Posts Tagged ‘nutrition’

Stone-walling low-carb: DAA, AHPRA, and the Diet of Worms.

Posted: March 3, 2017 in American Diabetes Association
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Our 2015 paper, Low-carbohydrate diets as the first approach in the treatment of diabetes. Review and evidence-base, summarized the clinical experience and the research results of the 26 authors. Meant to be a kind of manifesto on theory and practice, the first version of the manuscript was submitted to a couple of major journals under the title “The 15 Theses on…” harking back to Martin Luther’s 95 Theses. A critique of Church practices, particularly indulgences — for a few bucks, we get you or your loved ones out of purgatory — the Theses were supposed to have been nailed by Luther to the door of a church in Wittenberg. Our MS was rejected by BMJ and New England Journal although, like the original 95, it did not seem particularly radical — The American Diabetes Association (ADA) acknowledges that dietary carbohydrate is the major source of high blood glucose and most of our points of evidence were based on pretty solid fact.  Anyway, somebody suggested that we were, in effect, trying to nail our low-carbohydrate paper to the door of the ADA and, in the end, we changed the name to “evidence base” and it was ultimately published.

Until recently, I had not noticed the extensive parallels of the current low-carbohydrate revolution with the Protestant Reformation. The recent imperious and rather savage actions of professional organizations, notably two in Australia, the DAA (Dietitian’s Association of Australia) and AHPRA (Australian Health Practitioner Regulation Agency) in clamping down on their own members for deviation from orthodoxy brought out the similarities. Unlike Luther, who felt that the church really needed his help in getting abuses straightened out, Jennifer Elliott, a dietitian with an established practice of 30 years and Gary Fettke an orthopedic surgeon, thought that they were just doing their job and that, however, non-standard, the low-carbohydrate diets that they recommended for people with diabetes, was far from heresy. Because of the ties between government health agencies, Jennifer ultimately lost her job and Gary is under the bizarre order not to recommend diets to his patients because, as an orthopedic surgeon, there is “nothing associated with your medical training or education that makes you an expert or authority in the field of nutrition, diabetes or cancer.” (Those of us who are actively trying to upgrade the medical curriculum would question which part of the medical profession has such expertise or authority). Dr. Fettke’s training does, however, allow him to perform amputations which have diabetes as its greatest cause, second only to accidents. In any case, offering low-carbohydrate diets to patients has long been perceived as a threat by establishment medicine.  While their claims that they, and they alone, can control the epidemics of obesity and diabetes has been at the level of offering reduction of time in purgatory.  The medical establishment has been intolerant of criticism but has largely responded by delaying or preventing publication and by refusing to fund research that might get the “wrong” answer. The direct attacks on practitioners is new. There are several instances but the Australian cases distinctly represent desperation.

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Luther at the Diet of Worms.

History of religion remains one of the gaps in my undergraduate liberal education and I was unfamiliar with the dramatic events surrounding Luther’s mission. The sixteenth century was a brutish time and I should have guessed how violent and oppressive would have been the response of the Catholic Church to Luther’s suggestions for improvement. After all, if you insisted on the word of the Bible rather than the word of priests, indeed, if you wanted direct access to a Bible in your own language rather than in Latin, then everybody could be their own savior. Being burnt at the stake was standard punishment for such heresy. We all know about Galileo’s brutal treatment and his being forced to recant his heliocentric theories, although at some point, he supposedly muttered, under his breath, “eppur se muove.” (It (the earth) does move anyway). That was almost a century after Luther’s protest and the danger was even greater in 1521. Luther, however, was a madman and refused to recant. Ultimately, he faced a trial at the Diet of Worms. (Contrary to popular opinion, “Diet” is an English word and means assembly; the German is Reichstag; Worms is in Germany, about 60 kilometres from Frankfurt-am-Main, and is pronounced “Vorms,” to rhyme with “norms,” but the joke is widely made, even by Shakespeare: see end of this post). At The Diet, Luther got off because a unanimous vote was required for conviction. He had an inside man, Frederick the Wise, the elector (as local political leaders were known) in his province.  Frederick seems to have thought that Luther was good for tourism (and probably helped get the Church off his own back). Of course,“not guilty,” doesn’t mean innocent and, as for sex-offenders in our day, you could get killed in the street anyway and the authorities would understand. To protect him, Frederick had Luther “kidnapped,” disguised as an aristocrat with the alias Junker Jörg and he went to the mattresses in a Castle in Wartburg for a year until it all blew over. Lucas Cranach the Elder painted a portrait of Jörg, possibly to let followers know that Luther was still alive.

575707-1449742854         Junker Jörg aka Martin Luther.

Heresy down under

So what had the Australian health professionals done to arouse the wrath of the “Church”? Not much. Jennifer Elliott has more than 30 years of experience and is the author of the excellent book, Baby Boomers, Bellies & Blood Sugars  which is distinguished by its straight-forward practical approach and does not seem to tweak anybody’s beard. In fact, she was not really accused of any specific thing although the message was clear: low-carbohydrate high fat (LCHF) diets are forbidden. Trying to help out, I sent an email message to Claire Hewat, head of DAA. I attached the twelve-points of evidence paper and I explained our position. I pointed out that “Ms. Elliott seems quite upset and genuinely puzzled since carbohydrate restriction has been a treatment for diabetes more or less forever, certainly going back to Elliott Joslin (early twentieth century physician and authority on diabetes).”

hewat_claire11474634995-300x224        Claire Hewat, head of DAA.

I mentioned an interview with a reporter from the New York Times who could not understand the resistance to an established, successful and ultimately obvious therapy — you don’t give carbohydrates to people with a disease of carbohydrate intolerance — and I made the case that the burden of proof should be on anyone who didn’t approve. I suggested a discussion, “perhaps an online webinar, in which all sides present their case. I and/or my colleagues would be glad to participate.” Claire’s answer was that I was “obviously not in possession of all the facts in this matter, nor can I apprise you of them as this is part of a confidential complaints process …nor is DAA afraid of debate but this is not the place for it.”

Not to digress too much, I loved the idea that I did not have the facts right but the facts were not available because they were confidential. It reminded me of watching a scene in one of the old Basil Rathbone Sherlock Holmes movies. Holmes is playing the violin and his arch-enemy, Professor Moriarity suddenly appears in the doorway:

Moriarity: “Holmes, I’ve come to….Well, I am sure that you can deduce why I’ve come.”

Holmes: “Yes. And I’m sure you can deduce my answer.”

Moriarity: “So that’s final?”

Holmes: “I’m afraid so.”

Most distressing remains the fact that DAA constitutes a professional dietitians’ organization which should, as in Macbeth, “against his murderer shut the door, / Not bear the knife myself.” (Is this a DAAger I see before me?)

The details of Jennifer’s case are buried in evasive legal double-talk but the precipitating events make it clear that censure derives from her recommending low-carbohydrate diets to her patients with diabetes. Claire Hewat’s defense against this obvious lack of due process was that Jennifer was invited to appear before an inquiry, set up somewhat along the lines of the Diet of Worms, but Jennifer refused to appear. In fact, it would have been worse than the Diet in that there were no formal charges and even Luther had been afforded legal representation. There would certainly be no defenders, as Luther had in Frederick, the Wise. Most important, recanting was not an option — if it wasn’t about anything real, there was nothing to recant. (Like Luther, she probably would not have felt able to recant anyway). Jennifer declined to attend telling Claire that it appeared to be “an invitation to a beheading.” The net effect is that she lost her job and and legal recourse would likely be exorbitant.

The words

In the reformation, heresy might have meant simply owning a Bible in your native language, or really owning any Bible at all. The Church held onto the Latin versions which you did not get to see directly. Somewhat like governmental nutritional guidelines in our tme, it was not in your native language, and required an “expert” priest to tell you what’s what. The first English translation was accomplished by John Wycliffe and during the English Reformation, several people were actually executed for owning a Wycliffe Bible. I found it somewhat analogous to the persistent hatred of Dr. Atkins so long after his death, that, at some point, the Church in England had Wycliffe’s body exhumed and burnt at the stake.

Ultimately, Luther succeeded because of Gutenberg and the invention of movable type. Now you did not have to make copies by hand. Now Luther could really get the word out. And he wrote the word. During his period of lying low in Wartburg, he translated the Bible into German.  And he published it. It was a big hit although the German population recognized that they had been swindled — financially as well as theologically — and history records a Peasant’s Revolt which was put down with great brutality. We recognize in all this parallels to what is really going on in the establishment’s determination to repress LCHF diets. And everybody recognizes the analog of Gutenberg’s press.

Unser Gutenberg  and the Fettke case

Our Gutenberg is, of course, the internet where technical and scientific writings, once the province of specialists, can now be viewed by many and where they can be discussed widely. Publishers of many journals try to maintain pay-walls in keeping with somebody’s observation that publishers’ function used to be to make new information available while now they work to make information unavailable.  (Many simultaneously cash in on open access which charges the authors outrageous fees). Whether the availability of scientific facts is out-weighed by proliferation of alternative facts is open to question but, on balance, we have a view, not only of the science, but of the inner workings of the health agencies that might otherwise be visible to only a few. And that’s how we have extensive access to the Fettke case and an associated Diet convened by the Australian Senate.

As reported by Marika Sboros, Fettke “cannot tell patients not to eat sugar. Why not? Because the country’s medical regulatory body, Australian Health Practitioners Regulatory Authority (AHPRA), says so….It has been investigating Fettke for more than two years now. That was after the first anonymous complaint from a DAA dietitian in 2014. Earlier this year,  AHPRA told Fettke to stop talking about nutrition until it had decided on a suitable sanction.” and — I’m not making this up — “informed Fettke that it was investigating him for ‘inappropriately reversing (a patient’s) type 2 diabetes…’”

Dr. Gary Fettke testified at an Australian Senate Inquiry on November 1. and just “by coincidence,” a few hours later, AHPRA’s 2 1/2 year investigation came to an end and Fettke was told that he would be constrained from giving nutritional advice.  In the end, this did not sit well with the Senate which undertook further hearing interrogating Martin Fletcher, the CEO of APHRA.

“Haven’t you got better things to do?”

You can see Martin Fletcher trying to defend AHPRA’s actions.  on Youtube. At 31:25, one of the Senators asked “…if a health practitionerr is advising a patient to go on a … sensible, medically-accepted diet program, why would you risk-assess that and have all guns blazing? Haven’t you got better things to do?”

One of life’s great disappointments is that when you finally corner the bad guys, they turn out to be pathetic like Saddam Hussein. They don’t break down on the stand as in the old Perry Mason episodes. It is sad but it is also hard to feel much sympathy.

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Martin Fletcher, CEO of AHPRA trying to juggle the truth at the Senate hearing.

“Bread thou art…”

It was a trip to Rome, intended to deepen his faith, that ultimately contributed to Luther’s transformation. He saw corruption on a grand scale but what really freaked him out was that corruption and vice were coupled with a cynical disregard for religious practice. A priest going through the motions of giving the elements in the sacrament  muttered to himself “Bread thou art, and bread thou shalt remain; wine thou art, and wine thou shalt remain.”

That becomes the most distressing feature of this analogy. The quotation above, “There is nothing associated with your medical training or education that makes you an expert or authority in the field of nutrition, diabetes or cancer,” comes from a letter to Dr. Fettke that continued “Even if, in the future, your views on the benefits of the LCHF lifestyle become the accepted best medical practice, this does not change the fundamental fact that you are not suitably trained or educated as a medical practitioner to be providing advice or recommendations on this topic as a medical practitioner.”

This statement that treating disease is less important than loyalty to political power stands as the greatest exposition of the need for Reformation in Medicine.

Appendix. Shakespeare on the Diet of Worms.

Hamlet has been charged by his father’s Ghost with avenging the father’s murder by Claudius, the current king. Hamlet has put on an “antic disposition” to hide his motives. At one point, mistaking him for the King, Hamlet kills Polonius, a pompous court official, who is hiding behind a wall-hanging. The king hears about it and is pissed and wants to know where the body is (Act 4,Scene 3):

CLAUDIUS: Where’s Polonius?

HAMLET: At supper.

CLAUDIUS: At supper where?

HAMLET: Not where he eats, but where he is eaten. A certain convocation of politic worms are e’en [now] at him. Your worm is your only emperor for diet. We fat all creatures else to fat us, and we fat ourselves for maggots. Your fat king and your lean beggar is but variable service—two dishes, but to one table. That’s the end.

CLAUDIUS: Alas, alas!

HAMLET: A man may fish with the worm that hath eat of a king, and eat of the fish that hath fed of that worm.

CLAUDIUS: What dost thou mean by this?

HAMLET: Nothing but to show you how a king may go a progress through the guts of a beggar.

CLAUDIUS: Where is Polonius?

HAMLET: In heaven. Send hither to see. If your messenger find him not there, seek him i’ th’ other place yourself. But if indeed you find him not within this month, you shall nose him as you go up the stairs into the lobby.

CLAUDIUS (to attendants) Go seek him there.

(Exeunt some attendants)

HAMLET: He will stay till ye come.

Ketogenic Diets for Cancer III. More background and the Warburg Effect.

Posted: December 4, 2016 in Cancer, Cell Signaling, energy metabolism, gluconeogenesis, glycolysis, ketogenic diet, low-carbohydrate diet, Warburg effect
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This series of posts is a followup to the project that Dr. Eugene Fine and I described in our campaign at Experiment.com. as follow-up to Dr. Fine’s pilot study of ten advanced cancer patients on ketogenic diets and the in vitro projects that we are carrying out in parallel.

The last post described the two major processes in energy metabolism, (anaerobic) glycolysis and respiration. Pyruvate is the product of glycolysis and has many fates. (Remember pyruvate and pyruvic acid refer to the same chemical). For cells that rely largely on glycolysis, pyruvate is converted to several final products like ethanol, lactic acid and a bunch of other stuff that microorganisms make in the fermentation of glucose. (The unique smell of butter, e.g., is due to acetoin and other condensation products of pyruvate). Rapidly exercising muscles also produce lactic acid.

The sudden interest in the metabolic approach to cancer stems from the work of Otto Warburg whose lab in the 1930’s was a center for the study of metabolism. (Hans Krebs was an Assistant Professor in the lab). Warburg’s landmark observation was that cells from cancer tissue showed a higher ratio of lactate to CO2 than normal cells, that is, the cancerous tissue was metabolizing glucose via glycolysis to a greater degree than normal even though oxygen was present. The Coris (Carl and Gerty of the Cori cycle) demonstrated what is now called the Warburg effect in a whole animal. Ultimately, Warburg refined the result by comparing the ratio of lactate:CO2 in a cannulated artery to that in the vein for a normal forearm muscle. He compared that to the ratio in the forearm of the same patient  that contained a tumor. Warburg claimed that this greater dependence on glycolysis was a general feature of all cancers and for a long time it was assumed that there was a defect in the mitochondrion in cancer cells. These are both exaggerations but aerobic glycolysis appears as a feature of many cancers and defects in mitochondria, where they exist, are more subtle than gross structural damage. The figure shows current understanding of the Warburg Effect.

kdforca_blog_iii_warburg_figure

What about this mechanism makes us think that  ketone bodies are going to be effective against cancer? We need one more step in biochemical background to explain what we think is going on. In normal aerobic cells, pyruvate is converted to the compound acetyl-CoA.  Acetyl-CoA represents another big player in metabolism and functions as the real substrate for aerobic metabolism. If you have taken general chemistry, you will recognize acetyl-CoA as a a derivative of acetic acid.

The reaction acetyl-CoA ➛ 2CO2 is the main transformation from which we get energy. Acetyl-CoA provides the building block for fatty acids and for ketone bodies. Conversely, fatty acids are a fuel for cells because they can be broken down to acetyl-CoA. Under conditions of starvation, or a low-carbohydrate diet, the liver assembles 2 acetyl-CoA’s to ketone bodies (β-hydroxy butyrate and acetoacetyl-CoA). The ketone bodies are transported to other cells where they are disassembled back to acetyl-CoA and are processed in the cell for energy. The liver is a kind of metabolic command center and ketone bodies are a way for the liver to deliver acetyl-CoA to other cells.kdforca_blog-iii_dec_4

Now we are at the point of asking how a cell knows what to do when presented with a choice of fuels? In particular, how does the input from fat dial down glycolysis so that pyruvate, which could be used for something else (in starvation or low-carb, it will be substrate for gluconeogenesis), is not used to make acetyl-CoA.  It turns out that acetylCoA (that is, fat or ketone bodies) regulate their own use by feeding back and directly or indirectly turning off glycolysis (in other words: don’t process pyruvate to acetyl-CoA because we already have a lot). The feedback system is known as the Randle cycle and appears (roughly) as the dotted line in our expanded metabolic scheme.

robin_map_2012-2Where we are going. In our earlier work Dr. Fine and I and our assistant, Anna Miller, found that if we grow cancer cells in culture, acetoacetate (one of the ketone bodies) will inhibit their growth and will reduce the amount of ATP that they can generate. Normal cells, however, are not inhibited by ketone bodies and the cells may even be using them. Our working explanation is that the ketone bodies are inhibiting the cancer cell through the Randle cycle. Now, normal cells can maintain energy, that is compensate for the Randle cycle, by running the TCA cycle (in fact, that is the purpose of the Randle cycle: to switch fuel sources). The cancer cells, however, have some kind of  defect in aerobic metabolism and can’t compensate.  How does this happen? That’s what we’re trying to find out but we have a good guess. (A good guess in science means that when we find out it’s wrong we’ll probably see a better idea). We find that our cancer cells in culture over-express a protein called uncoupling protein-2 (UCP2). We think that’s a player. To be discussed in Part IV.

American Diabetes Association Embraces Low-Carbohydrate Diets. Can You Believe It?

Posted: December 27, 2013 in American Diabetes Association, diabetes, glucose, saturated fat
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The  SBU (Swedish Council on Health Technology Assessment) is charged by the Swedish government with assessing health care treatments. Their recent acceptance of low-carbohydrate diets as best for weight loss is one of the signs of big changes in nutrition policy.  I am happy to reveal the next bombshell, this time from the American Diabetes Association (ADA) which will finally recognize the importance of reducing carbohydrate as the primary therapy in type 2 diabetes and as an adjunct in type 1.  Long holding to a very reactionary policy — while there were many disclaimers, the ADA has previously held 45 – 60 % carbohydrate as some kind of standard — the agency has been making slow progress. A member of the writing committee who wishes to remain anonymous has given me a copy of the 2014 nutritional guidelines due to be released next year, an excerpt from which, I reproduce below. (more…)

Revolutions. Political and Scientific

Posted: July 30, 2013 in Claude Bernard, gluconeogenesis, glucose, glycogen
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Paris. The summer of 1848. Mobs filled the streets, building barricades just like in Les Mis. If they’d had cars, they probably would have been set on fire.  In February of that year, the King, Louis-Phillipe, had abdicated in yet another French Revolution.  There was a new government, what is called the Second Republic, but whatever it tried to do, it didn’t make anybody happy and there was more unrest. At the Collège de France, faculty complained that it had “slackened the zeal for research among all of the chemists, and all of their time … is absorbed by politics.”

Horace_Vernet-Barricade_rue_Soufflot

 Figure 1. The Revolution of 1848. Barricades on the Rue Soufflot (Horace Vernet)

Bernard (more…)

Soda and the Nanny State

Posted: March 15, 2013 in Fructose, low-carbohydrate diet, Lustig, Occam's Razor, Uncategorized
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Mayor-Bloomberg-The-Littlest-Dictator--99309

My comments in answer to Jonny Bowden’s Huffington Post take on the sugar tax where he suggested that despite it’s flaws, “it’s all we’ve got.” I insisted that It’s not all we’ve got. We have the science and, in one afternoon, Bloomberg could convene a panel of scientists to evaluate presentations by all the players including me who believe that sugar is a smokescreen for not facing the importance of total carbohydrate restriction which you [Jonny Bowden], among others, have explained. Everybody should be heard. What I see is another rush to judgement like the low fat fiasco which we still have with us.

That you “have to do something” comes right out of Senator McGovern’s mouth as in Fat Head. And “deadly white substance that literally creates hormonal havoc and appetite dysregulation … promoting metabolic syndrome, diabetes, obesity and heart disease” is way outside of the bounds of science. I am not the only one to point out that Lustig’s population study represented the return of Ancel Keys.

We go with science or we don’t.

(more…)

Suddenly last summer. Part II

Posted: October 2, 2012 in Cancer, Cell Signaling, low-carbohydrate diet
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In the last post, I had proclaimed a victory for dietary carbohydrate restriction or, more precisely, recognition of its explicit connection with cell signaling. I had anointed the BMC Washington meeting as the historic site for this grand synthesis. It may have been a matter of perception — many researchers in carbohydrate restriction entered the field precisely because it came from the basic biochemistry where the idea was that the key player was the hormone insulin and glucose was the major stimulus for pancreatic secretion of insulin. We had largely ignored the hook-up with cell-biology because of the emphasis on calorie restriction, and it may have only needed getting everybody in the same room to see that the role of insulin in cancer was not separate from its role in carbohydrate restriction. (more…)

Reading the Scientific Literature. A Guide to Flawed Studies.

Posted: July 11, 2012 in Association and Causality, The Nutrition Story, triglycerides
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Doctor:    Therein the patient

  Must minister to himself.

Macbeth: Throw physic [medicine] to the dogs; I’ll none of it.

— William Shakespeare, Macbeth

The quality of nutrition papers even in the major scientific and medical journals is so variable and the lack of restraint in the popular media is so great that it is hard to see how the general public or even scientists can find out anything at all. Editors and reviewers are the traditional gate-keepers in science but in an area where rigid dogma has reached Galilean proportions, it is questionable that any meaningful judgement was made: it is easy to publish papers that conform to the party line (“Because of the deleterious effects of dietary fructose, we hypothesized that…”) and hard to publish others: when JAMA published George Bray’s “calorie-is-a-calorie” paper and I pointed out that the study more accurately supported the importance of carbohydrate as a controlling variable, the editor declined to publish my letter.  In this, the blogs have performed a valuable service in providing an alternative POV but if the unreliability is a problem in the scientific literature, that problem is multiplied in internet sources. In the end, the consumer may feel that they are pretty much out there on their own. I will try to help.  The following was posted on FatHead’s Facebook page:

 How does one know if a study is ‘flawed’? I see a lot of posts on here that say a lot of major studies are flawed. How? Why? What’s the difference if I am gullible and believe all the flawed studies, or if I (am hopefully not a sucker) believe what the Fat Heads are saying and not to believe the flawed studies — eat bacon.

Where are the true studies that are NOT flawed…. and how do I differentiate? : /

 My comment was that it was a great question and that it would be in the next post so I will try to give some of the principles that reviewers should adhere to.  Here’s a couple of guides to get started. More in future posts:

 1. “Healthy” (or “healthful”) is not a scientific term. If a study describes a diet as “healthy,” it is almost guaranteed to be a flawed study.  If we knew which diets were “healthy,” we wouldn’t have an obesity epidemic. A good example is the paper by Appel, et al. (2005). “Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial,” whose conclusion is:

“In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure, improve lipid levels, and reduce estimated cardiovascular risk.”

 It’s hard to know how healthful the original diet, a “carbohydrate-rich diet used in the DASH trials … currently advocated in several scientific reports” really is if removing carbohydrate improved everything.

Generally, understatement  is good.  One of the more famous is from Watson & Cricks’s 1953 paper in which they proposed the DNA double helix structure. They said “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”  A study with the word “healthy” is an infomercial.

2. Look for the pictures (figures).  Presentation in graphic form usually means the author wants to explain things to you, rather than snow you.  This is part of the Golden Rule of Statistics that I mentioned in my blogpost “The Seventh Egg”  which discusses a very flawed study from Harvard on egg consumption. The rule comes from the book PDQ Statistics:

“The important point…is that the onus is on the author to convey to the reader an accurate impression of what the data look like, using graphs or standard measures, before beginning the statistical shenanigans.  Any paper that doesn’t do this should be viewed from the outset with considerable suspicion.”

The Watson-Crick  paper cited above had the diagram of the double-helix  which essentially became the symbol of modern biology.  It was drawn by Odile, Francis’s wife, who is described as being famous for her nudes, only one of which I could find on the internet.

Krauss, et. al. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia.

The absence of a figure may indicate that the authors are not giving you a chance to actually see the results, that is, the experiment may not be flawed but the interpretation may be misleading, intentionally or otherwise.  An important illustration of the principle is a paper published by Krauss. It is worth looking at this paper in detail because the experimental work is very good and the paper directly — or almost directly — confronts a big question in diet studies: when you reduce calories by cutting out carbohydrate, is the effect due simply  to lowering calories or is there a specific effect of carbohydrate restriction.  The problem is important since many studies compare low-carbohydrate and low-fat diets where calories are reduced on both. Because the low-carbohydrate diet generally has the better weight loss and better improvement in HDL and triglycerides, it is said that it was the weight loss that caused the lipid improvements.

So Krauss compared the effects of carbohydrate restriction and weight loss on the collection of lipid markers known collectively as atherogenic dyslipidemia.  The markers of atherogenic dyslipidemia, which are assumed to predispose to cardiovascular disease, include high triglycerides (triacylglycerol), low HDL and high concentrations of the small dense LDL.

Here is how the experiment was set up: subjects first consumed a baseline diet of  54% of energy as carbohydrate, for 1 week. They were then assigned to one of four groups.  Either they continued the baseline diet, or they kept calories constant but reduced carbohydrate by putting fat in its place.  The three lower carbohydrate diets had 39 % or 26 % carbohydrate or 26 % carbohydrate with higher saturated fat.  After 3 weeks on constant calories but reduced carbohydrate, calories were decreased by 1000 kcal/d for 5 week and, finally, energy was stabilized for 4 weeks and the features of atherogenic dyslidemia were measured at week 13.  The protocol is shown in the figure from Krauss’s paper:

The Abstract of the paper describes the outcomes and the authors’ conclusions.

Results: The 26%-carbohydrate, low-saturated-fat diet reduced [atherogenic dylipidemia]. These changes were significantly different from those with the 54%-carbohydrate diet. After subsequent weight loss, the changes in all these variables were significantly greater…(my italics)

 Conclusions: Moderate carbohydrate restriction and weight loss provide equivalent but non-additive approaches to improving atherogenic dyslipidemia. Moreover, beneficial lipid changes resulting from a reduced carbohydrate intake were not significant after weight loss.

Now there is something odd about this.  It is the last line of the conclusion that is really weird. If you lose weight, the effect of carbohydrate is not significant?  As described below, Jeff Volek and I re-analyzed this paper so I have read that line a dozen times and I have no idea what it means.  In fact, the whole abstract is strange.  It will turn out that the lower (26 %) is certainly “significantly different from.. the 54%-carbohydrate diet” but it is not just different but much better. Why would you not say that?  The Abstract is generally written so that it sounds negative about low carbohydrate effects but it is already known from Krauss’s previous work and others that carbohydrate restriction has a beneficial effect on lipids and the improvements in lipid markers occur on low-carbohydrate diets whether weight is lost or not.  The last sentence doesn’t seem to make any sense at all.    For one thing, the experiment wasn’t done that way.  As set up, weight loss came after carbohydrate restriction.  So, let’s look at the data in the paper.  There are few figures in the paper and Table 2 in the paper presents the results in a totally mind-numbing layout.  Confronted with data like this, I sometimes stop reading.  After all, if the author doesn’t want to conform to the Golden Rule of Statistics, if they don’t want to really explain what they accomplished, how much impact is the paper going to have.  In this case, however, it is clear that the experiment was designed correctly and it just seems impossible from previous work that this wouldn’t support the benefits of carbohydrate restriction and the negative tone of the Abstract needs to be explained.  So we all had to slog through those tables.  Let’s just look at the triglycerides since this is one of the more telling attributes of atherogenic dyslpidemia.  Here’s the section from the Table:

Well this looks odd in that the biggest change is in the lowest carb group with high SF but it’s hard to tell what the data look like.  First it is reported as logarithms. You sometime take logs of your data in order to do a statistical determination but that doesn’t change the data and it is better to report the actual value.  In any case, it’s easy enough to take antilogs and we can plot the data.  This is what it looks like:

It’s not hard to see what the data really show: Reducing carbohydrate has an overwhelming effect on triglycerides even without weight loss.  When weight loss is introduced, the high carbohydrate diets still can’t equal the performance of the carbohydrate reduction phase.  (The dotted line in the figure are data from Volek’s earlier work which Krauss forgot to cite).

The statements in the Conclusion from the Abstract are false and totally misrepresent the data.  It is not true as it says “carbohydrate restriction and weight loss provide equivalent…” effects. The carbohydrate-reduction phase is dramatically better than the calorie restriction phase and it is not true that they are “non-additive”  Is this an oversight?  Poor writing?  Well, nobody knows what Krauss’s motivations were but Volek and I plotted all of the data from Krauss’s paper and we published a paper in Nutrition & Metabolism providing an interpretation of Krauss’s work (with pictures).  Our conclusion:

Summary Although some effort is required to disentangle the data and interpretation, the recent publication from Krauss et al. should be recognized as a breakthrough. Their findings… make it clear that the salutary effects of CR on dyslipidemia do not require weight loss, a benefit that is not a feature of strategies based on fat reduction. As such, Krauss et al.  provides one of the strongest arguments to date for CR as a fundamental approach to diet, especially for treating atherogenic dyslipidemia.

An important question in this experiment, however, is whether even in the calorie reduction phase, calories are actually the important variable.  This is a general problem in calorie restriction studies if for no other reason than that there is no identified calorie receptor.  When we published this data, Mike Eades pointed out that in the phase in which Krauss reduced calories, it was done by reducing macronutrients across the board so carbohydrate was also reduced and that might be the actual controlling variable so we plotted the TAG against carbohydrate in each phase (low, medium and high carb (LC, MC, HC) without or with weight loss (+WL) and the results are shown below

This is remarkably good agreement for a nutrition study. When you consider carbohydrates as the independent variable, you can see what’s going on.  Or can you?  After all, by changing the variables you have only made an association between carbohydrate and outcome  of an experiment. So does this imply a causal relation between carbohydrate and triglycerides or not?  It is widely said that observational studies do not imply causality, that observational studies can only provide hypothesis for future testing. It certainly seems like causality is implied here.  It will turn out that a more accurate description is that observational studies do not necessarily imply causality and I will discuss that in the next posts.  The bottom line will be that there is flaw in grand principles like “Random controlled trials are the gold standard.” “Observational studies are only good for generating hypotheses,”  “Metabolic Ward Studies are the gold standard.” Science doesn’t run on such arbitrary rules.

Introduction to Metabolism. The Black Box of Life.

Posted: February 2, 2012 in energy metabolism, glycolysis, Krebs cycle, low-carbohydrate diet
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I am currently teaching nutrition and metabolism to first year medical students.  The problem in this subject is the large number of individual reactions which leads students to think of the subject the way somebody described the study of history: just one damned thing after another.  I try to present the big picture and the approach is the systems or “black box”  strategy.  The method is to ask whether we can get some information just by looking at the inputs and outputs to a system even if we don’t know any of the details of what’s going on inside.  In other words, it is a way of organizing limited information.  The method is favored by engineers who are the people most unhappy with the idea that they don’t know anything at all.  First, the big principles.

Metabolism: two goals, two fuels.  

There are two major goals in human energy metabolism: First, to provide energy for life processes in the form of the molecule ATP and second, to provide glucose for those cells that require glucose (particularly brain and central nervous system) and to maintain blood glucose at a relatively constant level: too little is obviously not good but too much is also a problem in that glucose is chemically reactive and can interact with body material, particularly proteins when at high concentrations. Of course, metabolism does many things but these are the two major goals in providing energy.

A second big generalization is that in this process there two kinds of fuels: glucose and acetyl-Coenzyme A (abbreviated acetyl-CoA or sometimes written as acetyl-SCoA; the S, which is meant to show that the compound contains sulfur, is not pronounced).

The black box of life. 

You knew what we do in metabolism even before you started reading this. Putting it into black box terms, you knew: we take in food and we take in oxygen. We excrete CO2 and water.  Somehow this gives us the energy for life as well as the material to build up components of the body.  You don’t have to know too much chemistry to figure out the important conclusion that, inside the black box, living systems use oxidation, just like combustion in a furnace. Lavoisier’s whole animal calorimeter that I described in a previous post was a beautiful real demonstration of this black box.  More technically, this is an oxidation-reduction reaction.  Oxidation, in a biochemical context, means combination with oxygen or loss of hydrogen and reduction means loss of oxygen or gain of hydrogen; we say that the (carbons in the) food gets oxidized and the oxygen gets reduced (to water).  Like the common oxidation reactions you know (combustion in a furnace or an automobile engine), this produces energy which can be used to do work. Some work is mechanical work — moving muscles — but most of the energy is used for chemical: work making body material and keeping biological structures intact and generally keeping things running.  The medium of energy in metabolism is the chemical reaction of synthesis and breakdown of the molecule ATP.  Textbooks frequently refer to ATP as a “high energy molecule” but it is not the compound itself but rather the reaction (synthesis and breakdown (hydrolysis)) that is high energy.  For the moment, we can think of ATP as the “coin of energy exchange in metabolism.”  A heavy-duty thought concept: the challenge for biochemistry historically was to explain how the energy from an oxidation-reduction reaction could be used to carry out the synthesis of ATP which has a different mechanism (phosphate transfer).  The process is called oxidative phosphorylation and was only figured out about fifty years ago.

So again, our two goals in human metabolism: Make energy in the form of ATP and maintain a pretty much constant level of blood glucose for those cells, brain and central nervous system, that require glucose (the brain can’t use fatty acids as a fuel).

Let’s look at energy production first because it is a little easier to understand.  As we look inside the black box, each of the processes uncovered will have its own degree of complexity.  In reading this you have to do what scientists do: hang in there.  Skip over the parts that seem complex and see if you can come back to them later.

The role of redox coenzymes

So, breaking into the black box, the first thing to notice is that the oxidation of food is done in steps, and that there is another player that mediates the process by coupling separate pieces: the food never sees the oxygen.  The intermediaries are called coenzymes or cofactors.  The most important oxidative coenzyme is known as NAD.  It’s always referred to by the acronym, but if you’ve had some organic chemistry and you’re curious, NAD stands for nicotinamide-adenine-dinucleotide; the structure is shown in the figure and the action end of the molecule is indicated. NAD coenzymes are derived from the vitamin niacin.  So   what happens in metabolism is that food is oxidized by NAD+ (the oxidized form of NAD) and the product, NADH (the reduced form) is re-oxidized by molecular oxygen. Although it is still just as we thought (food+oxygen-in, CO2+water-out), the oxygen never sees the food.   Why do we do it this way?  If we did it all in one big blast like an automobile engine, we would have little control over it and we would not be able to capture the energy in a usable chemical form.

It’s easiest to start with glucose, a six-carbon compound. The early steps in metabolism involve a process known as glycolysis (sugar splitting) that ultimately gives you two molecules of a three-carbon compounds known as pyruvic acid. Pyruvic acid is oxidized to a derivative of acetic acid, known as acetyl-CoA. The CoA is short for Coenzyme A, a complicated molecule but, like many coenzymes is always referred to in this way so it is not important to know the detailed structure.  The compound is frequently written acetyl-SCoA to emphasize that it is a thioester (sulfur ester); again, the “S” is not pronounced.

Acetyl-SCoA is the fuel for the major NADH-producing process, known as the Krebs cycle after the major player in its discovery. Without looking into that black box too much the key compound is citric acid, which is, chemically a try-carboxylic acid (TCA) so the Krebs cycle is also called the citric acid cycle or TCA cycle; Krebs called it the TCA cycle so I will generally use that term.  The process whereby NADH is finally re-oxidized by oxygen is known as electron transport.  So, The big black boxes of metabolism:

Where do we get Glucose and Acetyl-CoA?

So far we know: most energy comes from the oxidation of acetyl-CoA and most of the glucose that provides energy does so by first being converted to acetyl-CoA. Where else can we get acetyl-CoA? We’ve taken glucose as synonymous with food but where else can we get glucose from besides the diet?

Looking ahead, the big results that will come out of opening up the black box of metabolism: 1) Acetyl-CoA also comes from fat and to a smaller extent from protein.  2) Glucose can also be formed from protein. 3) Under conditions where there is no dietary glucose (starvation, low carbohydrate diet), glucose will be made from protein or released from stored glycogen, and an alternative fuel ketone bodies will provide acetyl-CoA; ketone bodies are essentially a dimer of acetyl-CoAs and the liver makes and exports ketone bodies to other cells.  Acetyl-CoA and, therefore, glucose can be converted to fat but a major asymmetry that will have profound significance is that 4) glucose cannot be formed from acetyl-CoA.  The significance of the last statement is that: we know all too well that fat can be formed from glucose but, with minor exceptions, 5) glucose cannot be formed from fat. (Chris Masterjohn’s post “We Really Can Make Glucose From Fatty Acids After All!”
indicates the extent to which the exceptions become important but the overriding principle that has the most impact on metabolism is that you cannot make glucose from fat).
So that’s it.  You now have a blackbox view of metabolism.  I will try to open some of the boxes in future posts.

Summary of fuel sources and synthesis and looking ahead.

  1. There are, roughly speaking, two kinds of fuels: glucose and acetyl-CoA.
  2. Carbohydrates and other nutrients, fat (that is, fatty acids) and protein (amino acids) can supply acetyl-CoA.  Glucose is not required for acetyl-CoA and under conditions of low carbohydrate or low total food, fatty acids become the major source of acetyl-CoA.
  3. Not all tissues can use all fuel sources. Brain, CNS and red blood cells, for example cannot use fatty acids. Brain and CNS can use acetyl-CoA but cannot get it from fatty acids.  Red blood cells only use glucose and, to a first approximation, brain and CNS are also dependent on glucose for metabolism.
  4. Under conditions of starvation or carbohydrate restriction, acetyl-CoA can be effectively transported from the liver in the form of  ketone bodies. Ketone bodies, then, are a source of acetyl-CoA that can be used by brain and CNS.  Red blood cells are still dependent on glucose but the brain’s demand for glucose is reduced by the availability of ketone bodies.
  5. There is no dietary requirement for carbohydrate and amino acids can also supply glucose through the process of gluconeogenesis.
  6. Fat as a source of acetyl-CoA also works the other way: acetyl-CoA can be converted to fat.
  7. Whereas glucose can be converted to fat, with a few exceptions, fat cannot be converted to glucose. This will be a key idea behind carbohydrate restriction.
  8. Glucose can also be stored as the polymer glycogen.
  9. Bottom line is the limitation of “you are what you eat.” Metabolism means the interconversion of food and metabolites. Conversely, it will be critical that not everything is interconvertible. In particular, we will emphasize that you can make fat from carbohydrate but, to a large extent,  you cannot make glucose from fat.

Looking ahead on sources of blood glucose:

  1. Glucose from dietary input (referred to as the fed state; in nutrition, as the postprandial period), is depleted after about 8 hours.
  2. Glycogen is a storage/supply source of glucose.  Liver glycogen can supply export glucose to the blood, thereby supplying other tissues.  Muscle glycogen supplies glucose only for the muscle itself.  Glycogen may become largely depleted after 24 hours, depending on the conditions (exercise, for example).
  3. The third source of blood glucose is gluconeogenesis (GNG) which, as the name implies, makes glucose anew from existing metabolites. Depending on the conditions, the source of carbon may be amino acids, lactic acid or glycerol from fat metabolism.  Whereas it is sometimes indicated to be a “last ditch” source of glucose in the textbooks, it goes on all the time. The glucose it synthesizes in GNG may be used to replenish glycogen and only appear in the blood at a later time.

Slouching toward Low-Carb. “We Thought of This First.”

Posted: January 3, 2012 in American Diabetes Association, low-carbohydrate diet, Research Integrity, The Nutrition Story
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The joke in academic circles is that there are three responses to a new idea. First, “This is wrong,” second, “There’s nothing new in this,” and third, the sub-title of this post. Priority in a scientific discovery is fundamental in science, however, and “we thought of this first” is not always that funny.  Getting “scooped” can have serous practical consequences like jeopardizing your grant renewal and, if nothing else, most of us are motivated by a desire to solve the problem and don’t like the feeling that, by analogy, somebody came along and filled in our crossword puzzle.  In dietary carbohydrate, all three of the responses co-exist.  While an army of dietitians is still claiming that people with diabetes need ever more carbohydrate, in the background the low-fat paradigm crumbles and, somewhat along the lines of the predictions in A Future History of Diabetes , the old guard are coming forward to tell us that they have been recommending low-carb all along.

The latest discoverer of the need to reduce dietary carbohydrate is David Jenkins whose recent paper is entitled “Nuts as a Replacement for Carbohydrates in the Diabetic Diet.” [1] The title is crazy enough, following the tradition of getting away from nutrients, that is, well-defined variables, and replacing it with “food,” that is, mixtures of everything. It is, in fact, not really a low carbohydrate study but the experimental design is not the problem.  It is the background and rationale for the study which recognizes the disintegration of the low-fat diet paradigm but, at the same time, fails to cite any of the low-carbohydrate studies that have been instrumental in showing the need to replace carbohydrates in the diabetic diet. Given forty years of studies showing the benefits of low carbohydrate diets and forty years of unrestrained attacks on the method, it will be interesting to see how Jenkins shows that it is actually the nutritional establishment that invented carbohydrate restriction.

Disputes over priority are well known in the history of science. Newton’s frequently quoted statement that he had seen farther than others because he had “stood on the shoulders of giants” has been interpreted by some historians as a sarcastic comment aimed at Robert Hooke  with whom he had, among other things, a dispute over the priority for the inverse square law (force of gravity varies as the inverse of the square of the distance: F = GmM/g2). Hooke was short and suffered from kyphosis and is assumed not to have shoulders you would profitably stand on.

Even Einstein had trouble.  His dispute with the mathematician David Hilbert about priority for the field equations of general relativity (also about gravity) is still going on, a dispute that I prefer to stay out of. Cited by his biographer, Abraham Pais, Einstein had apparently made up the  verb to nostracize (nostrazieren) which he accused Hilbert of doing. (He meant that Hilbert had made Einstein’s idea community knowledge.  Googling the word gives you only “ostracize” and “Cosa Nostra.”)

It is not the priority dispute, per se — the original low carbohydrate diet is usually attributed to William Banting who published the Letter on Corpulence in 1863, although Brillat-Savarin’s 1825 Physiologie du goût  understood the principle. He said that some people were carbophores and admitted to being one himself.  It is not just priority but that the people who are now embracing carbohydrate restriction were previously unrestrained in their attacks on the dietary approach and were adamant in denying the strategy to their patients.

David Jenkins: “Nuts.”

In trying to find an appropriate answer to the recent bit of balderdash by the redoubtable Hope Warshaw, Tom Naughton recounted the story of the Battle of the Bulge of WWII.  Towards the end of the war, Hitler launched a massive winter attack around the city of Bastogne where, at one point, American Forces were surrounded. When the Germans demanded surrender, the American General, Anthony McAuliffe, sent the one-word reply: “Nuts!”  I always thought it was a euphemism and that he actually went “Vice-presidential” as it was called in the last administration, but it turns to have been a common expression with him and he really did write “nuts” which, of course, had to be explained to the German couriers. (There is a “Nuts” Museum in Bastogne commemorating the battle which the Americans won somewhat as described in the movie Patton).

For installation in the Nutritional Nuts Museum and as an example of the current attempts to co-opt carbohydrate restriction, one can hardly beat Jenkins’s recent paper [1].

Richard:…Who knows not that the gentle duke is dead? ….

King Edward: Who knows not he is dead! Who knows he is?

Queen Elizabeth: All-seeing heaven, what a world is this!

— William Shakespeare, Richard III

The trick is to act as if the point you are making is already established. The Abstract of Jenkins study: “Fat intake, especially monounsaturated fatty acid (MUFA), has been liberalized in diabetic diets to preserve HDL cholesterol and improve glycemic control….” It has? Liberalized by whom?  Although the American Diabetes Association guidelines are traditionally all over the place, few would consider that there is any sense of substantial liberalization on replacing carbohydrate with fat from them or any health agency.

“Replacement of carbohydrate by healthy fat … has been increasingly recognized as a possible therapeutic strategy in the treatment of diabetes [2] as concerns emerge over the impact of refined carbohydrate foods in increasing postprandial glycemia and reducing HDL cholesterol.”  Reference [2] ((1) in the original) actually “emerged” in 2002 and is ambiguous at best: “Carbohydrate and monounsaturated fat together should provide 60–70% of energy intake.” (It is not my style of humor, but the behavioral therapists call this “shoulding on people.”) The paper admits that the evidence “is based on expert consensus”  and contains what might be called the theme song of the American Diabetes Association:

 “Sucrose and sucrose-containing food do not need to be restricted by people with diabetes based on a concern about aggravating hyperglycemia. However, if sucrose is included in the food/meal plan, it should be substituted for other carbohydrate sources or, if added, be adequately covered with insulin or other glucose-lowering medication.” (my italics)

In fact, one emerging piece of evidence is Jenkins 2008 study comparing a diet high in cereal with a low glycemic index diet [3].  The glycemic index is a measure of the actual effect of dietary glucose on blood glucose.  Pioneered by Jenkins and coworkers, a low-GI diet is based on the same rationale as a low-carbohydrate diet, that glycemic and insulin fluctuations pose a metabolic risk but it emphasizes “the type of carbohydrate,” that is, it is a politically correct form of low-carbohydrate diet and as stated in the 2008 study: “We selected a high–cereal fiber diet treatment for its suggested health benefits for the comparison so that the potential value of carbohydrate foods could be emphasized equally for both high–cereal fiber and low–glycemic index interventions.” (my emphasis) The Conclusion of the 24-week study was: “In patients with type 2 diabetes, 6-month treatment with a low–glycemic index diet resulted in moderately lower HbA1c levels compared with a high–cereal fiber diet.”  The figure below shows the results for HbA1c and weight loss and just looking at the figures, the results are certainly modest enough.

By coincidence, on almost the same day, Eric Westman’s group published a study that compared a low glycemic index diet with a true low carbohydrate diet [4].  The studies were comparable in duration and number of subjects and a direct comparison shows the potential of low carbohydrate diets (NOTE: in the figure, the units for the change are those of the individual parameters; an earlier version showed this as % which was an error):

 

Fad_Westman_Jenkins_FigWe thought of this first.

Oddly, neither of these papers are cited in the current study by Jenkins, et al.  In fact, according to the paper, the precedents go way back:

“Recently, there has been renewed interest in reducing carbohydrate content in the diet of diabetic patients. In 1994, on the basis of emerging evidence, the American Diabetes Association first suggested the possibility of exchanging dietary carbohydrate for MUFA in dietary recommendations for type 2 diabetes). Although not all studies have shown beneficial effects of MUFAs in diabetes, general interest has persisted, especially in the context of the Mediterranean diet.”

The ADA discovered low carbohydrate diets ? Did my blogpost see it coming, or what? But wait…

 “low carbohydrate intakes have also been achieved on the Atkins diet by increasing animal fats and proteins. This influential dietary pattern is reflectedin the relatively lower pre-study carbohydrate intakes of ~ 45% in the current study rather than the 50–60% once recommended.

The researchers in this area might not feel that 45 % carbohydrate has much to do with the Atkins diet but, in any case, it appears not to have been “influential” enough to actually get the studies supporting it cited.

Again: “Fat intake, especially monounsaturated fatty acid (MUFA), has been liberalized…” but “… the exact sources have not been clearly defined. Therefore, we assessed the effect of mixed nut consumption as a source of vegetable fat on serum lipids and HbA1c in type 2 diabetes.”  Therefore? Nuts?  That’s going to clearly define the type of MUFA?  Nuts have all kinds of nutrients.  How do we know that it is the MUFA in the nuts?  In fact, the real question is whether any benefit would not be due to the reduction in carbohydrate regardless of what it were replaced with. So what was the benefit? The figure above shows the effect on hemoglobin A1C. As described by the authors:

 “The full-nut dose reduced HbA1c by two-thirds of the reduction recognized as clinically meaningful by the U.S. Food and Drug Administration (.0.3% absolute HbA1c units) in the development of antihyperglycemic drugs…”

 In other words, almost meaningful, and

 “the number of participants who achieved an HbA1c concentration of <7% (19 pre-study participants, down to 13 post-study participants) was significantly greater on the nut treatment than on the muffin treatment (20 pre-study participants, remaining at 20 post-study participants…).”

This is some kind of accomplishment but the figure above shows that, in fact, the results were pretty poor.  The statistics do show that the “full nut dose” was significantly different from the half-nut dose or the muffin.  But is this what you want to know?  After all, nobody has an average change in HbA1c.  What most of us want to know is the betting odds. If I down all those nuts, what’s the chance that I’ll get better.  How many of the people in the full-nut study did better than those in the half-nut study (did the authors not know that this would sound funny?).  You can’t tell for sure because this information is buried in the statistics but the overlap of the error bars, highlighted in pink, suggests that not everybody gained anything — in fact, some may have gotten worse.

What kind of benefit is possible in a dietary intervention for people with diabetes?  Well, the studies discussed above from Jenkins himself and from Westman show that, with a low-GI diet, it is possible to obtain an average reduction of about 4 %, more than ten times greater than with nuts and with a real low-carbohydrate diet much greater.  I have added an inset to the Figure from Jenkins with data from a 2005 study by Yancy, et al. [5].  The red line shows the progress of the mean in Yancy’s studied.  If you had diabetes, would you opt for this approach or go for the full-nut dose?

Bibliography

1. Jenkins DJ, Kendall CW, Banach MS, Srichaikul K, Vidgen E, Mitchell S, Parker T, Nishi S, Bashyam B, de Souza R et al: Nuts as a replacement for carbohydrates in the diabetic diet. Diabetes Care 2011, 34(8):1706-1711.

2. Franz MJ, Bantle JP, Beebe CA, Brunzell JD, Chiasson JL, Garg A, Holzmeister LA, Hoogwerf B, Mayer-Davis E, Mooradian AD et al: Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care 2002, 25(1):148-198.

3. Jenkins DJ, Kendall CW, McKeown-Eyssen G, Josse RG, Silverberg J, Booth GL, Vidgen E, Josse AR, Nguyen TH, Corrigan S et al: Effect of a low-glycemic index or a high-cereal fiber diet on type 2 diabetes: a randomized trial. JAMA 2008, 300(23):2742-2753.

4. Westman EC, Yancy WS, Mavropoulos JC, Marquart M, McDuffie JR: The Effect of a Low-Carbohydrate, Ketogenic Diet Versus a Low-Glycemic Index Diet on Glycemic Control in Type 2 Diabetes Mellitus. Nutr Metab (Lond) 2008, 5(36).

5. Yancy WS, Jr., Foy M, Chalecki AM, Vernon MC, Westman EC: A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutr Metab (Lond) 2005, 2:34.

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.

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