Archive for the ‘low-carbohydrate diet’ Category

MedicineBall*: Harvard School of Public Health steps up to the Plate.

Posted: October 3, 2011 in Dietary Fiber, Evidence Based Medicine, Lipophobes, low-carbohydrate diet, Observational Studies, Protein, The Nutrition Story, Uncategorized, USDA Dietary Guidelines
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First published in October of 2011, this post announced a Q&A on line with Harvard’s Eric Rimm to answer question about the School of Public Health’s new  “Healthy Eating Plate,” its own version of nutritional recommendations to compete with the USDA’s MyPlate. A rather  limited window of one hour  was allotted for the entire country to phone in our questions.  Unfortunately HSPH was not as good at telecommunications as it is at epidemiology and the connection did not start working for a while.  The questions that I wanted to ask, however, still stand and this post is a duplicate of the original with the notice about the Q&A removed.  Harvard has been invited to participate in a panel discussion at the Ancestral Health Symposium, and we will see how these questions can be answered.

— adopted from Pops (at Louder and Smarter), the anonymous brilliant artist and admitted ne’er do well.

One of the questions surrounding USDA Nutrition Guidelines for Americans was whether so-called “sunshine laws,” like the Freedom of Information Act, were adhered to. Whereas hearings were recorded, and input from the public was solicited, there is the sense that if the letter of the law was followed, the spirit was weak.  When I and colleagues testified at the USDA hearings, there was little evidence that their representatives were listening; there was no discussion. We said our piece and then were heard no more.  In fact, at the break, when I tried to speak to one of the panel, somebody came out from backstage, I believe unarmed, to tell me that I could not discuss anything with the committee.

Harvard School of Public Health, home of  “odds ratio = 1.22,” last month published their own implementation of the one size-fits-all approach to public nutrition, the”Healthy Eating Plate.”  Their advice is full of  “healthy,” “packed with” and other self-praise that makes this mostly an infomercial for HSPH’s point of view. Supposedly a correction of the errors in MyPlate from the USDA, it seems to be more similar than different. The major similarity is the disdain for the intelligence of the American public. Comparing the two plates (below), they have exchanged the positions of fruits and vegetables.  “Grains” on MyPlate is now called “Whole Grains,” and “Protein” has been brilliantly changed to “Healthy Proteins.”  How many NIH grants were required to think of this is unknown.  Harvard will, of course, tell you what “healthy” is:, no red meat and, of course watch out for the Seventh Egg.

 

 

 

 

 

 

 

So here are the  questions that I wanted to ask:

  1. Dr. Rimm, you are recommending a diet for all Americans but even within the pattern of general recommendations, I don’t know of any experimental trial that has tested it.  Aren’t you just recommending another grand experiment like the original USDA recommendations which you are supposedly improving on?
  2. Dr. Rimm, given that half the population is overweight or obese shouldn’t there be at least two plates?
  3. Dr. Rimm, I think the American public expects a scientific document.  Don’t you think continued use of the words “healthy,” “packed with nutrients,” makes the Plate more of  an informercial for your point of view?
  4. Dr. Rimm, the Plate site says “The contents of this Web site are not intended to offer personal medical advice,” but it seems that is exactly what it is doing. If you say that you are recommending a diet that will “Lower blood pressure; reduced risk of heart disease, stroke, and probably some cancers; lower risk of eye and digestive problems,” how is that not medical advice?  Are you disowning responsibility for the outcome in advance?
  5. Dr. Rimm, more generally, how will you judge if these recommendations are successful? Is there a null hypothesis? The USDA recommendations continue from year to year without any considerations of past successes or failures.
  6. Dr. Rimm, “healthy” implies general consensus but there are many scientists and physicians with good credentials and experience who hold to different opinions. Have you considered these opinions in formulating the plate? Is there any room for dissent or alternatives?
  7. Dr. Rimm, the major alternative point of view is that low-carbohydrate diets offer benefits for weight loss and maintenance and, obviously, for diabetes and metabolic syndrome. Although your recommendations continually refer to regulation of blood sugar, it is not incorporated in the Plate.
  8. Dr. Rimm, nutritionally, fruits have more sugar, more calories, less potassium, fewer antioxidants than vegetables.  Why are they lumped together? And how can you equate beans, nuts and meat as a source of protein?
  9. Dr. Rimm, looking at the comparison of MyPlate and your Plate, it seems that all that is changed is that “healthy” has been added to proteins and “whole” has been added to grains.  If people know what “healthy” is, why is there an obesity epidemic? Or are you blaming the patient?
  10. Dr. Rimm, you are famous for disagreeing on lipids with the DGAC committee yet your name is on their report as well as on this document is supposed to be an alternative.  Do we know where you stand?
  11. Dr. Rimm, the Healthy Plate “differences” page says “The Healthy Eating Plate is based exclusively on the best available science and was not subjected to political and commercial pressures from food industry lobbyists.” This implies that the USDA recommendations are subject to such pressures.  What is the evidence for this? You were a member of the USDA panel. What pressures were brought to bear on you and how did you deal with them
  12. Dr. Rimm, the Healthy Plate still limits saturated fat even though a study from your department showed that there was, in fact, no effect of dietary saturated fat on cardiovascular disease.  That study, moreover, was an analysis of numerous previous trials, the great majority of which individually showed no risk from saturated fat. What was wrong with that study that allows you to ignore it?

*Medicineball, (colloq) a game that derives from Moneyball, in which an “unscientific culture responds, or fails to respond, to the scientific method ” in order  to stay funded.

The Nutrition Mess. Lessons from Moneyball.

Posted: September 23, 2011 in Evidence Based Medicine, Lipophobes, low-carbohydrate diet, The Nutrition Story
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Baseball is like church. Many attend. Few understand.

— Leo Durocher.

The movie Moneyball provides an affirmative answer to an important question in literature and drama: can you present a scene and bring out the character of a subject that is boring while, at the same time, not make the presentation boring?  The movie, and  Michael Lewis’sbook that it is based on, are about baseball and statistics!  For fans, baseball is not boring so much as incredibly slow, providing a soothing effect like fishing, interspersed with an occasional big catch. The movie stars Brad Pitt as Billy Beane, the General Manager of the Oakland Athletics baseball team in the 1990s.  A remarkably talented high school athlete, Billy Beane, for unknown reasons, was never able to play out his potential as an MLB player but, in the end, he had a decisive effect on the game at the managerial level. The question is how the A’s, with one-third of the budget of the Yankees, could have been in the play-offs three years in a row and, in 2001, could win 102 games.  The movie is more or less faithful to the book and both are as much about organizations and psychology as about sports. The story was “an example of how an unscientific culture responds, or fails to respond, to the scientific method” and the science is substantially statistical.

In America, baseball is a metaphor for just about everything. Probably because it is an experience of childhood and adolescence, lessons learned from baseball stay with us. Baby-boomers who grew up in Brooklyn were taught by Bobby Thompson’s 1951 home-run, as by nothing later, that life isn’t fair. The talking heads in Ken Burns’s Baseball who found profound meaning in the sport are good examples. Former New York Governor Mario Cuomo’s comments were quite philosophical although he did add the observation that getting hit in the head with a pitched ball led him to go into politics.

One aspect of baseball that is surprising, especially when you consider the money involved, is the extent to which strategy and scouting practices have generally ignored hard scientific data in favor of tradition and lore. Moneyball tells us about group think, self-deception and adherence to habit in the face of science. For those of us who a trying to make sense of the field of nutrition, where people’s lives are at stake and where numerous professionals who must know better insist on dogma — low fat, no red meat — in the face of contradictory evidence, baseball provides some excellent analogies.

The real stars of the story are the statistics and the computer or, more precisely, the statistics and computer guys: Bill James an amateur analyzer of baseball statistics and Paul DePodesta, assistant General Manager of the A’s who provided information about the real nature of the game and how to use this information. James self-published a photocopied book called 1977 baseball abstract: featuring 18 categories of statistical information you just can’t find anywhere else. The book was not just about statistics but was in fact a critique of traditional statistics pointing out, for example, that the concept of an “error;” was antiquated, deriving from the early days of gloveless fielders and un-groomed playing fields of the 1850s. In modern baseball, “you have to do something right to get an error; even if the ball is hit right at you, and you were standing in the right place to begin with.” Evolving rapidly, the Abstracts became a fixture of baseball life and are currently the premium (and expensive) way to obtain baseball information.

It is the emphasis on statistics that made people doubt that Moneyball could be made into a movie and is probably why they stopped shooting the first time around a couple of years ago. Also, although Paul DePodesta (above) is handsome and athletic, Hollywood felt that they should cast him as an overweight geek type played by Jonah Hill. All of the characters in the film have the names of the real people except for DePodesta “for legal reasons,” he says. Paul must have no sense of humor.

The important analogy with nutrition research and the continuing thread in this blog, is that it is about the real meaning of statistics. Lewis recognized that the thing that James thought was wrong with the statistics was that they

“made sense only as numbers, not as a language. Language, not numbers, is what interested him. Words, and the meaning they were designed to convey. ‘When the numbers acquire the significance of language,’ he later wrote, ‘they acquire the power to do all the things which language can do: to become fiction and drama and poetry … . And it is not just baseball that these numbers through a fractured mirror, describe. It is character. It is psychology, it is history, it is power and it is grace, glory, consistency….’”

By analogy, it is the tedious comparison of quintiles from the Harvard School of Public Health proving that white rice will give you diabetes but brown rice won’t or red meat is bad but white meat is not, odds ratio = 1.32. It is the bloodless, mindless idea that if the computer says so, it must be true, regardless of what common sense tells you. What Bill James and Paul DePodesta brought to the problem was understanding that the computer will only give you a meaningful answer if you ask the right question; asking what behaviors accumulated runs and won ball games, not which physical characteristics — runs fast, looks muscular — that seem to go with being a ball player… the direct analog of “you are what you eat,” or the relative importance of lowering you cholesterol vs whether you actually live or die.

As early as the seventies, the computer had crunched baseball stats and come up with clear recommendations for strategy. The one I remember, since it was consistent with my own intuition, was that a sacrifice bunt was a poor play; sometimes it worked but you were much better off, statistically, having every batter simply try to get a hit. I remember my amazement at how little effect the computer results had on the frequency of sacrifice bunts in the game. Did science not count? What player or manager did not care whether you actually won or lost a baseball game. The themes that are played out in Moneyball, is that tradition dies hard and we don’t like to change our mind even for our own benefit. We invent ways to justify our stubbornness and we focus on superficial indicators rather than real performance and sometimes we are just not real smart.

Among the old ideas, still current, was that the batting average is the main indicator of a batter’s strength. The batting average is computed by considering that a base-on-balls is not an official at bat whereas a moments thought tells you that the ability to avoid bad pitches is an essential part of the batter’s skill. Early on, even before he was hired by Billy Beane, Paul DePodesta had run the statistics from every twentieth century baseball team. There were only two offensive statistics that were important for a winning team percentage: on-base percentage (which included walks) and slugging percentage. “Everything else was far less important.” These numbers are now part of baseball although I am not enough of a fan to know the extent to which they are still secondary to the batting average.

One of the early examples of the conflict between tradition and science was the scouts refusal to follow up on the computer’s recommendation to look at a fat, college kid named Kevin Youkilis who would soon have the second highest on-base percentage after Barry Bonds. “To Paul, he’d become Euclis: the Greek god of walks.”

The big question in nutrition is how the cholesterol-diet-heart paradigm can persist in the face of the consistent failures of experimental and clinical trials to provide support. The story of these failures and the usurpation of the general field by idealogues has been told many times. Gary Taubes’s Good Calories, Bad Calories is the most compelling and, as I pointed out in a previous post, there seems to have been only one rebuttal, Steinberg’s Cholesterol Wars. The Skeptics vs. the Preponderance of Evidence. At least within the past ten year, a small group have tried to introduce new ideas, in particular that it is excessive consumption of dietary carbohydrate, not dietary fat, that is the metabolic component of the problems in obesity, diabetes and heart disease and have provided extensive, if generally un-referenced, experimental support. An analogous group tried to influence baseball in the years before Billy Beane. Larry Lucchino, an executive of the San Diego Padres described the group in baseball as being perceived as something of a cult and therefore easily dismissed. “There was a profusion of new knowledge and it was ignored.” As described in Moneyball “you didn’t have to look at big-league baseball very closely to see its fierce unwillingness to rethink any it was as if it had been inoculated against outside ideas.”

“Grady Fuson, the A’s soon to be former head of scouting, had taken a high school pitcher named Jeremy Bonderman and the kid had a 94 mile-per-hour fastball, a clean delivery, and a body that looked as if it had been created to wear a baseball uniform. He was, in short, precisely the kind of pitcher Billy thought he had trained the scouting department to avoid…. Taking a high school pitcher in the first round — and spending 1.2 million bucks to sign — that was exactly this sort of thing that happened when you let scouts have their way. It defied the odds; it defied reason. Reason, even science, was what Billy Beane was intent on bringing to baseball.”

The analogy is to the deeply ingrained nutritional tradition, the continued insistence on cholesterol and dietary fat that are assumed to have evolved in human history in order to cause heart disease. The analogy is the persistence of the lipophobes, in the face of scientific results showing, at every turn, that these were bad ideas, that, in fact, dietary saturated fat does not cause heart disease. It leads, in the end, to things like Steinberg’s description of the Multiple risk factor intervention trial. (MRFIT; It’s better not to be too clever on acronyms lest the study really bombs out): “Mortality from CHD was 17.9 deaths per 1,000 in the [intervention] group and 19.3 per 1,000 in the [control] group, a statistically nonsignificant difference of 7.1%”). Steinberg’s take on MRFIT:

“The study failed to show a significant decrease in coronary heart disease and is often cited as a negative study that challenges the validity of the lipid hypothesis. However, the difference in cholesterol level between the controls and those on the lipid lowering die was only about 2 per cent. This was clearly not a meaningful test of the lipid hypothesis.”

In other words, cholesterol is more important than outcome or at least a “diet designed to lower cholesterol levels, along with advice to stop smoking and advice on exercise” may still be a good thing.

Similarly, the Framingham study which found a strong association between cholesterol and heart disease found no effect of dietary fat, saturated fat or cholesterol on cardiovascular disease.  Again, a marker for risk is more important than whether you get sick.  “Scouts” who continued to look for superficial signs and ignore seemingly counter-intuitive conclusions from the computer still hold sway on the nutritional team.

“Grady had no way of knowing how much Billy disapproved of Grady’s most deeply ingrained attitude — that Billy had come to believe that baseball scouting was at roughly the same stage of development in the twenty-first century as professional medicine had been in the eighteenth.”

Professional medicine? Maybe not the best example.

What is going on here? Physicians, like all of us, are subject to many reinforcers but for humans power and control are usually predominant and, in medicine, that plays out most clearly in curing the patient. Defeating disease shines through even the most cynical analysis of physician’s motivations. And who doesn’t play baseball to win. “The game itself is a ruthless competition. Unless you’re very good, you don’t survive in it.”

Moneyball describes a “stark contrast between the field of play and the uneasy space just off it, where the executives in the Scouts make their livings.” For the latter, read the expert panels of the American Heat Association and the Dietary Guidelines committee, the Robert Eckels who don’t even want to study low carbohydrate diets (unless it can be done in their own laboratory with NIH money). In this

“space just off the field of play there really is no level of incompetence that won’t be tolerated. There are many reasons for this, but the big one is that baseball has structured itself less as a business and as a social club. The club includes not only the people who manage the team but also in a kind of women’s auxiliary many of the writers and commentators to follow and purport to explain. The club is selective, but the criteria for admission and retention and it is there many ways to embarrass the club, but being bad at your job isn’t one of them. The greatest offense a club member can commit is not ineptitude but disloyalty.”

The vast NIH-USDA-AHA social club does not tolerate dissent. And the media, WebMD, Heart.org and all the networks from ABCNews to Huffington Post will be there to support the club. The Huffington Post, who will be down on the President of the United States in a moment, will toe the mark when it comes to a low carbohydrate story.

The lessons from money ball are primarily in providing yet another precedent for human error, stubbornness and, possibly even stupidity, even in an area where the stakes are high. In other words, the nutrition mess is not in our imagination. The positive message is that there is, as they say in political science, validator satisfaction. Science must win out. The current threat is that the nutritional establishment is, as I describe it, slouching toward low-carb, doing small experiments, and easing into a position where they will say that they never were opposed to the therapeutic value of carbohydrate restriction. A threat because they will try to get their friends funded to repeat, poorly, studies that have already been done well. But that is another story, part of the strange story of Medicineball.

Portion Control and the Language of Food.

Posted: September 5, 2011 in Dietary Fiber, Intention to Treat, low-carbohydrate diet, The Nutrition Story, USDA Dietary Guidelines
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“Portion Control” is a popular buzz-word in nutrition. It has a serious and somewhat quantitative sound as if it were recently discovered and transcends what it really means which is, of course, self-control. Self-control has been around for long time and has a poor history as a dieting strategy.  Lip service is paid to how we no longer think that overeating means that you are a bad person but “portion control” is just the latest version of the moralistic approach to dieting; the sense of deprivation that accompanies traditional diets may be one of the greatest barriers to success. Getting away from this attitude is probably the main psychological benefit of low-carbohydrate diets.  “Eat all the meat you want” sounds scary to the blue-stockings at the USDA but most people who actually use such diets know that the emphasis is on “want” and by removing the nagging, people usually find that they have very little desire to clean their plate and don’t eat any more meat than they ever did.  Coupled with the satiety of fat and protein compared to carbohydrate, this is surely a major factor in the success of carbohydrate restriction.  In the big comparison trials, the low-fat trials are constrained to fix calories while the low-carbohydrate group is allowed to eat ad-libitum, and the two groups usually come out about the same total calories.

On the other hand, there is an obvious benefit to having a lean and hungry feel if not look and, as Woody Allen might have put it: eating less is good if only for caloric reasons.  So, one tactic in a low carbohydrate diet is to eat a small portion — say, one fried egg, a small hamburger — and then see if you are still hungry before having the second or third portion which while not forbidden, is also not required. The longer you wait between portions, the more satiety sets in.

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Intention-to-treat II: Foster, et al: Weight and Metabolic Outcomes After 2 Years

Posted: August 28, 2011 in Evidence Based Medicine, Intention to Treat, low-carbohydrate diet, The Nutrition Story
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“Doctors prefer large studies that are bad to small studies that are good.”

— anon.

The paper by Foster and coworkers entitled Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet, published in 2010, had a surprisingly limited impact, especially given the effect of their first paper in 2003 on a one-year study.  I have described the first low carbohydrate revolution as taking place around that time and, if Gary Taubes’s article in the New York Times Magazine was the analog of Thomas Paine’s Common Sense, Foster’s 2003 paper was the shot hear ’round the world.

The paper showed that the widely accepted idea that the Atkins diet, admittedly good for weight loss, was a risk for cardiovascular disease, was not true.  The 2003 Abstract said “The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease.” The publication generated an explosive popularity of the Atkins diet, ironic in that Foster had said publicly that he undertook the study in order to “once and for all,” get rid of the Atkins diet.  The 2010 paper by extending the study to 2 years would seem to be very newsworthy.  So what was wrong?  Why is the new paper more or less forgotten?  Two things.  First, the paper was highly biased and its methods were so obviously flawed — obvious even to the popular press — that it may have been a bit much even for the media. It remains to be seen whether it will really be cited but I will suggest here that it is a classic in misleading research and in the foolishness of intention-to-treat (ITT).

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The Office of Research Integrity Conference and the Crisis in Nutrition.

Posted: August 15, 2011 in Lipophobes, low-carbohydrate diet, Research Integrity, The Nutrition Story
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The headline in the BBC News is “Fat ‘disrupts sugar sensors causing type 2 diabetes’” The article does not attribute the quotation in the headline and the first sentence says “US researchers say they have identified how a high-fat diet can trigger type 2 diabetes, in experiments on mice and human tissue.”  Should “mice” or “tissue” have been in the headline?  Should the article itself point out the extent to which mice respond differently, sometimes, oppositely from humans, to high-fat diets?  How strong is the evidence in light of other work?  Is the article altogether prejudicing the reader against fat which is the official position of both private and government health agencies?  The article in question may have some sins of omission but it is certainly restrained if not actually circumspect. The general problem, of course, is whether we get accurate scientific information from the popular media.

Peter Farnham and I and a group of bloggers (Laura Dolszon, Tom Naughton and Jimmy Moore) will speak at the end of the month at a conference produced by the Office of Research Integrity (ORI)) where we will raise several issues in the ethical conduct of current nutritional research. The conference, in general, tries to explore a number of questions on the interaction of science and  society.  The goals are to “discuss the latest research on research integrity…education in the responsible conduct of research; responsible research practices.” While each presenter will have only 15 minutes, this is one of the first times thatd the practices in nutrition with regard to issues of integrity are being addressed.  There are four areas that we will discuss:

Crisis in Nutrition I: The Popular Media and Research Publications

Richard David Feinman, SUNY Downstate Medical Center

Crisis in Nutrition II: Research Integrity in Meeting the Challenge  of Carbohydrate Restriction

Richard David Feinman, SUNY Downstate  Medical Center

Crisis in Nutrition III:  Was the Government Standard Met by the  2010 Dietary Guidelines?

Peter Farnham, Nutrition and Metabolism  Society, Alexandria, VA

Crisis in Nutrition IV:  Vox Populi 

Tom Naughton, Jimmy Moore, Laura Dolson, Independent Writers Franklin TN

The abstract of my first talk is presented below. It is, of course, a tricky area. Within some legal limits, reporters can say what they like.  A researcher speaking in a public venue, personal blog, social media can similarly pretty much sound of as they choose.  Or can they? If they are identified as an expert or are have credentials based on a employment by a prestigious institution, don’t they have to clearly distinguish between opinion and fact? And does the headline have to say that, for example, the high-fat study was done in mice?  All of these are gray areas and motives are hard to discern.  I focussed on one area that seemed more clear cut.  If an experimental study is reported in the media or in a press release from an academic institution (sometimes the same thing), is there an obligation to be sure that any opinions attributed to the investigator derives from that research unless otherwise indicated?

 Crisis in nutrition: I. The popular media and research publications  

Objective:

The public relies on popular media for descriptions of nutrition research.  Of particular interest is carbohydrate-restricted diets, the major challenge to official recommendations.  The goal is to assess the extent to which statements to the media and press releases accurately represent the results of research.

Summary of findings or main points:

Nutrition is an area of great interest to the public but one where matters of scientific fact and policy are contentious. Authors of research papers should sensibly have great freedom in describing of the implications of their research, but have an important role in explaining to the public when that opinion does or does not follow directly from the publication.  Two examples are given of where this is a critical issue. In one, an animal study (Foo, et al. Proc Natl Acad Sci USA 2009, 106: 15418-15423), the accompanying press release implies that it was motivated by observations of patients in a hospital, observations which were purely anecdotal and unsubstantiated.  In a second example, a press release stated that carbohydrate-restricted diets (CRDs) were not included in a comparative study because of their low compliance (Sacks, et al. N Engl J Med 2009, 360: 859-873). No data were given to support this allegation and, it is, in fact not true.  The study concluded that the macronutrient composition of the diet was not important even though, as implemented, dietary intake was the same for the groups studied and, again, the CRD was not included in the study.  It seems likely that that this would have an inhibiting effect on individuals choosing a CRD and represents an important impact of research integrity issues on the community.

Conclusions & recommendations:

Practices where research directly affects the community should be evaluated and guidelines should be generated by academic societies, scientific journals and the popular media. What constitutes appropriate press description of published research should be defined. Reasonable principles are that only those specific conclusions that derive directly from the publication are relevant and authors make clear what is their personal opinion and what is the product of research data.

 Office of Research Integrity

It is important to emphasize that ORI is sponsor of this academic conference and is not related to is regulatory function.  ORI is charged with overseeing federally funded research and emphasizes its role as watchdog in detection and prevention of research misconduct, assisting the Office of the General Counsel (OGC), dealing with suspected retaliation against whistleblowers, and responding to Freedom of Information and Privacy Acts.  Its usual activity involves pinpointing specific fraud.  The website reports, for example, a final judgement against an Assistant Professor at the Boston University School of Medicine Cancer Research Center who published two papers in which he had fabricated data shown as figures in the paper.  He is required to retract the papers and not enter into contracts or sit on advisory panels for two years.

ORI, in general, has the same relation to the research community that Internal Affairs has to the police.  Of course, in research, although there are substantive rewards, blatant fraud is generally pathological: if the results you are falsifying are important, they will surely be repeated and the misbehavior discovered while, if they are not important, the rewards are not likely to be spectacular although, especially these days, keeping your job is desirable.  The suspicion about ORI is also bolstered by their behavior in the Baltimore case in which they were part of the mindless zeal and witch-hunting whose appearance in human interactions seems to have such a low activation energy.

David Baltimore, a Nobel laureate in Physiology or Medicine and, at the time, MIT professor, had co-authored a paper with an immunologist named  Thereza Imanishi-Kari who was accused by a postdoctoral fellow of fabricating data. In the end, nothing came of it but there was much sound and fury and many idiots participated in the tale including the Secret Service (who I was taught were only supposed to protect the President and prosecute counterfeiters). The details of the Baltimore case are well told in capsule form in the Wikipedia entry. Daniel Kevles wrote an outstanding book, at least judged by the first half — the content was too infuriating for me to keep reading.  In any case, after most of the furor had died down, the ORI persisted and found Imanishi-Kari guilty of research misconduct, a ruling overturned by an appeals panel of the Department of Health and Human Services (HHS) which “found that much of what ORI presented was irrelevant, had limited probative value, was internally inconsistent, lacked reliability or foundation, was not credible or not corroborated, or was based on unwarranted assumptions.”  the ORI reputation has probably not recovered from this but it remains one of the few oversight agencies which, at least in nutrition, is sorely needed.

David Baltimore wrote his own description of the events and emphasized that it raise many questions, in particular,  “Who should judge science?” and “How does one distinguish between error and fraud? And does science do an adequate job of policing itself?”  The conference and this blog will discuss these matters which the crisis in nutrition has made of critical importance.  Such philosophical questions were formerly what most of us would have preferred to simply gab about in Starbucks.

Wait a Minute, Lustig. The Threat of Fructophobia. And the Opportunity.

Posted: July 29, 2011 in low-carbohydrate diet
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“The truth?  If I wanted the truth, I would have called Sixty Minutes.”

— Spiros Focás in Jewel of the Nile.

Sugar is an easy target. These days, if you say “sugar” people think of Pop-Tarts® or Twinkies®, rather than pears in red wine or tamagoyaki the traditional sweet omelet that is a staple in Bento Boxes.  Pop-Tarts® and Twinkies® are especially good targets because, in addition to sugar (or high fructose corn syrup (HFCS), they also have what is now called solid fat (the USDA thinks that “saturated” is too big a word for the average American ) and the American Heart Association and other health agencies are still down on solid fat.  Here’s a question, though: if you look on the ingredients list for Twinkies®, what is the first ingredient, the one in largest amount?  (Answer at the end of this post).

The Threat

What went wrong in the obesity epidemic?  There is some agreement that by focussing on fat, the nutritional establishment gave people license to over-consume carbohydrates. The new threat is that by focusing now on fructose, the AHA and USDA and other organizations are giving implicit license to over-consume starch — almost guaranteed since these agencies are still down on fat and protein.  The additional threat is that by creating an environment of fructophobia, the only research on fructose that will be funded are studies at high levels of total carbohydrate where, because of the close interaction between glucose and fructose, deleterious effects are sure to be found. The results will be generalized to all conditions.  Like lipophobia, there will be no null hypothesis.

The latest attack on sugar and on fructose itself (sugar and HFCS are half fructose) comes from Robert Lustig, a pediatrician at University of California San Francisco. His lecture describing fructose as a virtual poison got more than a million and a half hits on YouTube.  The presentation has an eponymous style (Lustig, Ger. adj., merry, amusing, e.g. Die Lustige Witwe, The Merry Widow) and includes a discussion of the science bearing on fructose metabolism. While admitting the limitations of that science, even Gary Taubes was worried. Comments on YouTube and other sites say they liked the science but did not agree with his recommendations — it will turn out that he now wants government control of sugar consumption, especially for my kid and yours.

The presentation of the science is compelling but, while it has a number of important points, it is clearly biased and, oddly, a good deal of it is totally wrong, some of it containing elementary errors in chemistry that border on the bizarre — how hard would it have been to open an elementary organic chemistry text?  In trying to draw parallels between alcohol and fructose, Lustig says “ethanol is a carbohydrate.” Ethanol is not a carbohydrate.  A horse is not a dog. If you said that ethanol is a carbohydrate in sophomore Organic Chemistry, you would get it wrong. Period. No partial credit. Such elementary errors compromise the message and raise the question in what way Lustig is an expert in this field.  It gets worse.

It is biological function that is important and ethanol is not processed like fructose as Lustig says. There is very little chemical sense in saying that ethanol and fructose are processed biologically in similar ways.  And a metabolic pathway is shown in which glycogen is absent. Glycogen is the storage form of glucose and is generally taken as a good thing because of its relation to endurance in athletes but, like fat, glycogen is a storage form of energy and having a lot is not always a good thing.  In any case, it is not true that fructose does not give rise to glycogen.  In fact, fructose is generally better at forming glycogen than glucose is.  This is especially true when you consider the effect of exercise which is why Gatorade® may actually be a good thing if you are in a football game rather than watching one. This is the general error in Lustig’s talk.  Metabolism is not static and has evolved to deal with changing conditions of diet and environment. A metabolic chart, like any map only tells you where you can go, not whether you go there. And the notable absence in Lustig’s talk is data.

It is possible that  sugar and ethanol have behavioral effects  in common but this is not due to similarities in metabolism.  And even the behavioral effects are not settled within the psychology community; alcoholism is far different from “sugar addiction,” if there is such a thing; polishing off the whole container of Häagen-Dazs® may not technically qualify as addictive behavior.

The Threat of Policy

All of this might be okay — Lustig’s lecture was not a scientific treatise — except that he has gone to the next step.  Convinced of the correctness of his analysis, he wants government intervention to control sugar and sweeteners in some way .  There is an obvious sense of deja-vu as another expert attempts to use the American population as Guinea pigs for a massive population experiment, like the low fat fiasco under which we still suffer. It is not just that we got unintended consequences (think margarine and trans-fats) but rather that numerous people have pointed out that the science was never there for low-fat to begin with (brilliantly explained in Fat Head).  In other words leaving aside the question of when we should turn science into policy, is the science any good?

Fructose

It is important to understand that fructose is not a toxin. It is a normal metabolite. If nothing else, your body makes a certain amount of fructose.  Fructose, not music (the food of love), is the preferred fuel of sperm cells. Fructose formed in the eye can be a risk but its cause is generally very high glucose. Fructose is a carbohydrate and is metabolized in ways similar to, if different in detail, from glucose but a substantial amount (can be 60 %) of fructose is turned to glucose — that is why the glycemic index of fructose is 20 and not zero.

The extent to which fructose metabolism has a uniquely detrimental effect is strongly dependent on conditions.  Fructose may be worse than glucose under conditions of very high carbohydrate intake but its effect will change as total carbohydrate is lowered. And since carbohydrate across the board is what is understood to be the problem — Lustig states that clearly in his YouTube — policy would suggest that that is the first line of attack on health — reduce carbohydrate (emphasizing fructose if you like) but as carbohydrate and calories are reduced, any effect of fructose will be minimized.  In the extreme, if you are on a very low carbohydrate diet, any fructose you do eat is likely to be turned into glucose.

The Opportunity

Lustig makes his case against fructose in terms of fundamental biochemistry which is really how it should be.  Can biochemistry be explained to the general population?  Can the problem be explained in a simple but precise way so that we really have the sense of talking about science and not politics?  So what is needed is somebody who actually knows biochemistry.  Maybe somebody with experience in teaching biochemistry to future doctors.  Hey, that’s my job description.  In fact, I’m going to try that in the next few blogs and on YouTube. I and others have  taught courses that try to reduce the three year sequence that professional chemists follow: general chemistry-organic chemistry-biochemistry.  I will try to give everybody a window into organic chemistry, biochemistry and metabolism. In fact, that might be a good focus for government intervention. Instead of punishing the patient, how about funding for teaching biochemistry to the public. For the moment, though, let’s look at some population data.

Sweetener Consumption.

What about sweeteners?  Well, of course, consumption has gone up. Surprisingly, not as much as one would have thought.  According to the USDA about 15 %.  One question is whether this increase is disproportionately due to fructose. The figures below show that, in fact, the ratio of fructose to glucose has remained constant over the last 40 years.  (The deviation from 1:1 which would be expected for pure sucrose or HFCSA, is due to a  relatively constant 20 % or so of pure glucose that  is used in sweetening in the food industry). It is possible that, although the ratio is the same, that the absolute increase in  fructose has a worse effect than the increased glucose but, of course, you would have to prove it.  The figures suggest, however, that you will have to be careful in determining whether the effect of increased sweetener is due to fructose or glucose, or the effect of one on the other, or the effect of insulin and other hormones on both.  An unrestrained, lustige, lack of anything careful is exactly the current threat.

Answer to “puzzler:” The main ingredient in Pop-Tarts® and Twinkies® is flour. Some people say that if you add up the different forms of sugar that will be greater but like all ideas derived from Lustig, there is an advantage in looking at the data: 38 g. of carbohydrate, 17 g. of sugars.

The Warshaw-Diabetes Health Thing – Invitation to Discuss.

Posted: July 8, 2011 in low-carbohydrate diet, The Nutrition Story, USDA Dietary Guidelines
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The whacko suggestion by Hope Warshaw on DiabetesHealth that people with diabetes should increase their carbohydrate intake — I don’t know whether she was serious or just trying to infuriate — obviously generated a rather large response, especially on the DiabetesHealth website itself.  I was writing my own post on the issue when the editor Nadia Al-Samarrie published a piece which seems to have added to the discord. I decided to bypass the argument and I posted the following letter to her suggesting a way to introduce more information and fewer bad vibes.

==============================================================

Dear Nadia,

I understand that publishing a popular site requires one to be provocative and I think you can see that many people had a strong response to Hope Warshaw’s article and your response.  I think you will agree however that this is a serious matter and I want to suggest a mechanism for bringing the science out for the general public.  I am suggesting a discussion between opposing points of view, less a debate that than a presentation of facts although one implementation might be to have a kind of jury of impartial scientists to present summaries.  I would suggest that you and I be organizers and if DiabetesHealth would be one of the sponsors, I feel sure that I would be able to provide other sponsors. It would, of course, be imperative for the American Diabetes Association and the USDA Advisory committee to participate (send or endorse discussants) to establish that recommendations for people with diabetes conform to some kind of “sunshine law.”

The details of such a meeting could be worked out but as a starting point, I would suggest something along the lines of the following.

There would be two panels, one who maintains that a low-carbohydrate diet (definitions to be agreed upon in advance) is the default diet, that is, the one to try first, for both type 1 and type 2 diabetes and metabolic syndrome.  The other would conform to the very restricted view on such diets (only for weight loss, concerns about heart disease or kidney disease or whatever).

There would be, say, four representatives on each panel endorsed, again, by the ADA and USDA, DiabetesHealth and by the Nutrition and Metabolism Society.

Because of the voluminous literature, each side would specify ten papers in the literature, popular writings or book sections (max 30 pages each).  Discussion would be restricted to these sources.

Participants would meet before hand to set up preliminary procedures to avoid a free-for-all or any “defenestration.”

Variations might include a second day in which both panels took questions from the public or press.

I feel sure that such a meeting would go a long way towards reducing the palpable bad feelings and I am sure you agree that the enemy is diabetes and related diseases and not people with other opinions.  I would be glad to discuss, on the phone, how we can get started.

Best Regards,

Richard David Feinman

No Sunshine Down Under: Comments on Larsen, et al.

Posted: June 28, 2011 in Association and Causality, Evidence Based Medicine, Intention to Treat, Lipophobes, low-carbohydrate diet, Observational Studies, The Nutrition Story
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“These results suggest that there is no superior long-term metabolic benefit of a high-protein diet over a high-carbohydrate in the management of type 2 diabetes.”  The conclusion is from a paper by Larsen, et al. [1] which, based on that statement in the Abstract, I would not normally bother to read; it is good that you have to register trials and report failures but from a broader perspective, finding nothing is not great news and just because Larsen couldn’t do it, doesn’t mean it can’t be done.  However, in this case, I received an email from International Diabetes published bilingually in Beijing: “Each month we run a monthly column where choose a hot-topic article… and invite expert commentary opinion about that article” so I agreed to write an opinion. The following is my commentary:

“…no superior long-term metabolic benefit of a high-protein diet over a high-carbohydrate ….” A slightly more positive conclusion might have been that “a high-protein diet is as good as a high carbohydrate diet.”  After all, equal is equal. The article is, according to the authors, about “high-protein, low-carbohydrate” so rather than describing a comparison of apples and pears, the conclusion should emphasize low carbohydrate vs high carbohydrate.   It is carbohydrate, not protein, that is the key question in diabetes but clarity was probably not the idea. The paper by Larsen, et al. [1] represents a kind of classic example of the numerous studies in the literature whose goal is to discourage people with diabetes from trying a diet based on carbohydrate restriction, despite its intuitive sense (diabetes is a disease of carbohydrate intolerance) and despite its established efficacy and foundations in basic biochemistry.  The paper is characterized by blatant bias, poor experimental design and mind-numbing statistics rather than clear graphic presentation of the data. I usually try to take a collegial approach in these things but this article does have a unique and surprising feature, a “smoking gun” that suggests that the authors were actually aware of the correct way to perform the experiment or at least to report the data.

Right off, the title tells you that we are in trouble. “The effect of high-protein, low-carbohydrate diets in the treatment…” implying that all such diets are the same even though  there are several different versions, some of which (by virtue of better design) will turn out to have had much better performance than the diet studied here and, almost all of which are not “high protein.” Protein is one of the more stable features of most diets — the controls in this experiment, for example, did not substantially lower their protein even though advised to do so –and most low-carbohydrate diets advise only carbohydrate restriction.  While low-carbohydrate diets do not counsel against increased protein, they do not necessarily recommend it.  In practice, most carbohydrate-restricted diets are hypocaloric and the actual behavior of dieters shows that they generally do not add back either protein or fat, an observation first made by LaRosa in 1980.

Atkins-bashing is not as easy as it used to be when there was less data and one could run on “concerns.” As low-fat diets continue to fail at both long-term and short-term trials — think Women’s Health Initiative [2] — and carbohydrate restriction continues to show success and continues to bear out the predictions from the basic biochemistry of the insulin-glucose axis  [3], it becomes harder to find fault.  One strategy is to take advantage of the lack of formal definitions of low-carbohydrate diets to set up a straw man.  The trick is to test a moderately high carbohydrate diet and show that, on average, as here, there is no difference in hemoglobin A1c, triglycerides and total cholesterol, etc. when compared to a higher carbohydrate diet as control —  the implication is that in a draw, the higher carbohydrate diet wins.  So, Larsen’s low carbohydrate diet contains 40 % of energy as carbohydrate.  Now, none of the researchers who have demonstrated the potential of carbohydrate restriction would consider 40 % carbohydrate, as used in this study, to be a low-carbohydrate diet. In fact, 40 % is close to what the American population consumed before the epidemic of obesity and diabetes. Were we all on a low carbohydrate diet before Ancel Keys?

What happened?  As you might guess, there weren’t notable differences on most outcomes but like other such studies in the literature, the authors report only group statistics so you don’t really know who ate what and they use an intention-to-treat (ITT) analysis. According to ITT, a research report should include data from those subjects that dropped out of the study (here, about 19 % of each group). You read that correctly.  The idea is based on the assumption (insofar as it has any justification at all) that compliance is an inherent feature of the diet (“without carbs, I get very dizzy”) rather than a consequence of bias transmitted from the experimenter, or distance from the hospital, or any of a thousand other things.  While ITT has been defended vehemently, the practice is totally counter-intuitive, and has been strongly attacked on any number of grounds, the most important of which is that, in diet experiments, it makes the better diet look worse.  Whatever the case that can be made, however, there is no justification for reporting only intention-to-treat data, especially since, in this paper, the authors consider as one of the “strengths of the study … the measurement of dietary compliance.”

The reason that this is all more than technical statistical detail, is that the actual reported data show great variability (technically, the 95 % confidence intervals are large).  To most people, a diet experiment is supposed to give a prospective dieter information about outcome.  Most patients would like to know: if I stay on this diet, how will I do.  It is not hard to understand that if you don’t stay on the diet, you can’t expect good results.  Nobody knows what 81 % staying on the diet could mean.  In the same way, nobody loses an average amount of weight. If you look at  the spread in performance and in what was consumed by individuals on this diet, you can see that there is big individual variation Also, being “on a diet”, or being “assigned to a diet” is very different than actually carrying out dieting behavior, that is, eating a particular collection of food.  When there is wide variation, a person in the low-carb group may be eating more carbs than some person in the high-carb group.  It may be worth testing the effect of having the doctor tell you to eat fewer carbs, but if you are trying to lose weight, you want them to test the effect of actually eating fewer carbs.

When I review papers like this for a journal I insist that the authors present individual data in graphic form.  The question in low-carbohydrate diets is the effect of amount of carbohydrate consumed on the outcomes.  Making a good case to the reader involves showing individual data.  As a reviewer, I would have had the authors plot each individual’s consumption of carbohydrate vs for example, individual changes in triglyceride and especially HbA1c.  Both of these are expected to be dependent on carbohydrate consumption.  In fact, this is the single most common criticism I make as reviewer or that I made when I was co-editor-in chief at Nutrition and Metabolism.

So what is the big deal?  This is not the best presentation of the data and it is really hard to tell what the real effect of carbohydrate restriction is. Everybody makes mistakes and few of my own papers are without some fault or other. But there’s something else here.  In reading a paper like this, unless you suspect that something wasn’t done correctly, you don’t tend to read the Statistical analysis section of the Methods very carefully (computers have usually done most of the work).  In this paper, however, the following remarkable paragraph jumps out at you.  A real smoking gun:

  • “As this study involved changes to a number of dietary variables (i.e. intakes of calories, protein and carbohydrate), subsidiary correlation analyses were performed to identify whether study endpoints were a function of the change in specific dietary variables. The regression analysis was performed for the per protocol population after pooling data from both groups. “

What?  This is exactly what I would have told them to do.  (I’m trying to think back. I don’t think I reviewed this paper).  The authors actually must have plotted the true independent variable, dietary intake — carbohydrate, calories, etc. — against the outcomes, leaving out the people who dropped out of the study.  So what’s the answer?

  • “These tests were interpreted marginally as there was no formal adjustment of the overall type 1 error rate and the p values serve principally to generate hypotheses for validation in future studies.”

Huh?  They’re not going to tell us?  “Interpreted marginally?”  What the hell does that mean?  A type 1 error refers to a false positive, that is, they must have found a correlation between diet and outcome in distinction to what the conclusion of the paper is.  They “did not formally adjust for” the main conclusion?  And “p values serve principally to generate hypotheses?”  This is the catch-phrase that physicians are taught to dismiss experimental results that they don’t like.  Whether it means anything or not, in this case there was a hypothesis, stated right at the beginning of the paper in the Abstract: “…to determine whether high-protein diets are superior to high-carbohydrate diets for improving glycaemic control in individuals with type 2 diabetes.”

So somebody — presumably a reviewer — told them what to do but they buried the results.  My experience as an editor was, in fact, that there are people in nutrition who think that they are beyond peer review and I had had many fights with authors.  In this case, it looks like the actual outcome of the experiment may have actually been the opposite of what they say in the paper.  How can we find out?  Like most countries, Australia has what are called “sunshine laws,” that require government agencies to explain their actions.  There is a Australian Federal Freedom of Information Act (1992) and one for the the state of Victoria (1982). One of the authors is supported by NHMRC (National Health and Medical Research Council)  Fellowship so it may be they are obligated to share this marginal information with us.  Somebody should drop the government a line.

Bibliography

1. Larsen RN, Mann NJ, Maclean E, Shaw JE: The effect of high-protein, low-carbohydrate diets in the treatment of type 2 diabetes: a 12 month randomised controlled trial. Diabetologia 2011, 54(4):731-740.

2. Tinker LF, Bonds DE, Margolis KL, Manson JE, Howard BV, Larson J, Perri MG, Beresford SA, Robinson JG, Rodriguez B et al: Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: the Women’s Health Initiative randomized controlled dietary modification trial. Arch Intern Med 2008, 168(14):1500-1511.

3. Volek JS, Phinney SD, Forsythe CE, Quann EE, Wood RJ, Puglisi MJ, Kraemer WJ, Bibus DM, Fernandez ML, Feinman RD: Carbohydrate Restriction has a More Favorable Impact on the Metabolic Syndrome than a Low Fat Diet. Lipids 2009, 44(4):297-309.

Nothing wrong with Observational Studies. And Association does Imply Causality but…

Posted: June 19, 2011 in Association and Causality, Evidence Based Medicine, Intention to Treat, low-carbohydrate diet, Observational Studies, thermodynamics
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…the association has to be strong and the causality has to be plausible and consistent. And you have to have some reason to make the observation; you can’t look at everything.  And experimentally, observation may be all that you have — almost all of astronomy is observational.  Of course, the great deconstructions of crazy nutritional science — several from Mike Eades blog and Tom Naughton’s hysterically funny-but-true course in how to be a scientist —  are still right on but, strictly speaking, it is the faulty logic of the studies and the whacko observations that is the problem, not simply that they are observational.  It is the strength and reliability of the association that tells you whether causality is implied.  Reducing carbohydrates lowers triglycerides.  There is a causal link.  You have to be capable of the state of mind of the low-fat politburo not to see this (for example, Circulation, May 24, 2011; 123(20): 2292 – 2333).

It is frequently said that observational studies are only good for generating hypotheses but it is really the other way around.  All studies are generated by hypotheses.  As Einstein put it: your theory determines what you measure.  I ran my post on the red meat story passed April Smith  and her reaction was “why red meat? Why not pancakes” which is exactly right.  Any number of things can be observed. Once you pick, you have a hypothesis.

Where did the first law of thermodynamics come from?

Thermodynamics is an interesting case.  The history of the second law involves a complicated interplay of observation and theory.  The idea that there was an absolute limit to how efficient you could make a machine and by extension that all real processes were necessarily inefficient largely comes from the brain power of Carnot. He saw that you could not extract as work all of the heat you put into a machine. Clausius encapsulated it into the idea of the entropy as in my Youtube video.

©2004 Robin A. Feinman

 The origins of the first law, the conservation of energy, are a little stranger.  It turns out that it was described more than twenty years after the second law and it has been attributed to several people, for a while, to the German physicist von Helmholtz.  These days, credit is given to a somewhat eccentric German physician named Robert Julius Mayer. Although trained as a doctor, Mayer did not like to deal with patients and was instead more interested in physics and religion which he seemed to think were the same thing.  He took a job as a shipboard physician on an expedition to the South Seas since that would give him time to work on his main interests.  It was in Jakarta where, while treating an epidemic with the practice then of blood letting, that he noticed that the venous blood of the sailors was much brighter than when they were in colder climates as if “I had struck an artery.” He attributed this to a reduced need for the sailors to use oxygen for heat and from this observation, he somehow leapt to the grand principle of conservation of energy, that the total amount of heat and work and any other forms of energy does not change but can only be interconverted. It is still unknown what kind of connections in his brain led him to this conclusion.  The period (1848) corresponds to the point at which science separated from philosophy. Mayer seems to have had one foot in each world and described things in the following incomprehensible way:

  • If two bodies find themselves in a given difference, then they could remain  in a state of rest after the annihilation of [that] difference if the  forces that were communicated to them as a result of the leveling of  the difference could cease to exist; but if they are assumed to be indestructible,  then the still persisting forces, as causes of changes in relationship,  will again reestablish the original present difference.

(I have not looked for it but one can only imagine what the original German was like). Warmth Disperses and Time Passes. The History of Heat, Von Baeyer’s popular book on thermodynamics, describes the ups and downs of Mayer’s life, including the death of three of his children which, in combination with rejection of his ideas, led to hospitalization but ultimate recognition and knighthood.  Surely this was a great observational study although, as von Baeyer put it, it did require “the jumbled flashes of insight in that sweltering ship’s cabin on the other side of the world.”

It is also true that association does imply causation but, again, the association has to have some impact and the proposed causality has to make sense.  In some way, purely observational experiments are rare.  As Pasteur pointed out, even serendipity is favored by preparation.  Most observational experiments must be a reflection of some hypothesis. Otherwise you’re wasting tax-payer’s money; a kiss of death on a grant application is to imply that “it would be good to look at.…”  You always have to have something in mind.  The great observational studies like the Framingham Study are bad because they have no null hypothesis. When the Framingham study first showed that there was no association between dietary total and saturated fat or dietary cholesterol, the hypothesis was quickly defended. The investigators were so tied to a preconceived hypothesis, that there was hardly any point in making the observations.

In fact, a negative result is always stronger than one showing consistency; consistent sunrises will go by the wayside if the sun fails to come up once.  It is the lack of an association between the decrease in fat consumption during the epidemic of obesity and diabetes that is so striking.  The figure above shows that the  increase in carbohydrate consumption is consistent with the causal role of dietary carbohydrate in creating anabolic hormonal effects and with the poor satiating effects of carbohydrates — almost all of the increase of calories during the epidemic of obesity and diabetes has been due to carbohydrates.  However, this observation is not as strong as the lack of an identifiable association of obesity and diabetes with fat consumption.  It is the 14 % decrease in the absolute amount of saturated fat for men that is the problem.  If the decrease in fat were associated with decrease in obesity, diabetes and cardiovascular disease, there is little doubt that the USDA would be quick to identify causality.  In fact, whereas you can find the occasional low-fat trial that succeeds, if the diet-heart hypothesis were as described, they should not fail. There should not be a single Women’s Health Initiative, there should not be a single Framingham study, not one.

Sometimes more association would be better.  Take intention-to-treat. Please. In this strange statistical idea, if you assign a person to a particular intervention, diet or drug, then you must include the outcome data (weight loss, change in blood pressure) for that person even if the do not comply with the protocol (go off the diet, stop taking the pills).  Why would anybody propose such a thing, never mind actually insist on it as some medical journals or granting agencies do?  When you actually ask people who support ITT, you don’t get coherent answers.  They say that if you just look at per protocol data (only from people who stayed in the experiment), then by excluding the drop-outs, you would introduce bias but when you ask them to explain that you get something along the lines of Darwin and the peas growing on the wrong side of the pod. The basic idea, if there is one, is that the reason that people gave up on their diet or stopped taking the pills was because of an inherent feature of the intervention: made them sick, drowsy or something like that.  While this is one possible hypothesis and should be tested, there are millions of others — the doctor was subtly discouraging about the diet, or the participants were like some of my relatives who can’t remember where they put their pills, or the diet book was written in Russian, or the diet book was not written in Russian etc. I will discuss ITT in a future post but for the issue at hand:  if you do a per-protocol you will observe what happens to people when stay on their diet and you will have an association between the content of the diet and performance.  With an ITT analysis, you will be able to observe what happens when people are told to follow a diet and you will have an association between assignment to a diet and performance.  Both are observational experiments with an association between variables but they have different likelihood of providing a sense of causality.

Metabolic advantage, “a calorie is a calorie,” and why the First Law of Thermodynamics does not apply.

Posted: June 6, 2011 in low-carbohydrate diet, The Nutrition Story, thermodynamics
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The big news in the low carb world is that Consumer Reports has published, for the first time, faint praise for the Atkins diet. However, the vision one might have of CR employees testing running shoes on treadmills doesn’t really apply here. They did not put anybody on a diet, even for a day. They didn’t have to. They have the standards from the government. Conform to the USDA Guidelines and CR will give you thumbs up. It probably doesn’t matter since, these days, most people buy a food processor by checking out the reviews on the internet — there are now many reviews online of what it’s like to actually be on a low-carbohydrate diet, so rather than follow CR’s imaginings of what it’s like, you can check out what users say — Jimmy Moore, Tom Naughton and Laura Dolson together get about 1.5 million posts per month with many tests and best buy recommendations. What caught my eye, though, is the ubiquitous Dean Ornish; the ratio of words written about the Ornish diet to the number of people who actually use it is probably closing in on a googol (as it was originally spelled). The article says: “to lose weight, you have to burn up more calories than you take in, no matter what kind of diet you’re on. ‘The first law of thermodynamics still applies,’ says Dean Ornish, M.D.

That’s how I got into this field. My colleague Gene Fine, and I published our first papers in nutrition on the subject of metabolic advantage and thermodynamics and we gave ourselves credit for reducing the number of people invoking laws of thermodynamics. “Metabolic advantage” refers to the idea that you can lose more weight, calorie-for-calorie on a particular diet, usually a low-carbohydrate diet. (The term was used in a paper by Browning to mean the benefits in lipid metabolism of a low-carbohydrate diet, but in nutrition you can re-define anything you want and you don’t have to cite anybody else’s work if you don’t want to). The idea of metabolic advantage stands in opposition to the idea that “a calorie is a calorie” which is, of course, the backbone of establishment nutrition and all our woe. As in the CR article, whenever the data show that a low-carbohydrate diet is more effective for weight loss, somebody always jumps in to say that it would violate the laws of thermodynamics. Those of us who have studied or use thermodynamics recognize that it is a rather difficult subject — somebody called it the physics of partial differential equations — and we’re amazed at how many experts have popped up in the nutrition field.

Finding the right diet doesn’t require knowing much thermodynamics but it is an interesting subject and so I’ll try to explain what it is about and how it’s used in biochemistry. The physics of heat, work and energy, thermodynamics was developed in the nineteenth century in the context of the industrial revolution — how efficiently you could make a steam engine operate was a big deal.  Described by Prigogine as the first revolutionary science, it has some interesting twists and intellectual connections. The key revolutionary concept is embodied tin the second law which describes the efficiency of physical processes.  It has broad philosophical meaning.  The primary concept, the entropy, is also used in communication and  the content of messages in information theory.  The entropy of a message is, in one context, how much a message has been garbled in transmission.  The history of thermodynamics also has some very strange characters, besides me and Gene, so I will try to describe them too.

First, we can settle the question of metabolic advantage, or more precisely, energy inefficiency. The question is whether all of the calories in food are available for weight gain or loss (or exercise) regardless of the composition of the diet. Right off, metabolic advantage is an inherent property of higher protein diets and low carbohydrate diets. In the first case, the thermic effect of feeding (TEF) is a measure of how many of the calories in food are wasted in the process of digestion, absorption, low-level chemical transformation, etc. TEF (old name: specific dynamic action) is well known and well studied. Nobody disputes that the TEF can be substantial for protein, typically 20 % of calories. It is much less for carbohydrate and still less for fat. So, substituting any protein for either of the other macronutrients will lead to energy inefficiency (the calories will be wasted as heat). A second unambiguous point is that in the case of low-carbohydrate diets, in order to maintain blood glucose, the process of gluconeogenesis is required. You learn in biochemistry courses that it requires a good deal of energy to convert protein (the major source for gluconeogenesis) into glucose.

So, right off, metabolic advantage or energy inefficiency is known and measurable. Critics of carb restriction as a strategy admit that it occurs but say that it is too small in a practical sense to be worth considering when you are trying to lose weight. These are usually the same people who tell you that the best way to lose weight is through accumulation of small changes in daily weight loss by reducing 100 kcal a day or something like that. In any case, there is a big difference between things that are not practical or have only small effects and things that are theoretically impossible. If metabolic advantage were really impossible theoretically, that would be it. We could stop looking for the best diet and only calories would count. Since we know energy inefficiency is possible and measurable, shouldn’t we be trying to maximize it.  But what is the story on thermodynamics? What is it? Why do people think that metabolic advantage violates thermodynamics? What is their mistake? More specifically, doesn’t the first law of thermodynamics say that calories are conserved? Well, there is more than one law of thermodynamics and even the first law has to be applied correctly. Let me explain. (Note in passing that the dietary calorie is a physical kilocalorie (kcal; 1000 calories).

There are four laws of thermodynamics. Two are technical. The zeroth law says, in essence, that if two bodies have the same temperature as a third, they have the same temperature as each other. This sounds obvious but, in fact, it is an observational law — it always turns out that way. The law is necessary to make sure everything else is for real. If anybody ever finds an experimental case where it is not true, the whole business will come crashing down. The third law describes what happens at the special condition known as the absolute zero of temperature. In essence, the zeroth and third laws, allow everything else to be calculated and practical thermodynamics like bioenergetics pretty much assumes it in the background.

The second law is what thermodynamics is really about — it was actually formulated before the first law — but since the first law is usually invoked in nutrition, let’s consider this first. The first law is the conservation of energy law. Here’s how it works: thermodynamics considers systems and surroundings. The thing that you are interested in — living system, a single cell, a machine, whatever, is called the system — everything outside is the surroundings or environment. The first law says that any energy lost by the system must be gained by the environment and any energy taken up by the system must have come from the environment. Its application to chemical systems, which is what applies to nutrition, is that we can attribute to chemical systems, a so-called internal energy, usually written with symbol U (so as not to confuse it with the electrical potential, E). In thermodynamics, you usually look at changes, and the first law says that you can calculate ΔU, the change in U of a system, by adding up the changes in heat added to the system and work done by the system (you can see the roots of thermo in heat machines: we add heat and get work). In chemical systems, the energy can also change due to chemical reactions. Still, if you add up all the changes in the system plus the environment, all the heat, work and chemical changes, the energy is neither created nor destroyed. It is conserved.

Now, why doesn’t the first law apply to nutrition the way Ornish thinks it does? To understand this, you have to know what is done in chemical thermodynamics and bioenergetics, (thermo applied to living systems). If you want to. In nutrition, you can make up your own stuff. But, if you want to do what is done in chemical thermodynamics, you focus on the system itself, not the system plus the environment. So, from the standpoint of chemical thermodynamics, the calories in food represent the heat generated by complete oxidation of food in a calorimeter.



In a calorimeter, the food is placed in a small container with oxygen under pressure and ignited. The heat generated is determined from the increase in temperature of the water bath. (Before the food measurement, we determine the heat capacity of the water bath, that is, how much heat it takes to raise the temperature). The heat is how we define the calories in the food. The box around the sample in the figure shows that we are measuring the heat produced by the system, not the system plus the environment, that is, not applying the first law. If you applied the first law, the calories associated with the food would be zero, because any heat lost in combustion of the food would show up in the water bath of the calorimeter. The calories per gram of carbohydrate would be 0 instead of 4, the calories per gram of fat would be 0 not 9, etc. So, in studying reactions in chemical thermodynamics, energy is not conserved, it is dissipated. When systems dissipate energy, the change is indicated with a minus sign, so for oxidation of food, generally: ΔU < 0. So, no, the first law does not apply. That’s one of the reasons that “a calorie is not a calorie.”
There is an additional point that we assumed in passing. In chemical thermodynamics, the energy goes with the reaction, not with the food. It is not like particle physics where we give the mass of a particle in electron-volts, a measure of energy, because of E=mc2. What this means, practically, is that the 4 kcal per gram of carbohydrate is for the reaction of complete oxidation. Do anything else, make DNA, make protein and all bets are off.
The bottom line is that, contrary to what is usually said, thermodynamics does not predict energy balance and we should not be surprised when one diet is more or less efficient than another. In fact, the question to be answered is why energy balance is ever found. “A calories is a calorie” is frequently what is observed (although there is always a question as to how we make the measurement). The answer is that insofar as there is energy balance, it is a question of the unique behavior of living systems, not physical laws. Two similar subjects of similar age and genetic make-up may, under the right conditions, respond to different diets so that most of what they do is oxidize food and the contributions of DNA or protein synthesis, growth, etc. may be similar and may cancel out so that the major contribution to energy exchange is the heat of combustion.
But thermodynamics is really not about the first law which, while its history is a little odd, it is not revolutionary. Intellectually, the first law is related to conservation of matter. Thermodynamics is about the second law. The second law says that there is a physical parameter, called the entropy, almost always written S, and the change in entropy, ΔS, in any real process, always increases. In ideal, theoretical processes, ΔS may be zero, but it never goes down. In other words, looking at the universe, (any system and its surroundings), energy is conserved but entropy increases. The first law is a conservation law but the second law is a dissipation law. We identify the entropy with the organization, order or information in a system. Systems proceed naturally to the most probable state. In one of the best popular introductions to the subjects, von Baeyer’s Warmth Disperses and Time Passes, entropy is described in terms of the evolution of the organization of his teenage daughter’s room.  To finish up on calorimeters, though, there is Lavoisier’s whole animal calorimeter.



One of Lavoisier’s great contributions was to show that combustion was due to a combination with oxygen rather than the release of a substance, then known as the phlogiston. Lavoisier had the insight that in an animal, the combination of oxygen with food to produce carbon dioxide was the same kind of process. The whole animal calorimeter was a clever way to show this. The animal is placed in the basket compartment f. The inner jacket, b, is packed with ice. The outer jacket, a, is also packed with ice to keep the inner jacket, cold. The heat generated by the animal melts the ice in the inner jacket which is collected in container, Fig 8. Lavoisier showed that the amount of carbon dioxide formed was proportional to the heat generated as it would be if an animal were carrying out the same chemical reactions that occur, for example, in burning of charcoal. “La vie est donc une combustion.” His collaborator in this experiment was the famous mathematician Laplace and people sometimes wonder how he got a serious mathematician like Laplace to work on what is, well, nutrition. It seems likely that it was because Laplace owed him a lot of money.

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