the kayak, whose basic design has remained essentially unchanged to this day. Most groups ate virtually no plant food. Their calories came primarily from fat, up to 75%, with almost no calories coming from carbohydrate. Children were breast-fed for about three years, and had solid food in their diet almost from birth. As with most hunter-gatherer groups, they were free from chronic disease while living a traditional lifestyle, even in old age. Here's a quote from Observations on the Western Eskimo and the Country they Inhabit; from Notes taken During two Years [1852-54] at Point Barrow, by Dr. John Simpson:

These people [the Inuit] are robust, muscular and active, inclining rather to spareness [leanness] than corpulence [overweight], presenting a markedly healthy appearance. The expression of the countenance is one of habitual good humor. The physical constitution of both sexes is strong. Extreme longevity is probably not unknown among them; but as they take no heed to number the years as they pass they can form no guess of their own ages.

One of the common counterpoints I hear to the idea that high-fat hunter-gatherer diets are healthy, is that exercise protects them from the ravages of fat. The Inuit can help us get to the bottom of this debate. Here's a quote from Cancer, Disease of Civilization (1960, Vilhjalmur Stefansson):

"They are large eaters, some of them, especially the women, eating all the time..." ...during the winter the Barrow women stirred around very little, did little heavy work, and yet "inclined more to be sparse than corpulent" [quotes are the anthropologist Dr. John Murdoch, reproduced by Stefansson].

Another argument I sometimes hear is that the Inuit are genetically adapted to their high-fat diet, and the same food would kill a European. This appears not to be the case. The anthropologist and arctic explorer Vilhjalmur Stefansson spent several years living with the Inuit in the early 20th century. He and his fellow Europeans and Americans thrived on the Inuit diet. American doctors were so incredulous that they defied him and a fellow explorer to live on a diet of fatty meat only for one year, under the supervision of the American Medical Association. To the doctors' dismay, they remained healthy, showing no signs of scurvy or any other deficiency (JAMA 1929;93:20–2).

Yet another amazing thing about the Inuit was their social structure. Here's Dr. John Murdoch again (quoted from Cancer, Disease of Civilization):

The women appear to stand on a footing of perfect equality with the men, both in the family and the community. The wife is the constant and trusted companion of the man in everything except the hunt, and her opinion is sought in every bargain or other important undertaking... The affection of parents for their children is extreme, and the children seem to be thoroughly worthy of it. They show hardly a trace of fretfulness or petulance so common among civilized children, and though indulged to an extreme extent are remarkably obedient. Corporal punishment appears to be absolutely unknown, and children are rarely chided or punished in any way.

Unfortunately, those days are long gone. Since adopting a modern processed-food diet, the health and social structure of the Inuit has deteriorated dramatically. This had already happened to most groups by Weston Price's time, and is virtually complete today. Here's Price:

In the various groups in the lower Kuskokwim seventy-two individuals who were living exclusively on native foods had in their 2,138 teeth only two teeth or 0.09 per cent that had ever been attacked by tooth decay. In this district eighty-one individuals were studied who had been living in part or in considerable part on modern foods, and of their 2, 254 teeth 394 or 13 per cent had been attacked by dental caries. This represents an increase in dental caries of 144 fold.... When these adult Eskimos exchange their foods for our modern foods..., they often have very extensive tooth decay and suffer severely.... Their plight often becomes tragic since there are no dentists in these districts.

Modern Inuit also suffer from very high rates of diabetes and overweight. This has been linked to changes in diet, particularly the use of white flour, sugar and processed oils.

Overall, the unique lifestyle and diet of the Inuit have a lot to teach us. First, that some humans are capable of being healthy eating mostly animal foods. Second, that some humans are able to thrive on a high-fat diet. Third, that humans are capable of living well in extremely harsh and diverse environments. Fourth, that the shift from natural foods to processed foods, rather than changes in macronutrient composition, is the true cause of the diseases of civilization.

Sunscreen and Melanoma

Melanoma is the most deadly type of skin cancer, accounting for most skin cancer deaths in the US. As Ross pointed out in the comments section of the last post, there is an association between severe sunburn at a young age and later development of melanoma. Darker-skinned people are also more resistant to melanoma. The association isn't complete, however, since melanoma sometimes occurs on the soles of the feet and even in the intestine. This may be due to the fact that there are several types of melanoma, potentially with different causes.

Another thing that associates with melanoma is the use of sunscreen above a latitude of 40 degrees from the equator. In the Northern hemisphere, 40 degrees draws a line between New York city and Beijing. A recent meta-analysis found consistently that sunscreen users above 40 degrees are at a higher risk of melanoma than people who don't use sunscreen, even when differences in skin color are taken into account. Wearing sunscreen decreased melanoma risk in studies closer to the equator. It sounds confusing, but it makes sense once you know a little bit more about UV rays, sunscreen and the biology of melanoma.

The UV light that reaches the Earth's surface is composed of UVA (longer) and UVB (shorter) wavelengths. UVB causes sunburn, while they both cause tanning. Sunscreen blocks UVB, preventing burns, but most brands only weakly block UVA. Sunscreen allows a person to spend more time in the sun than they would otherwise, and attenuates tanning. Tanning is a protective response (among several) by the skin that protects it against both UVA and UVB. Burning is a protective response that tells you to get out of the sun. The result of diminishing both is that sunblock tends to increase a person's exposure to UVA rays.

It turns out that UVA rays are more closely associated with melanoma than UVB rays, and typical sunscreen fails to prevent melanoma in laboratory animals. It's also worth mentioning that sunscreen does prevent more common (and less lethal) types of skin cancer.

Modern tanning beds produce a lot of UVA and not much UVB, in an attempt to deliver the maximum tan without causing a burn. Putting on sunscreen essentially does the same thing: gives you a large dose of UVA without much UVB.

The authors of the meta-analysis suggest an explanation for the fact that the association changes at 40 degrees of latitude: populations further from the equator tend to have lighter skin. Melanin blocks UVA very effectively, and the pre-tan melanin of someone with olive skin is enough to block most of the UVA that sunscreen lets through. The fair-skinned among us don't have that luxury, so our melanocytes get bombarded by UVA, leading to melanoma. This may explain the incredible rise in melanoma incidence in the US in the last 35 years, as people have also increased the use of sunscreen. It may also have to do with tanning beds, since melanoma incidence has risen particularly in women.

In my opinion, the best way to treat your skin is to tan gradually, without burning. Use clothing and a wide-brimmed hat if you think you'll be in the sun past your burn threshold. If you want to use sunscreen, make sure it blocks UVA effectively. Don't rely on the manufacturer's word; look at the ingredients list. It should contain at least one of the following: titanium dioxide, zinc oxide, avobenzone (Parsol 1789), Mexoryl SX (Tinosorb). It's best if it's also paraben-free.

Fortunately, as an external cancer, melanoma is easy to diagnose. If caught early, it can be removed without any trouble. If caught a bit later, surgeons may have to remove lymph nodes, which makes your face look like John McCain's. Later than that and you're probably a goner. If you have any questions about a growth, especially one with irregular borders that's getting larger, ask your doctor about it immediately!