Posts Tagged ‘Good Calories Bad Calories’

I Told George Bray How to do it Right.

Posted: January 19, 2012 in energy metabolism, low-carbohydrate diet, Protein, The Nutrition Story
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“Despite the claims of various diet gurus, excess calorie consumption alone and not the amount of protein in an individual’s diet contributes to the accumulation of unwanted fat….” That’s the tendentious and pretty much inaccurate first line of the press release from JAMA on George Bray’s over-feeding study “Effect of Dietary Protein Content on Weight Gain, Energy Expenditure, and Body Composition During Overeating.”  “Amount of protein?”  What’s going here?  It hasn’t really been about protein.  Most of us “diet gurus” have claimed that carbohydrate, not protein, in the diet was the key macronutrient in regulating metabolism, consistent with the basic biochemistry of the glucose-insulin axis, or as Dr. Bray described Gary Taubes’s position in a review of Good Calories, Bad Calories:

“The problem is the carbohydrates in the diet, their effect on insulin secretion, and thus the hormonal regulation of homeostasis – the entire harmonic ensemble of the human body.”

Reduction in dietary carbohydrate puts increased demands on protein for gluconeogenesis and other processes but the controlling variable is the carbohydrate. The controversy in nutrition has been largely about fat vs carbohydrate.  Should we be on a low-carbohydrate diet or a low-fat diet?

The quotation in the press release says accurately that “Earlier studies in human beings suggested that diets containing either high or low [levels of] protein are less ‘metabolically efficient’ than diets with normal protein levels.”  Accurate, but written as if metabolic efficiency had always been recognized for its importance in weight loss, as if there had not been a dispute over whether the costs of processing protein were important in energy balance, indeed, written as if Bray and coworkers had not maintained that only calories count in weight gain or loss.  The idea of metabolic advantage, that one diet could be more efficient — more weight gained/calorie — has been largely resisted by the nutritional establishment.  Is this slouching toward Metabolic Advantage? (“Who knows not [the Duke] is dead?  Who knows he is?”)

The debate is also about calories.  Should you cut calories or just cut out carbs?  Is it really “excess calorie consumption” and not the effect of excess carbohydrates ? “A calorie is a calorie” or not. Many of the gurus have gone beyond “claiming” to demonstrating that when carbohydrates are low, weight loss is greater than when carbohydrate is high and that the weight loss on a low-carbohydrate diet is primarily in fat stores rather than lean mass.  In head-to-head comparisons, for however long they are compared, low-carbohydrate diets generally out-perform low-fat diets on other parameters as well, glycemic control, the features of atherogenic dyslipidemia. This has been the major challenge to traditional nutrition and the general approach has been to simply ignore this data and dismiss the researchers with innuendo as above.

In some sense, Bray, et al. answered a question that we weren’t asking, but protein is important if more complicated than carbohydrate and fat. So what did the study find? Bray and coworkers compared three diets of 5 %, 15 % and 25 % protein at an excess of calories, that was nominally the same in each group. The study was a random controlled study and was carried out in a metabolic ward so the results are more accurate than the usual diet study that relies on dietary records.  There is something odd about this study, though, in that if you want to say that only calories are the independent variable, you can’t keep calories constant.  What was actually done was to determine the energy requirements for weight maintenance over a run-in period of 2-3 weeks on a maintenance and then an additional 40 % of calories was added.  So although the calories are constant relative to initial energy expenditure, they are not absolutely the same and this is a study of the effect of varying calories while keeping calories constant. The figure below, re-drawn from Figure 6 of the paper comparing intake of absolute energy to protein intake makes you stop and think.

When you have a small number of subjects, a single outlier can bias the results.  If you remove the single highest point (circled in red), the correlation is likely to get much weaker and the normals and low begin to separate.  In other words, the individual variation (the relative efficiency) is sufficient to make it hard to see the effect of variable energy or, perhaps, as the authors themselves set it up, it is energy normalized for baseline that is the key variable.  Then the authors are right (at least by inspection) that the protein intake does not effect the change in body fat but you have only a single value for the energy. In this case, you cannot say “calories alone account for the increase in fat” (Conclusion in Abstract) because you have only a single point.  If you keep constant the variable (carbohydrate) that is most likely to bring out differences, you shouldn’t be surprised in there are no big differences.

Even taking the conclusions at face value, the authors found, as other diet comparison studies have, that weight loss or, in this over-feeding study, weight gain, was not dependent on calories alone: “a calorie is a calorie” not.  It is likely that this was what the study was originally trying to disprove and the results must have been a disappointment.  The way out was that, in this particular case, the differential weight loss showed up in difference in lean mass, rather than in fat mass as has been found in other studies showing variable efficiency.  Since 5 % is very low protein it is probably not surprising that the diet could not provide enough protein for an increase in lean mass this group.

So what are the other diet studies that have found variable efficiency. The reduction in weight found in studies comparing low-carbohydrate diets and low-fat diets not only shows a difference favoring carbohydrate restriction but the improved weight loss is preferentially fat over lean mass. For example, Volek, et al. compared a low fat with a VLCK and the results are as shown below.  In their study, subjects were randomized to one of two hypocaloric diets, a very low-carbohydrate ketogenic (VLCK) diet (carbohydrate <10% of energy) or a low fat (LF) diet and after 8 weeks switched to the other diet. Reported energy was slightly higher during the VLCK but the VLCK group lost more weight and as shown below predominantly in fat, total fat loss, and trunk fat loss for men (despite significantly greater energy intake). The majority of women also responded more favorably to the VLCK diet, especially in terms of trunk fat loss the ratio of trunk fat/total fat was also significantly reduced during the VLCK diet in men and women.  These studies depend on diet recall so are less accurate than the JAMA study but because of the better experimental design, the changes are bigger and with appropriate correction make a less ambiguous case than the JAMA study. The more accurate measurements in the metabolic chamber suggest that individual variation is real and not just due to random error.

So what do we know from Bray, et al.? As described above, there is some ambiguity in what constant energy means. Still, nobody questions that under many conditions, a “calorie is a calorie,” but they actually found that weight gain was different so when metabolic advantage is “claimed” it cannot be dismissed out of hand.  This is different than widely cited studies in the literature that claim macronutrients do not effect weight loss, since if weight gain depends on macronutrient, it is reasonable that weight loss does too.  Similarly, if tissue distribution affects lean mass in this case, then studies where the tissue distribution shows preferential loss of fat can’t be dismissed — again, it is certainly not surprising that a low protein diet will lead to less storage of protein; generally, while it is just as bad a generalization as “a calorie is a calorie,” there is some truth in “you are what you eat.” Also, in the JAMA study, protein was exchanged for fat so a reduction in fat did not have an effect on fat which may or may not be a surprise to many people. Tom Naughton raised a few other questions about Bray, et al. but in the end, the paper reminds me of the joke about the Polish Mafia: they make you an offer you can’t understand.

How to do it.

But  I told George how to do it. A couple of years ago, he and I had a brief correspondence. I made the following proposal. I suggested we could apply for a joint grant and publication to get the answer.  The following is from my email to him in 2008  (I have added some highlights):

 “A modest proposal

 Proponents of carbohydrate-restricted diets (CRD) and critics of such diets cooperate to design a long-term comparison of CRD and low-fat diets.  The groups agree on methods of procedure, make-up of the diets, how compliance will be effected, and what parameters will be measured.

We write the paper first, leaving room for the data, that is, we agree in advance on what the possible outcomes are and what conclusions could be drawn from them.  The final MS can only be edited for language usage. There are no disclaimers, no Monday-morning-quarterbacking, no excuses.

The paper could be submitted while the grant application is being written and would have to be accepted because any objections could be incorporated in the plan.  The grant itself would surely be funded since it incorporates everybody’s specific aims.”

 George hasn’t answered and he obviously has a different approach to the problem but my offer still stands.

In the end, that is what it will take to solve the problem.  Unless we agree on what the question is, how it can be tested and work together to do the experiment, the lipophobes will ignore the low-carbohydrate studies and we will criticize their studies. The real losers, of course, will be the people suffering from obesity and diabetes.  The question everybody always asks me, is why can’t there be a meeting of the minds?  In the current case, why was the JAMA study done?

Why was this study done? 

 “Dr Bray discussed the results with news@JAMA via e-mail.

news@JAMA: What are the practical implications of these findings for patients trying to lose weight or for the physicians trying to counsel them?

 Dr Bray: The first practical implication is an old one: calories count. We showed very clearly that the increase in body fat was due to the increased intake of calories and that the amount of protein in the diet did not change it.

 To avoid that slow weight gain that many adults experience in their middle years, people need to watch their weight and increase activity, decrease food intake, or both; changing the diet alone will not do it.”

This sounds like the the same recommendations we’ve had for years.  Writing this, I suddenly realized that, as they say in German: that’s where the dog is buried.  It is about recommendations.  This research is following the recommendations.  It used to be (should be? assume it must be?) that recommendations follow from the research. Now, it’s the other way around.  Committees make recommendations and then research (sometimes by members of the committee) tries to support the recommendations. Something about this bothers me.

Evidence-based Medicine: Who Decides Admissibility? I. The Frye Standard

Posted: May 6, 2011 in Evidence Based Medicine, The Nutrition Story
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According to the Journal of the American Medical Association (JAMA), the principle of “evidence-based medicine (EBM),” arose in the 1990s [1]. It is widely invoked in the medical literature as a kind of certification that the conclusions of the author are not mere opinions but are backed up by compelling information in biomedical science.  It sounds good. Or does it? It is certainly self-serving and a little bit suspicious, somewhat like Nixon assuring us that he was not a crook.  Evidence based medicine?  What were we doing before?  How was Pasteur able to function in the absence of such an idea?  One thing to think about is that evidence is what is introduced into courts of law.  But not all evidence is admissible. A judge decides what is admissible and there are many precedents, in particular, on what constitutes scientific evidence in a legal proceeding.

EBM relies on a hierarchy of levels of evidence (e.g. Table 1) with the random controlled trial (RCT) as the highest and expert opinion as the lowest.  Recommendations from health agencies and awarding of research grants are frequently justified on conformity to EBM or at least on their placing primary importance on RCTs.

Evidence from the USDA

Early in 2011, the USDA released its 2010 Dietary Guidelines for Americans [2].  With the dates suggesting the backward-looking nature of the Guidelines, they were nonetheless based on the Report of a prestigious committee (DGAC) [3] who, in turn, made much of their reliance on a new Nutrition Evidence Library (NEL). I and my colleagues were invited to submit a critique of the Report by the journal Nutrition. The editor, Michael Meguid indicated that the journal wanted a balanced report, pros and cons.  I called Dr. Meguid:

RDF: You know, the report is not particularly balanced. I’m not sure how you write a balanced review of an unbalanced report.

MM:  You can make the critique as strong as you like as long as you carefully document everything. But what’s your main problem with the Report?

RDF: Well, it makes very strong recommendations in the face of contradictory evidence.

MM: Make that the title of your article.

So we wrote an article called “In the face of contradictory evidence: Report of the Dietary Guidelines for Americans Committee” [4]. The journal was kind enough to make it an open access article and it’s available on this blog. In the end, on titles, we were one-upped by Steven Malanga, whose article in the New York Post was called “Fed’s Food Fog.”

For sure, both the Report and the final Guidelines were the proverbial camel-like production of a committee, tedious, repetitive and stylistic dreadful.  But what about the NEL?  What about the evidence?  Style aside, wasn’t this evidence based medicine?

Where do these guidelines come from? The assumption is that evidence follows its etymologic roots, stuff that is visible, stuff that comes from the sensible and true avouch of our own eyes. In fact, it is most often applied, as in the case of the DGAC, to the most controversial and contentious subjects. Calling something evidence is not enough. So what happens in courts of law? In a court of law, a judge decides on whether the jury can hear the evidence.  Who decides admissibility of the evidence in EBM?

Conflict resolution in science.

Science is a human activity. Conflict, controversy and a resistance to new ideas are well known even in the so-called hard, that is, more mathematical, sciences, and even where there are no outside forces as there was in the case of Galileo.  In the twentieth century, conflicts do not generally impede progress for long. Especially in the physical sciences, there is usually agreement on basic assumptions and on the rules of logic, allowing ultimate acceptance of strong evidence. Competing theories may coexist and supporters of both are likely to admit that they are awaiting reconciliation.

What happens when the spontaneous process of conflict resolution in science breaks down?  What happens in conditions where scientific disagreement is strong and a majority position becomes so dominant that it controls the funding and publication of scientific work and can ignore or repress contradictory evidence and repress exposition of alternative theories.  In essence, how do we deal with a recapitulation of the case of Galileo?

There is no system to decide on the admissibility in the cases considered by EBM.   I am not the first person to point out that EBM is largely the position of experts on one side of a scientific conflict [5], the lowest level of evidence on traditional EBM scales (e.g. “Level III: Opinions of respected authorities… of the US Preventive Services Task Force Systems,” Table 1).  EBM is sustained by those who want to use its particular criteria but these have never been subjected to outside affirmation.

In this situation, where science cannot police itself, we have to look for some outside guidance.  What do the courts do?  As one would expect there, is a long and extensive history of the legal system’s  attempt to deal with what constitutes scientific evidence.  On the chance that the legal perspective may help, I will discuss some of the issues.

Frye and the need for rules.

A key decision in the history of science in the courts is Frye v. United States.  In 1923, a Federal Appeals court ruled that the opinions of experts have to be supported by a scientific community. Frye had been convicted of second-degree murder but appealed on the grounds that he had successfully passed a lie-detector test.  At that time the device was a simple blood pressure machine and an expert witness testified as to the results. The court ruled that the lie-detector test “has not yet gained such standing and scientific recognition among physiological and psychological authorities as would justify the courts in admitting expert testimony‚” affirming the judgment of the lower court.

The ruling in Frye gave rise to the idea of “general acceptance,” and, by analogy, this appears to be the main principle in the admissibility of evidence in the nutrition world.  Sufficiently well established that it could be included in a biochemistry text is the idea that “consumption of saturated fats is positively associated with high levels of total plasma cholesterol and LDL cholesterol and an increased risk of CHD”[6] Known to students as “the Lippincott Book,” Harvey and Ferrier is the best selling biochemistry book in the world and it is correct when it states “Most experts strongly advise limiting intake of saturated fats.”

Most, but not all.  A small but not insignificant minority hold otherwise and whereas they agree that dietary saturated fat may raise blood cholesterol, they can provide overwhelming evidence that it is not associated with cardiovascular disease. This has been demonstrated in almost every large trial.

The problem is described in Marcia Angell’s Science on Trial [7].  Angell explains that Frye was not without its critics ([7], page 126).  Opponents, she wrote,

“claimed somewhat improbably, that it would tend to exclude novel, far-sighted testimony by modern-day Galileos. There is no record of this happening once, let alone often.  Furthermore, even if a modern-day Galileo did not make into court at first, that fact should not stop him from prevailing in the scientific community.  Courts do not determine scientific acceptance, as implied by the argument that we need to keep our courts open to the hidden Galileos in our midst.”

But isn’t this exactly what has happened in nutrition and maybe, in general, in the medical community?  The “experts” control editorial boards, granting agencies and academic departments and are as powerful as the Catholic Church in repressing dissent.  They have prestige and, in many cases, undisputed accomplishments, but does science run on general acceptance? Does majority (of experts) rule?

One of the problems with Frye that lawyers have addressed is a question of identifying the field of academic or scientific field in which the general acceptance is to be considered.  Different disciplines hold to different standards.  In the case at hand, many ideas in nutrition would be dismissed out of hand by biochemists. Many methodologies would be considered absurd by physical scientists: Intention-to-treat is perhaps the most absurd.  It has been pointed out that the question of who is an expert might have applied to the techniques in the original Frye case, at least as it might be implemented today: “If polygraph examiners are selected as the relevant field, polygraph results would be admissible.” (http://law.jrank.org/pages/2006/Scientific-Evidence-Frye-v-United-States.html).

The epidemic of obesity and diabetes stands as a testament to the failure of the experts.  A small library can be assembled of books attacking establishment medical nutrition. Uffe Ravnskov’s classic Cholesterol Myths is updated in Ignore the Awkward. Gary Taubes’s recent Good Calories, Bad Calories is the most compelling and James Le Fanu’s Rise and Fall of Modern Medicine, the most succinct but just sitting at my desk now I can see a dozen others on the book shelf.  Surprisingly, there has been only one rebuttal, Steinberg’s Cholesterol Wars, the subject of the next post .

Table 1.  Examples of Levels of Evidence from Various Sources. 

US Preventive Services Task Force Systems for ranking evidence about the effectiveness of treatments or screening:

Level I: Evidence obtained from at least one properly designed randomized controlled trial.

Level II-1: Evidence obtained from well-designed controlled trials without randomization.

Level II-2: Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group.

Level II-3: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.

Level III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

Bibliography

1. Torpy JM, Lynm C, Glass RM: JAMA patient page. Evidence-based medicine. JAMA 2009, 301(8):900.

2. Dietary Guidelines for Americans, 2010 [http://www.dietaryguidelines.gov.]

3. US Department of Agriculture and US Department of Health and Human Services: Report of the Dietary Guidelines Advisory Committee on the dietary guidelines for Americans, 2010. June 15, 2010. In.; 2010.

4. Hite AH, Feinman RD, Guzman GE, Satin M, Schoenfeld PA, Wood RJ: In the face of contradictory evidence: report of the Dietary Guidelines for Americans Committee. Nutrition 2010, 26(10):915-924.

5. Marantz P, Bird E, Alderman M: A Call for Higher Standards of Evidence for Dietary Guidelines. Am J Prev Med 2008, 34(3):234-239.

6. Harvey R, Ferrier D: Biochemistry, 5th edn. Baltimore and Philadelphia: Lippincott Williams & Wilkins; 2011.

7. Angell M: Science on Trial. New York: W. W. Norton & Co.; 1996.