The elusive truth part 2: Supplements, diet, fat, and more

In the previous entry, I wrote about how lots of reported scientific findings are later found to be false. In no field is this more evident to the lay public than in the field of nutrition—specifically, dietary advice. In the 1973 Woody Allen film Sleeper, the protagonist is cryogenically frozen in 1973 and wakes up 200 years later and learns that cream pies and hot fudge are good for you. In looking over the landscape of nutritional advice during the last few decades, I start to wonder if Sleeper might not be all that far-fetched.

It wasn’t that long ago that we were told that taking beta-carotene supplements was good for us, that doing so would lower our risk of getting many types of cancer. It had become standard nutritional advice. However, two prospective, controlled, double-blind studies with thousands of subjects in the 1990s showed the exact opposite. One of them, which looked at beta carotene and vitamin E supplementation in over 29,000 male smokers (at high risk for the types of cancer that beta carotene was thought to protect against) found that those who took beta carotene had a higher risk of developing lung cancer than those who didn’t. (The risk of other types of cancer was not significantly affected.) Death from heart attacks and strokes were higher as well among the beta carotene takers [1]. The other study, which looked at the effects of taking a combination of beta carotene and vitamin A supplements, and enrolled over 18,000 smokers, ex-smokers, and workers exposed to asbestos, found that the supplement takers had a 28% greater risk of lung cancer during the four years of the study (halted early due to the strong negative result that was already evident) and a 26% increased risk of death from cardiovascular disease [2]. Neither of these studies suggests in any way that eating foods rich in beta carotene is bad for you, and there’s a heap of evidence that these foods are good for you. But taking beta carotene supplements―well, maybe it’s not such a great idea.

What about the dictum to eat less saturated fat, because it raises the risk of cardiovascular disease and stroke, as well as packing on the pounds? Well, even that venerable advice is under assault. Leading the charge is science journalist Gary Taubes, a contributing correspondent for the journal Science. He lays out his case against the standard dietary advice in two books: Good Calories, Bad Calories (Anchor Books, 2008; owned by the University of Regina Library), a thick tome that examines diet in relation to disease and obesity, and Why We Get Fat (Alfred A. Knopf, 2011; owned by the U of R Library), a relatively slimmer book that, as the title implies, focuses more specifically on obesity.

To summarize greatly, Taubes makes the case for the following assertions:

·         The primary driver of obesity and, more generally, metabolic syndrome (obesity, insulin resistance, high blood pressure, high triglycerides) is excess carbohydrate consumption, especially refined carbohydrates.

·         Eating fatty foods does not make you fat. Fat in your diet does not correspond to fat in your fat cells.

·         Exercise does not help you lose weight or keep it off. Exercise is vital for your health, but it doesn’t help you with your weight.

·         For people who are prone to obesity, a very low-carbohydrate Atkins-style diet may be a good way to help keep weight under control.

 

·         Fat, including saturated fat (but with the notable exception of artificial trans fat), is blameless in the development of cardiovascular disease.

·         Counting calories is pointless.

In regard to the last point, Taubes is scornful of authorities who insist that “calories in vs. calories out” is a key concept in overweight and obesity. Such assertions seem to imply that you simply lower your intake of calories and increase your exercise, and voilà, your weight problem is solved. If only it were that simple. As Taubes explains, fat is always moving in and out of fat cells. In obese people, the cells tend to suck in fat from the bloodstream and hold onto it more tenaciously than do the fat cells of slim people. In other words, obesity is the result of the body’s dysregulated management of fat, and in Taubes’s telling, excess consumption of carbohydrates, especially refined ones, is a prime cause of this dysregulation.

In regard to the “standard line” on saturated fat, that it causes atherosclerosis, which causes cardiovascular and cerebrovascular disease, Taubes says that it’s all wrong. He goes into a great deal of detail in Good Calories Bad Calories on the history of thinking and research in this area. He places the lion’s share of the blame for this incorrect (according to Taubes) line of thinking on Ancel Keys, a University of Minnesota physiologist, who, says Taubes, became convinced of the saturated fat-atherosclerosis hypothesis in the 1950s, and from then on looked favourably on research that supported his hypothesis and heaped scorn upon any that tended to contradict it―and heaped scorn as well upon researchers who disagreed with him. Through the force of his domineering will and personality he made his view into the conventional wisdom.

An interesting fact about Ancel Keys’s life, which Taubes doesn’t mention, is that he was one of the children who were selected by Stanford University psychologist Lewis Terman for his life-long study of gifted children. This study, which continued on after Terman’s death, followed the children for the rest of their lives; most of them have died by now. A fascinating book about this is Terman’s Kids, by Joel N. Shurkin (Little, Brown, 1992; owned by the U of R Library). Keys is one of several subjects in Terman’s study who are featured in the book. In it, Keys comes across as productive, intellectually curious, possessed of a driving energy, and impatient. Shurkin writes of him, “His work has probably had greater influence on our welfare than the work of any other person in Terman’s study.” (page 250) Taubes doubtless would agree, but not in the positive way that Shurkin meant.

Another interesting fact about Keys is that he lived to be 100 years old, dying in 2004. Make what you will of that.

Taubes writes persuasively and backs up his arguments with loads of references to the literature, but I personally am not entirely ready to consider myself a convert. As you can imagine, the books have generated some controversy. In my own personal experiment with N=1, I’ve found that whenever I’ve decided, for health reasons, to add nuts (low carbohydrate, high fat^†) as a regular part of my diet, my belt gets tighter. Still, Taubes did completely convince me of one thing: that the standard advice and conventional wisdom about diet and its relation to weight and disease rests upon a surprisingly tenuous foundation. There is a tremendous amount we don’t know about obesity, metabolic syndrome, and disease, and their relationship with diet and other lifestyle factors. It will be fascinating to see how all this unfolds in the years to come.

There is one thing we can count on: many of the “facts” that will be uncovered as research in this area progresses will be short-lived.

^† The label on a jar of mixed nuts in my kitchen says that a ¼ cup serving contains 7 grams of carbohydrate, which is less than one-fourth as much as in a bowl of oatmeal with a cup of whole milk, and 18 grams of fat, almost twice as much as that bowl of oatmeal with whole milk.

 

REFERENCES

[1] The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group. (1994). “The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers.” New England Journal of Medicine, 330(15), 1029-1035. DOI: 10.1056/NEJM199404143301501

[2] Omenn, Gilbert S., Gary E. Goodman, et al. (1996). “Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.” New England Journal of Medicine, 334(18), 1150-1155. DOI: 10.1056/NEJM199605023341802

The elusive truth: Shifting scientific findings

How lasting are scientific findings? In the previous blog post, I quoted Simon LeVay from his book, When Science Goes Wrong, where he suggests that it would be interesting to look at a random collection of scientific papers from a couple of decades or so ago and ask, “Were they right in their main findings and conclusions, and were they as original as their authors claimed?” This post will deal with the first question.

This topic has been receiving some attention in the past few years, especially in the fields of medicine and nutrition. Two years ago The Atlantic magazine ran a fascinating feature article on John Ioannidis, a Greek medical school professor, who has made a career of studying the staying power of medical research findings (Freedman, D. H. “Lies, damned lies, and medical science.” The Atlantic, 306(4), p. 76-86, Nov. 2010). In a nutshell, what he has discovered is that for medical articles, the answer to LeVay’s question, “Were they right in their main findings and conclusions”, is usually no. In fact, Ioannidis came to prominence with the publication of a thorough analysis in PLOS Medicine with the blunt title, “Why most published research findings are false” (vol. 2(8), e-page e124, 2005, DOI: 10.1371/journal.pmed.0020124). He comes to several interesting conclusions, including “The greater the financial and other interests and prejudices in a scientific field, the less likely the research findings are to be true,” (perhaps not so surprising) and “The hotter a scientific field (with more scientific teams involved), the less likely the research findings are to be true.”

Way back in 1972, physician-author William A. Nolen had something interesting and revealing to say about medical research results in his book A Surgeon’s World (Random House, 1972):

There is, however, one trap into which doctors engaged in research fall with some frequency: that of deciding prematurely that what they want to be true is true. They formulate some theory that sounds interesting, and which if true, will be of great value to medicine, and then set out to prove it is true. In the university hospitals it's sort of a joke—which, like most jokes, has an element of truth to it—that when the professor sends his interns and residents into the dog lab to investigate one of his new ideas, it's their job to prove he's correct. The assistant resident who comes out of the dog lab with a pile of data proving that the professor's theory is all wet is not apt to become chief resident. [pp. 240-241]

(This book is one of my favorites from way back, but unfortunately we do not have it at the University of Regina library and it’s out of print. You can, however, get it through interlibrary loan.)

A related phenomenon which has been seen in many fields is the decline effect, where the strength of research findings appears to decline over time. For example, the therapeutic power of some medicines has seemed to diminish as time has passed. A fascinating aspect of this phenomenon is that individual researchers sometimes see this in their own research as they continue to study an observed effect. An article in the New Yorker by Jonah Lehrer (he of fabricated-Dylan-quotes fame; see the previous blog entry) discusses this in detail (“The truth wears off,” Dec. 13, 2010). Many explanations have been proposed, but whether any of them, or all of them together, are sufficient to explain the decline effect, is very much open to question.

In an article in Nature, University of California-Santa Barbara psychology professor Jonathan Schooler, who has personally experienced the decline effect in his own research, proposes a database that would help get a handle on the mystery. He includes this intriguing tidbit: “Although the laws of reality are usually understood to be immutable, some physicists, including Paul Davies, director of the BEYOND: Center for Fundamental Concepts in Science at Arizona State University in Tempe, have observed that this should be considered an assumption, not a foregone conclusion.” (Schooler, J. “Unpublished results hide the decline effect.” Nature, 470(7335), p. 437, Feb. 24, 2011.) The universe might be stranger than we think.

Scientific misadventure: A review of When Science Goes Wrong, by Simon LeVay

In a well-rounded university library collection, some of the books—the majority of them—directly support the research and educational programs of the university. Others can be considered food for thought. They provide stimulation for inquiring minds, a way to explore new areas and expand one’s horizon. Many of these are just plain fun to read. I will review some from time to time that have piqued my interest, starting now.

If you are fascinated by science and technology, you would probably enjoy When Science Goes Wrong: Twelve Tales from the Dark Side of Discovery, by Simon LeVay (Penguin Group, 2008, in the Archer Library at call number Q 172.5 E77 L48 2008). There are twelve chapters that can be read individually, each telling of an episode that involved science or technology, and in which something went terribly wrong. The subject matter of the stories ranges all over the map: a highly experimental and unauthorized transplant of fetal tissue into a Parkinson’s patient’s brain, an explosion at a nuclear power plant (eighteen years before Three Mile Island), geologists killed as they explored an active volcano that became too active at the wrong moment, out-and-out scientific fraud, and eight others just as diverse.

The author, Simon LeVay, is a neuroscientist who briefly came to fame back in 1991 when he published, as a sole author in the journal Science, the first study to document a structural difference between the brains of gay and straight men (LeVay, S. A difference in hypothalamic structure between heterosexual and homosexual men. Science, 253(5023), p. 1034-1037, August 30, 1991, DOI: 10.1126/science.1887219). He came to popular science writing only after a career at the prestigious Salk Institute for Biological Studies in San Diego and Harvard Medical School. This background is reflected in his writing, which is the writing of a true scientist. It is not flashy, but not plodding. The writing carefully focuses on the science, on the facts, on what is known and what is not known. In this book, you certainly won’t find anything like Malcolm Gladwell’s “igon values” (eigenvalues), or Jonah Lehrer’s manufactured Bob Dylan quotes. This style will probably never get one of LeVay’s books on the bestseller list, but it is a style that I think will engage most scientifically-minded readers.

Is there a moral to the book? I didn’t find one, and I don’t think LeVay intended there to be one. Some chapters—maybe most—could be considered cautionary, but not really in some all-encompassing sense, or in the sense of illustrating some grand principle, other than that we should always keep Murphy’s Law in mind. (Indeed, the chapter on the nuclear power plant disaster shows us how astonishingly easy it was to blow up the plant accidentally or intentionally, and the explosion might possibly have been a murder-suicide; the plant was practically an engraved invitation to Murphy. Let’s hope that it’s a bit harder to blow up today’s nuclear plants.) I think what LeVay intended the book to be, and what I found it to be, is simply an interesting read.

LeVay does, however, engage in a bit of rambling philosophizing in a 6-page epilogue. He talks about risk-taking in scientific progress, and writes, “Many risk-taking scientists never make great discoveries, certainly, but few scientists make great discoveries without taking great risks...” Interestingly, a recent issue of Nature touches on this topic in an obituary of Martin Fleischmann, of cold fusion notoriety. For those who don’t remember the cold fusion fiasco, twenty-two years ago Fleischmann and fellow electrochemist Stanley Pons announced triumphantly at a press conference that they had succeeded in generating nuclear fusion using cheap, simple table-top apparatus, in contrast to the billions of dollars that had been spent over decades in the quest for this type of power. The claimed success of Fleischmann and Pons’s process has never been replicated, despite the best efforts of many researchers. It is not generally believed that they engaged in any deception or fraud, but rather that they were too eager to make a dramatic announcement of their results and didn’t sufficiently check for errors. The Nature obituary, after noting a couple of Fleischmann’s scientific successes prior to the cold fusion episode, says that “Cold fusion was not really an aberration for Fleischmann, but an extreme example of his willingness to suggest bold and provocative ideas, to take risks and to make imaginative leaps that could sometimes yield a rich harvest.” (Ball, P. Martin Fleischmann (1927-2012). Nature 489(7414), p. 34, September 6, 2012, DOI: 10.1038/489034a).

LeVay also muses in the epilogue, “It would be an interesting exercise to go back in the scientific literature—say, twenty years or so—and pick a random selection of a hundred papers and ask, ‘Were they right in their main findings and conclusions, and were they as original as their authors claimed?’ I’ll write more about this in a future post.