Archive for the ‘Volek-Westman principle’ Category

Confronting the Crisis in Nutrition. The Office of Research Integrity Conference on Quest for Research Excellence.

Posted: March 12, 2012 in Crisis in Nutrition, low-carbohydrate diet, Research Integrity, The Nutrition Story, Volek-Westman principle
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The Office of Research Integrity is hosting a conference on the Quest for Research Excellence and, for the first time, there is session that directly confronts policy and The Crises in Nutrition. The Speakers will delineate the problem — the two worlds of establishment nutrition and the major challenge of low carbohydrate diets, the growing problems of childhood obesity and our failure to deal with it, the confusion in the popular press on scientific issues, and finally, the voice of the patient, the failure to listen to the people who are dissatisfied with official guidelines and who have found workable solutions themselves. Three specific goals are recommended: 1) open hearings in which all researchers are represented, 2) funding research in which all people in low carbohydrate research work with others and finally, 3) a new oversight agency from NSF or Office of Research and Technology Policy.

The three goals may be a useful crystallizing point for moving forward. What can you do?

  1. Contact your elected officials and copy one of the authors from the conference. Use the Abstracts below as a basis for your own version of what needs to be done. The three goals can be more narrowly focussed for your own interests.
  2. Encourage local media to cover the meeting. Information is at http://ori.hhs.gov and the speakers can be contacted directly.
  3. Publicize your version of the three goals on your blog, your facebook page or other social media.

2011 Office of Research Integrity Conference Washington DC

Quest for Research Excellence, March 15, 2012.

Session on Crisis in Nutrition.

Chair: Richard David Feinman Contact Information: feinman@mac.com (917) 554-7794

Introduction and Abstracts.

The interest in nutrition for general health and for the prevention and treatment of disease is probably greater than at any time in history. A fairly large research community has grown up to provide information on the subject but the excellence of the results and their ability to inform the general public is highly questionable. The prospect for the future quality of research is similarly discouraging. This session focusses on a crisis in nutrition: the confusion in the public’s mind and the lack of accountability of official agencies and their failure to consider minority points of view. Four areas are considered in this session: the need to consider work that has been done on carbohydrate restriction (the major alternative to current recommendations), the limitations of current media representations of research, the problem of childhood obesity, and finally, the failure to listen to the patients who have not been well served by current ideas and who have discovered alternatives for themselves. The public, athrough forums and comments to blogs and other social media, have expressed substantial dissatisfaction with the current state of medical nutrition.

Three approaches are suggested as first steps for resolving the current crises:

  1. First, we need hearings to be held by congress or HHS in which all major researchers in nutrition are represented. We have to have everybody in the game. The USDA guidelines committee, the American Health Association nutrition panels have to meet with their critics. In particular, researchers in dietary carbohydrate restriction should be able to meet and discuss issues with their critics. This is what the government can do. Better than taxation or other punitive measures, they can bring out the information. The NIH or congress should hold meaningful hearings where all sides are heard.
  1. Second, we need to fund a study in which researchers in dietary carbohydrate restriction and critics of such diets cooperate to design a long-term comparison of CRD and low-fat diets, Mediterranean diets or whatever. The groups agree on methods of procedure, make-up of the diets, how compliance will be effected, and what parameters will be measured. They “write the paper first, leaving room for the data,” that is, they agree in advance on what the possible outcomes are and what conclusions could be drawn from them. In this way, the public and other scientists will have a sense that the issues have adequately been addressed and the results reliably evaluated.
  1. Finally, what’s needed is the creation of a new oversight organization, possibly under the auspices of the National Science Foundation or the Office of Science and Technology Policy in which scientists with no personal stake in nutrition, assess bias in grant awards and publications. The scientific principles involved in nutrition are neither so technical nor so profound that accomplished scientists from other fields cannot evaluate them. Such organizations might make recommendations (or indicate the limitations in existing knowledge that prevent making recommendations) after hearing all credentialed experts.

In the end, we have to say whether there is really a problem or not. Is their really an epidemic of obesity and overweight? Is there a crisis in the incidence of diabetes, or not? Are our health problems, the rising cost, the patient suffering, real? If they’re real, we have to use everything we have. We have to have real science and we can’t continue with one expert committee after another making recommendations but taking no responsibility for outcomes and refusing to show any willingness to confront their critics.

Crisis in nutrition: I. Research Integrity and the Challenge of Carbohydrate Restriction.

Author: Richard David Feinman.

Objective: Research integrity extends beyond falsification of data and explicit misconduct. We assessed the extent to which established majority opinion recommending dietary fat and saturated fat reduction has failed to cite contradictory evidence, accepted undocumented conclusions and marginalized contributions of alternative points of view, specifically the role of dietary carbohydrate restriction, the major challenge to current recommendations..

Main points: Government and private health agencies have long recommended a reduction in dietary fat, particularly saturated fat, in the treatment or prevention of cardiovascular disease, obesity and diabetes. While there are many disclaimers, low-fat in some form remains the standard nutritional recommendation. Alternative strategies based on control of insulin fluctuations via carbohydrate restriction, while widely used by many in the community, have been discouraged if not actually attacked. This has contributed to a “two worlds” system that has increased confusion among scientists and the public. While there are many exceptions and some emerging acceptance of carbohydrate restriction — which frequently fails to cite earlier work — there is a perception of a majority opinion with pervasive control of the scientific infrastructure: editorial boards, study sections and health agency administration. Examples will be given of undocumented negative statements about low-carbohydrate diets, misrepresentation of data and extensive failure to cite relevant papers from the literature. Most troubling is the tendency to accept some of the conclusions previously demonstrated in low-carbohydrate research without, again, giving appropriate citations to that research. This has led a significant part of the population to distrust official recommendations and medical science.

There is a need to re-evaluate published data on carbohydrate restriction and to guarantee adequate peer review of future manuscripts and grant applications on macronutrient composition of the diet. More generally, better communication and cooperation between researchers and physicians with different opinions can only benefit science and society, a society that is admittedly not making good progress on obesity, diabetes and metabolic syndrome.

Conclusions & Recommendations:

Recommendations for better integration of different points of view include government-sponsored meetings where all scientific approaches can present their own opinions and address critics, representation on study sections and editorial boards of people with experience in carbohydrate restriction-insulin control diets and long term comparative trials that include PIs with experience and understanding of the role of the glucose-insulin axis in obesity, diabetes and metabolic syndrome. Agreement in advance between the “two worlds” as to the expected outcomes and interpretations would provide most benefit for the public and scientist-community interactions. Given the pervasiveness of the problem, in the end, intervention of new oversight agencies, e.g. from NSF or Office of Science and Technology, may be needed

Figure 1. Comparison of low-carbohydrate diets to low-GI diets and high cereal diets.

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

Author: Richard David Feinman.

Objective: The public relies on popular media for description of nutrition research. A major interest is the controversy over macronutrient composition of the diet and particularly the role carbohydrate-restriction, the major challenge to official recommendations. The goal is to assess the extent to which statements to the media and especially press releases from authors, author institutions and journals accurately represent the results of reported research. To determine the extent to which personal bias influences and is taken as fact by the media.

Main points: Authors of research papers should sensibly have great freedom in describing the implications of their research to the media, but it is important that the public be aware of when that opinion does or does not follow directly from the publication. Two examples are given. In one, an animal study (Foo, et al. Proc Natl Acad Sci USA 2009, 106: 15418-15423), the accompanying press release implied that it was motivated by observations of patients in a hospital which were not described, were unsubstantiated and would have been purely anecdotal. In a second example, a press release stated that carbohydrate-restricted diets (CRDs) were not included in a comparative study because of their low compliance (Sacks, et al. N Engl J Med 2009, 360: 859-873. No data were given to support this assertion and it is, in fact not true — CRDs have, on average, better compliance than other dietary interventions. The study concluded that the macronutrient composition of the diet was not important even though, as implemented, dietary intake was the same for the groups studied and, again, the CRD was not included in the study. It seems likely that that this would have an inhibiting effect on the willingness of individuals to choose a CRD, an outcome that was not justified by the published research.

Conclusions & recommendations: Practices should be evaluated and guidelines should be generated by academic societies, scientific journals and the popular media as to what constitutes appropriate press description of published research. Reasonable principle are that only those specific conclusions that derive directly from the publication. The generally accepted idea that authors make clear what is their personal opinion and what is the product of research should be the norm.

Biography: Richard David Feinman, PhD in Chemistry (University of Oregon) is Professor of Cell Biology at SUNY Downstate Medical Center. His current area of research is nutritional biochemistry and biochemical education especially as it relates to macronutrients and bioenergetics. He is founder of the Nutrition & Metabolism Society and former co-editor-in-chief of the journal Nutrition & Metabolism.

Figure 2. The world according to Reuters. Low-fat is good. It’s bad. It’s not as bad as we thought. Wait! Eat more fruits and vegetables. “The low-dat diet craze?” Is that what it’s been? Is?

Crisis in nutrition: III. Childhood Obesity: Prevention and Intervention  

Author: Wendy Knapp Pogozelski, Dept of Chemistry, SUNY Geneseo, Geneseo, NY 14454.

Objective: Almost one-third of American children aged 2-11 qualify as obese or overweight, with obesity-related diseases such as type 2 diabetes greatly on the rise in this population. Despite the labeling of the crisis as “epidemic,” funding to study childhood obesity has been limited and restricted to the traditional intervention strategies (to reduce calories, to reduce dietary fat and to exercise more) despite the fact that these efforts have been largely unsuccessful. The time has come for frank assessment of foundational beliefs about a) the causes of obesity in children and b) effective prevention and intervention strategies. This talk will discuss assumptions that are barriers to research and will compare results from traditional calorie-restriction programs with results from programs that have emphasized carbohydrate control and insulin reduction.

Main points: The current generation of children is predicted to be the first to experience a lower life expectancy than that of its parents. Children across the world are experiencing unparalleled rates of obesity, heart disease and type 2 diabetes. Relatively little formal research has addressed the causes of childhood obesity, perhaps due to an assumption that the problem is already understood. Despite reluctance to use children as subjects in studies that depart from the traditional “eat less and exercise more” philosophies, it has been noted that the current efforts, dietary recommendations, educational programs and mandates of school lunch programs could be characterized as experiments. These experiments, like the numerous interventions based on traditional strategies, have had poor results but it has been very difficult to implement or fund those approaches that focus on carbohydrate control despite demonstrable success in this area. We will examine typical meals given in schools and at home, compare data from various obesity interventions and discuss causes of obesity on a molecular level

Conclusions & recommendations: The crisis warrants policy change. 1) Funding for childhood obesity should be increased. 2) A broader range of methods and principal investigators should be instituted, with greater accountability required of funded investigators. 3) The USDA nutritional recommendations, a “one size fits all” guide for school meal programs should be reevaluated and reformulated to take into account all strategies for obesity prevention and intervention. 4) Education for physicians, dietitians and health care professionals, as well as the general public, should be altered to include an understanding of the most positive results in obesity prevention.

Biography: Wendy Pogozelski, PhD in Chemistry (Johns Hopkins University) is Professor of Chemistry at SUNY Geneseo. Her research has been in radiation effects, DNA damage, and DNA computing. Current efforts are directed toward biochemical-based nutrition education for health professionals, educators and the general public. In addition to developing teaching materials that incorporate nutrition research, Dr. Pogozelski writes and lectures on diabetes and works with local and national organizations to improve nutrition education.

Figure 3. Before and After from James Bailes’s No More Fat Kids

Crisis in nutrition: IV. Vox Populi

Authors: Tom Naughton, Jimmy Moore, Laura Dolson

Objective: Blogs and other social media provide insights into how the public views the current state of nutrition science and the official dietary recommendations. We ask what can be learned from online discussions among people who dispute and distrust the official recommendations.

Main points: A growing share of the population no longer trusts the dietary advice offered by private and government health agencies. They believe the supposed benefits of the low-fat, grain-based diets promoted by those agencies are not based on solid science and that benefits of low-carbohydrate diets have been deliberately squelched. The following is typical of comments the authors (whose websites draw a combined 1.5 million visitors monthly) receive daily:

“The medical and pharmaceutical companies have no interest in us becoming healthy through nutrition. It is in their financial interest to keep us where we are so they can sell us medications.”

Similar distrust of the government’s dietary recommendations has been expressed by doctors and academics. The following comments, left by a physician on one of the authors’ blogs, are not unusual:

“You and Denise Minger should collaborate on a book about the shoddy analysis put out by hacks like the Dietary Guidelines Advisory Committee.”

“Sometimes I wonder if people making these statements even took a basic course in biochemistry and physiology.”

Many patients have given up on their health care professionals and turn to Internet sites for advice they trust. This is particularly true of people with diabetes who find that a low-fat, high-carbohydrate diet is not helping them control their blood glucose. As one woman wrote about her experience with a diabetes center:

“I was so frustrated, I quit going to the center for check ups.”

The data suggest a serious problem in science-community interactions which needs to be

explored.

Conclusions & recommendations: Our findings document a large number of such cases pointing to the need for public hearings and or conference. The community is not well served by an establishment that refuses to address its critics from within the general population as well as health professionals.

Figure 4. Some comments from the Active Low-Carber Forums (140, 660 members on March 12, 2012).

Biographies:

Tom Naughton is a former writer for a health magazine, a contributor to the Encylopedia Britannica’s Health and Medical Annual, a documentary filmmaker, and popular blogger who specializes in health and nutrition issues.

Jimmy Moore’s top-rated “Livin’ La Vida Low-Carb” blog has drawn more than 6 million visitors since 2005. His podcast show, “The Livin’ La Vida Low-Carb Show with Jimmy Moore” has featured interviews with hundreds of respected doctors and researcher. He has also authored two books.

Laura Dolson, MS is a writer and cancer support provider at Mediconsult.com, and hastaught health and nutrition classes at a junior high charter school in California. Her About.com nutrition website draws hundreds of thousands of visitors monthly.


Saturated Fat. On your Plate or in your Blood?

Posted: February 22, 2012 in low-carbohydrate diet, saturated fat, triglycerides, Volek-Westman principle
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(Answers to last week’s organic puzzler at the end of this post).

One of the more remarkable results from Jeff Volek’s laboratory in the past few years was the demonstration that when the blood of volunteers was assayed for saturated fatty acids (SFA), those subjects who had been on a very low-carbohydrate diet had lower levels than those on an isocaloric low-fat diet. This, despite the fact that the low-carbohydrate diet had three times the amount of saturated fat as the low-fat diet. How is this possible? What happened to the saturated fat in the low-carbohydrate diet? Well, that’s what metabolism does. The saturated fat in the low-carbohydrate arm was oxidized while (the real impact of the study) the low-fat arm is making new saturated fatty acid. Volek’s former student Cassandra Forsythe extended the idea by showing how, even under eucaloric conditions (no weight loss) dietary fat has relatively small impact on plasma fat.

The essential point of what I now call the Volek-Westman principle — we should be speaking of basic principles because the idea is more important than specific diets where it is impossible to get any agreement on definitions — the principle is that carbohydrate, directly or indirectly through insulin and other hormones, controls what happens to ingested (or stored) fatty acids. The motto of the Nutrition & Metabolism Society is: “A high fat diet in the presence of carbohydrate is different than a high fat diet in the presence of low carbohydrate.” Widely attributed to me, it is almost certainly something I once said although it has been said by others and the studies from Volek’s lab give you the most telling evidence.

The question is critical. Whereas the scientific evidence now establishes that dietary saturated fat has no effect on cardiovascular disease, obesity or anything else, plasma saturated fatty acids can be a cellular signal and if you study the effect of dietary saturated fatty acids under conditions where carbohydrate is high and/or in rodents where plasma fat better correlates with dietary fat, then you will confuse plasma fat with dietary fat. An important study identified potential cellular elements in control of gene transcription that bear on lipid metabolism.

So, it is important to know about plasma saturated fatty acids. First, recall that strictly speaking there are only saturated fatty acids (SFA) — this is explained in detail in an earlier post.  What is called saturated fats simply mean those fats that have a high percentage of SFAs — things that we identify as “saturated fats,” like butter, are usually only 50 % saturated fatty acids (coconut oil is probably the only fat that is almost entirely saturated fatty acids but because they are medium chain length, they are usually considered a special case).

In Volek’s study, 40 overweight subjects were randomly assigned either to a carbohydrate-restricted diet (abbreviated CRD; %CHO:fat:protein = 12:59:28) or to a low fat diet, (LFD; %CHO:fat:protein = 56:24:20). The group was unusual in that they were all overweight would be characterized as having metabolic syndrome, in particular they all had, atherogenic dyslipidemia, which is the term given to a poor lipid profile (high triacylglycerol (TAG), low HDL-C, high small-dense LDL (so-called pattern B)). Metabolic syndrome (MetS) is the predisposition to CVD and diabetes and is characterized by the constellation of overweight, atherogenic dyslipidemia and, by now, a dozen other markers.

The paper is one of the more striking for the differences in weight loss between two diet regimens. Although participants were not specifically counseled to reduce calories, there was a reduction in total caloric intake in both two groups. The response in weight loss, however, due to the difference in macronutrient composition, was dramatically different in the two groups. The CRD group (labelled as very low carbohydrate ketogenic diet (VLCKD) in the figure) lost twice as much weight on average as the low-fat controls despite the similar caloric intake. Although there was substantial individual variation, 9 of 20 subjects in the CRD (VLCKD) group lost 10% of their starting weight. more than that lost by any of the subjects in the LFD group. In fact, nobody following the LFD lost as much weight as the average for the low-carbohydrate group and, unlike George Bray’s demonstration of caloric inefficiency, whole body fat mass was where the major differences between the CRD (VLCKD) and LF appeared (5.7 kg vs 3.7 kg). Of significance is the observation that fat mass in the abdominal region decreased more in subjects on the CRD than in subjects following the LFD (-828 g vs -506 g). This is one of the more dramatic effects of carbohydrate restriction on weight loss but many have preceded it and these have been frequently criticized for increasing the amount of saturated fat (whether or not any particular study actually increased saturated fat). Although the original “concern” was that this would lead to increased plasma cholesterol, eventually saturated fat became a generalized villain and, insofar as any science was involved, the effects of plasma saturated fat were assumed to be due to dietary saturated fat. The outcome of Volek’s study was surprising. Surprising because the effect was so clear cut (no statistics needed) and because an underlying mechanism could explain the results.

Saturated Fat

The dietary intake of saturated fat for the people on the VLCKD (36 g/day) was threefold higher than that of the people on the LFD (12 g/day). When the relative proportions of circulating SFAs in the triglyceride and cholesterol ester fractions were determined, they were actually lower in the low carb group. Seventeen of 20 subjects on the CRD (VLCKD) showed a decrease in total saturates (the others had low values at baseline) in comparison to half of the subjects consuming the LFD had a decrease in saturates. When the absolute fasting TAG levels are taken into account (low carbohydrate diets reliably reduce TAB=G), the absolute concentration of total saturates in plasma TAG was reduced by 57% in the low carbohydrate arm compared to 24% reduction in the low fat arm who had, in fact, reduced their saturated fat intake. One of the saturated fatty acids of greatest interest was palmitic acid or, in chemical short-hand, 16:0 (16 means that there are 16 carbons and 0 means there are no double bonds, that is, no unsaturation).

So how could this happen? The low fat group reduced their SFA intake by one-third, yet had more SFA in their blood than the low-carbohydrate group who had actually increased intake. Well, we need to look at the next thing in metabolism.

In the post on An Introduction to Metabolism, we made the generalization that there were roughly two kinds of fuel, glucose and acetyl-CoA (the two carbon derivative of acetic acid). The big principle in metabolism was that you could make acetyl-CoA from glucose, but (with some exceptions) you couldn’t make glucose from acetyl-CoA, or more generally, you can make fat from glucose but you can’t make glucose from fat. How do you make fat from glucose? Part of the picture is making new fatty acids, the process known as De Novo Lipogenesis (DNL) or more accurately de novo fatty acid synthesis. The mechanism then involves successively patching together two carbon acetyl-CoA units until you reach the chain length of 16 carbons, palmitic acid. The first step is formation of a three carbon compound, malonyl-CoA, a process which is under the control of insulin. Malonyl-CoA starts the process of DNL but simultaneously prevents oxidation of any fatty acid since, if you are making it, you don’t want to burn it. This can be further processed, among other things, can be elongated to stearic acid (18:0). So this is a reasonable explanation for the increased saturated fatty acid in the low-fat group: the higher carbohydrate diet has higher insulin levels on average, encouraging diversion of calories into fatty acid synthesis and repressing oxidation. How could this be tested?

It turns out that, in addition to elongation, the palmitic acid can be desaturated to make the unsaturated fatty acid, palmitoleic acid (16:1-n7, 16 carbons, one unsaturation at carbon 7) and the same enzyme that catalyzes this reaction will convert stearic acid (18:0) to the unsaturated fatty acid oleic acid (18:1n-7). The enzyme is named for the second reaction stearoyl desaturase-1 (SCD-1; medical students always hate seeing a “-1” since they know 2 and 3 may will have to be learned although, in this case, they are less important). SCD-1 is a membrane-bound enzyme and it seems that it is not swimming around the cell looking for fatty acids but is, rather, closely tied to DNL, that is, it preferentially de-saturates newly formed palmitic acid to palmitoleic acid.

There is very little palmitoleic acid in the diet so its presence in the blood is an indication of SCD-1 activity. The data show a 31% decrease in palmitoleic acid (16:1n-7) in the blood of subjects on the low-carb arm with little overall change in the average response in the low fat group. Saturated fat, in your blood or on your plate?

Forsythe’s paper extended the work by putting men on two different weight-maintaining low-carbohydrate diets for 6 weeks. One of the diets was designed to be high in SFA (high in dairy fat and eggs), and the other, was designed to be higher in unsaturated fat from both polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids (high in fish, nuts, omega-3 enriched eggs, and olive oil). The relative percentages of SFA:MUFA: PUFA were, for the SFA-carbohydrate-restricted diet, 31: 21:5, and for the UFA diet, 17:25:15. The results showed that the major changes in plasma SFA and MUFA were in the plasma TAG fraction although probably much less than might be expected given the nearly two-fold difference in dietary saturated fat and, as the authors point out: “the most striking finding was the lack of association between dietary SFA intake and plasma SFA concentrations.”

So although it is widely said that the type of fat is more important than the amount, the type is not particularly important. But, what about the amount? A widely cited paper by Raatz, et al. suggested, as indicated by the title, that ‘‘Total fat intake modifies plasma fatty acid composition in humans”, but the data in the paper shows that differences between high fat and low fat were in fact minimal (figure below).

The bottom line is that distribution of types of fatty acid in plasma is more dependent on the level of carbohydrate then the level or type of fat. Volek and Forsythe give you a good reason to focus on the carbohydrate content of your diet. What about the type of carbohydrate? In other words, is glycemic index important? Is fructose as bad as they say? We will look at that in a future post in which I will conclude that no change in the type of carbohydrate will ever have the same kind of effect as replacing carbohydrate across the board with fat. I’ll prove it.

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Answers to the organic quiz.