The argument in their defense is the same one that Peter Cleave made forty years ago, when he proposed what he cal ed the saccharine-disease hypothesis. Evolution should be our best guide for what const.i.tutes a healthy diet. It takes time for a population or a species to adapt to any new factor in its environment; the longer we've been eating a particular food as a species, and the closer that food is to its natural state, the less harm it is likely to do.

This is an underlying a.s.sumption of al public-health recommendations about the nature of a healthy diet. It's what the British epidemiologist Geoffrey Rose meant when he wrote his seminal 1985 essay, "Sick Individuals and Sick Populations," and described the acceptable measures of prevention that could be recommended to the public as those that remove "unnatural factors" and restore "'biological normality'-that is...the conditions to which presumably we are genetical y adapted." "Such normalizing measures," Rose said, "may be presumed to be safe, and therefore we should be prepared to advocate them on the basis of a reasonable presumption of benefit."

The fat content of the diets to which we presumably evolved, however, wil always remain questionable. If nothing else, whatever const.i.tuted the typical Paleolithic hunter-gatherer diet, the type and quant.i.ty of fat consumed a.s.suredly changed with season, lat.i.tude, and the coming and going of ice ages.

This is the problem with recommending that we consume oils in any quant.i.ty. Did we evolve to eat olive oil, for example, or linseed oil? And maybe a few thousand years is sufficient time to adapt to a new food but a few hundred is not. If so, then olive oil could conceivably be harmless or even beneficial when consumed in comparatively large quant.i.ties by the descendants of Mediterranean populations, who have been consuming it for mil ennia, but not to Scandinavians or Asians, for whom such an oil is new to the diet. This makes the science even more complicated than it already is, but these are serious considerations that should be taken into account when discussing a healthy diet.

There is no such ambiguity, however, on the subject of carbohydrates. The most dramatic alterations in human diets in the past two mil ion years, unequivocal y, are (1) the transition from carbohydrate-poor to carbohydrate-rich diets that came with the invention of agriculture-the addition of grains and easily digestible starches to the diets of hunter-gatherers; (2) the increasing refinement of those carbohydrates over the past few hundred years; and (3) the dramatic increases in fructose consumption that came as the per-capita consumption of sugars-sucrose and now high-fructose corn syrup -increased from less than ten or twenty pounds a year in the mid-eighteenth century to the nearly 150 pounds it is today. Why would a diet that excludes these foods specifical y be expected to do anything other than return us to "biological normality"?

It is not the case, despite public-health recommendations to the contrary, that carbohydrates are required in a healthy human diet. Most nutritionists stil insist that a diet requires 120 to 130 grams of carbohydrates, because this is the amount of glucose that the brain and central nervous system wil metabolize when the diet is carbohydrate-rich. But what the brain uses and what it requires are two different things. Without carbohydrates in the diet, as we discussed earlier (see Chapter 19), the brain and central nervous system wil run on ketone bodies, converted from dietary fat and from the fatty acids released by the adipose tissue; on glycerol, also released from the fat tissue with the breakdown of triglycerides into free fatty acids; and on glucose, converted from the protein in the diet. Since a carbohydrate-restricted diet, unrestricted in calories, wil , by definition, include considerable fat and protein, there wil be no shortage of fuel for the brain. Indeed, this is likely to be the fuel mixture that our brains evolved to use, and our brains seem to run more efficiently on this fuel mixture than they do on glucose alone. (A good discussion of the rationale for a minimal amount of carbohydrates in the diet can be found in the 2002 Inst.i.tute of Medicine [IOM] report, Dietary Reference Intakes. The IOM sets an "estimated average requirement" of a hundred grams of carbohydrates a day for adults, so that the brain can run exclusively on glucose, "without having to rely on a partial replacement of glucose by [ketone bodies]." It then sets the "recommended dietary al owance" at 130 grams to al ow margin for error. But the IOM report also acknowledges that the brain wil be fine without these carbohydrates, because it runs perfectly wel on ketone bodies, glycerol, and the protein-derived glucose.) Whether a carbohydrate-restricted diet is deficient in essential vitamins and minerals is another issue. As we also discussed (see Chapter 19), animal products contain al the amino acids, minerals, and vitamins essential for health, with the only point of controversy being vitamin C. And the evidence suggests that the vitamin C content of meat products is more than sufficient for health, as long as the diet is indeed carbohydrate-restricted, with none of the refined and easily digestible carbohydrates and sugars that would raise blood sugar and insulin levels and so increase our need to obtain vitamin C from the diet. Moreover, though it may indeed be uniquely beneficial to live on meat and only meat, as Vilhjalmur Stefannson argued in the 1920s, carbohydrate-restricted diets, as they have been prescribed ever since, do not restrict leafy green vegetables (what nutritionists in the first half of the twentieth century cal ed 5 percent vegetables) but only starchy vegetables (e.g., potatoes), refined grains and sugars, and thus only those foods that are virtual y without any essential nutrients unless they're added back in the processing and so fortified, as is the case with white bread. A calorie-restricted diet that cuts al calories by a third, as John Yudkin noted, wil also cut essential nutrients by a third. A diet that prohibits sugar, flour, potatoes, and beer, but al ows eating to satiety meat, cheese, eggs, and green vegetables wil stil include the essential nutrients, whether or not it leads to a decrease in calories consumed.

My hope is that this book wil change our views of the nature of a healthy diet, as the research for it changed my own; that future discussions of the nature of a healthy diet wil begin with the quant.i.ty and quality of the carbohydrates contained, rather than the fat. As a chal enge to the conventional wisdom on diet, obesity, and chronic disease, however, it presents a dilemma to public-health authorities; to nutritionists and physicians who believe that the advice they have been giving for the past few decades has been correct and based in sound science; and to al of us who simply want to eat healthy but have trouble accepting that everything we have come to believe could be as misguided as I have portrayed it. The resolution to this dilemma is to test the carbohydrate hypothesis rigorously, just as the fat-cholesterol hypothesis of heart disease should have been tested forty years ago.

In the past decade, the National Inst.i.tutes of Health final y began funding randomized-control trials of carbohydrate-restricted diets, as has the Dr.

Robert C. Atkins Foundation, but these trials have been designed to test only the hypothesis that such diets can be used safely and effectively as a means to lose weight. The subjects are overweight and obese, and the studies compare weight loss and heart-disease risk factors with the results of low-fat or calorie-restricted diets. These trials are neither planned nor interpreted as tests of the hypothesis that it is the carbohydrates in the diet-"the sugar and starchy elements of food," as The Lancet phrased it 140 years ago-that cause fattening and obesity to begin with. Rather, the underlying a.s.sumption here, too, is that weight loss is caused inevitably by negative caloric balance-consuming fewer calories then we expend-and the investigators perceive these trials as testing whether carbohydrate restriction al ows us to do so with more or less facility than semi-starvation diets that reduce calories directly or reduce fat calories specifical y.

A direct test of the carbohydrate hypothesis asks the opposite question: not whether the absence of refined and easily digestible carbohydrates and sugars causes weight loss and is safe, but whether the presence of these carbohydrates causes weight gain and chronic disease. Such a trial would ideal y be done with lean, healthy individuals, or with a spectrum of subjects from lean through obese, including those with metabolic syndrome and Type 2 diabetes. They would be randomized into two groups, one of which would consume the sugary and starchy elements of food and one of which would not, and then we would see what happens. We might randomly a.s.sign a few thousand individuals to eat the typical American diet of today-including its 140 50 pounds of sugar and high-fructose corn syrup a year, nearly 200 pounds of flour and grain, 130-plus pounds of potatoes, and 27 pounds of corn-and we could a.s.sign an equal number to eat a diet of mostly animal products (meat, fish, fowl, eggs, cheese) and leafy green vegetables. Since the latter diet would be relatively high in fat and saturated fat and calorical y dense, the conventional wisdom is that it would cause heart disease and, perhaps, obesity and diabetes. So this would test the dietary-fat/cholesterol hypothesis of heart disease, as wel as the carbohydrate hypothesis.

Such a trial would not be ideal, because many dietary variables would differ between the two groups-calories and fats among them. The subjects would also know what diet they're consuming, and so the study would not be done blindly (although, ideal y, the physicians who treated the subjects and the investigators themselves would be unaware). Nonetheless, it would be a good starting point. Would those eating the carbohydrate-rich diet be more likely to become glucose-intolerant, hyperinsulinemic, and insulin-resistant? Would they be fatter and have a greater incidence of obesity, metabolic syndrome, and Type 2 diabetes? Would they have more heart disease and cancer? Would they die prematurely or live longer? These are the questions we need to answer.

Another question that needs to be addressed urgently regards the health effects of sugar and high-fructose corn syrup alone. Since the 1980s, as we discussed (see Chapter 12), sugar and high-fructose corn syrup have been exonerated as causes of chronic disease on the basis that the evidence was ambiguous. Since then, virtual y no studies have been funded; there have been no attempts to clarify the picture. Today I can imagine no research more important to the public health than rigorous, control ed trials of the long-term health effects of sugar and high-fructose corn syrup.

For the past decade, the National Inst.i.tutes of Health has been funding trials that test whether "lifestyle modification" wil prevent diabetes and metabolic syndrome. But these trials are done only in the context of the conventional wisdom on diet, obesity, and disease. In the largest of these trials to date, the $150 mil ion Diabetes Prevention Program, the lifestyle modification included 150 minutes of exercise each week and a low-fat, low-calorie diet. The results confirmed that such a program of diet and exercise wil indeed prevent or delay the appearance of diabetes and metabolic syndrome, but they said nothing about what aspect of this lifestyle modification was responsible. Was it the reduction in fat calories or total calories? Was it the exercise? Or was it a change in the type of carbohydrates consumed or a reduction in the total amount of carbohydrates? As we discussed (see Chapter 19), even if the goal of a diet is to reduce calories by preferential y reducing fat, it wil inevitably cut back on carbohydrates as wel , and usual y sugars in particular.*138 The NIH is currently spending $200 mil ion on a decade-long trial cal ed Look AHEAD to test the hypothesis that if obese diabetics lose weight they'l be healthier for the effort. This is "the largest, most expensive trial ever funded by NIH for obesity outcome research," says the Baylor University psychologist John Foreyt, who is one of the trial's princ.i.p.al investigators. But once again, the trial tests only the conventional wisdom. The goal of Look AHEAD is to induce five thousand obese diabetics to lose weight by the same lifestyle modification used in the Diabetes Prevention Program: cutting calories and fat calories, and exercising. If these obese diabetics do lose weight, and if they do end up healthier for it, we stil won't know whether it was the calories, the fat calories, the exercise, some combination of al three, or maybe just the carbohydrates or the sugar that made the difference. And we won't know whether, if they restricted carbohydrates alone and ate protein and fat to their hearts' content, they would have been healthier stil .

Because these trials are planned as a test of only one hypothesis-and a poorly defined hypothesis at that-the research ensures that we won't have the kind of reliable answers that we so desperately need. If the Diabetes Prevention Program had included a test of the carbohydrate hypothesis, the investigators could have compared the effect of a low-fat, low-calorie diet and exercise to the effect of carbohydrate restriction alone, and that would have told us whether it's the carbohydrates or the calories and the sedentary behavior that cause these chronic diseases. If Look AHEAD were to include a test of the carbohydrate hypothesis, we might at least know the answer in another decade. It doesn't, and we won't.

The scientific obligation, as I said in the prologue, is to establish the cause of obesity, diabetes, and the chronic diseases of civilization beyond reasonable doubt. By doing so, we can take the necessary steps to prevent these disorders, rather than trying to cure them or ameliorate them after the fact. If there are competing hypotheses, it does us little good to test one alone. It does little good to continue basing public-health recommendations and dietary advice on a.s.sociation studies (the Framingham Heart Study and the Nurses Health Study are prominent examples) that are incapable of reliably establishing cause and effect. What's needed now are randomized trials that test the carbohydrate hypothesis as wel as the conventional wisdom. Such trials would be expensive. Like the Diabetes Prevention Program and Look AHEAD, they'l cost tens or hundreds of mil ions of dol ars. And even if such trials are funded, it might be another decade or two before we have reliable answers. But it's hard to imagine that this controversy wil go away if we don't do them, that we won't be arguing about the detrimental role of fats and carbohydrates in the diet twenty years from now. The public wil certainly not be served by attempts of interest groups and industry to make this controversy go away. If the tide of obesity and diabetes continues to rise around the world, it's hard to imagine that the cost of such trials, even a dozen or a hundred of them, won't ultimately be trivial compared with the societal cost.

Notes.

PROLOGUE: A BRIEF HISTORY OF BANTING.

Epigraph. "Farinaceous...": Tanner 1869b:219.

"...corpulence notoriety": Anon. 1864b. "...size or weight": Banting 1864:14.

"Knowing too that...": Harvey 1872:6970.

Banting began dieting: Banting 1864:1819. "I have not felt better...": Banting 1869.

United States, Germany: Banting 1869. "the emperor of the French...": Anon. 1864c. "If he is gouty...": Quoted in "banting" entry, OED 1989.

A paper was presented: Anon. 1864f. See also Anon. 1864d; Anon. 1864a. "is tolerably complete...": Anon. 1864g. Banting responded: Banting 1869.

Banting acknowledged: Banting 1869. Alfred Wil iam Moore: Anon. 1864g. John Harvey: Harvey 1864.

Bril at-Savarin: Bril at-Savarin 1986 ("fat...," 23739; "...rigid abstinence...," 251).

Dancel: Dancel 1864 ("Al food...," 59; "The hippopotamus...," 54).

"We advise Mr. Banting...": Anon. 1864g.

"fair trial" and "...starchy elements...": Anon. 1864e.

"To attribute obesity...": Mayer 1968:6.

Sir Wil iam Osler: Osler 1901:43940. Oertel prescribed a diet: Oertel 1895. See also French 1907:951. Bismarck lost sixty pounds: Schwartz 1986:103 4. Ebstein insisted: Ebstein 1884 ("of meat every kind...," 33).

"Foods to be avoided...": Greene 1951:348.

"The great progress...": Bruch 1957:352.

"The overappropriation...": French 1907:14. Rony reported: Rony 1940 ("...marked preference...," 59; "an extremely obese laundress...," 62).

"In Great Britain obesity...": Davidson and Pa.s.smore 1963:382.

"On the day of the races...": Tolstoy 2000:200. "the dearth of proteins...": Lampedusa 1988:255.

What Dr. Spock taught: Spock 1946:361; Spock 1957:436; Spock 1968:449; Spock 1976:493; Spock 1985:536; Spock and Rothenberg 1992:380. 50 mil ion copies: Pace 1998. "Al popular 'slimming regimes'...": Davidson and Pa.s.smore 1963:389. "The first thing...": Brody 1985:18.

Brody recommending potatoes, etc.: Brody 1985:1820. "We need to eat...": Brody 1981a:97. "...at the height of fashion...": Brody 1985:78. "the previous nutritional advice...": James 1983:20. Footnote. See Barr et al. 1953b; Eppright et al. 1955; Blix 1964; Wilson 1969; McLean, Baird, and Howard 1969; Apfelbaum 1973.

"bizarre concepts...": Anon. 1973:1419.

Charlotte Young: C. M. Young 1976 ("The diets developed by Ohlson...," 364; "No adequate explanation...," 365).

"people who cut down...": Squires 1985.

"sparingly": USDA 1992.

"There is always an easy solution...": Mencken 1982:443.

Less red meat, fewer eggs: Putnam et al. 2002. Fat intake has dropped: USDA Center for Nutrition Policy and Promotion 1998. Fal in cholesterol levels: Gregg et al. 2005.

Ten-year study of heart-disease mortality: Rosamond et al. 1998. See also Rosamond et al. 2001; McGovern et al. 2001. AHA statistics: Thom et al.

2006.

Percentage of smokers has dropped: National Center for Health Statistics 2004.

Incidence of obesity increasing: National Center for Health Statistics 2005:9, 275 (table 73). Diabetes rates: Fox et al. 2006; Cowie et al. 2006.

"What we see instead...": Interview, Wil iam Harlan.

Best-sel ing diet books: Mackarness 1958; Tal er 1961; Stil man and Baker 1968; Atkins 1972; Tarnower and Baker 1978; Sears and Lawren 1995; Eades and Eades 1996; Steward et al. 1998; Agatston 2003.

Fixated on cholesterol: This idea came from David Kritchevsky, who, among other accomplishments, auth.o.r.ed the first textbook on cholesterol, published in 1958.

Series of expert reports: USDA and USDHEW 1980; USDHHS 1988; NRC 1989; U.K. Department of Health 1994.

"Each science...": Whitehead 1980:1415.

"If science is to progress...": Feynman 1967:148.

PART ONE: THE FAT-CHOLESTEROL HYPOTHESIS.

Epigraph. "Men who have excessive faith...": Bernard 1957:38.

CHAPTER ONE:.

THE EISENHOWER PARADOX.

Epigraph. "In medicine...": Bernard 1957:55.

The details of Eisenhower's heart attack: Lasby 1997:7080.

White's press conference and Ike's recovery: Ibid.:8393.

Eisenhower's weight, cholesterol, and blood pressure: Ibid.:25758; interview, George Mann.

Ten times a year: Lasby 1997:70. Eisenhower's diet and Snyder's responses: Ibid.:25859.

"He eats nothing...": Ibid.

"He was fussing...": Ibid.:260.

Keys made the cover of Time: Anon. 1961 ("...know the facts," 52). First official endors.e.m.e.nt: AHA 1961.

Eisenhower's half-dozen heart attacks: Lasby 1997:293323.

"great epidemic": White 1971:220.

"drastic development...": Mayer 1975a:138. Decline in deaths due to eating less fat: See, for instance, Sykowski et al. 1990; Hunink et al. 1997; NCEP 2002:I 26.

Osler wrote in 1910: Cited in Ca.s.sidy 1946. "If it had been common...": White 1971:52. "part and parcel..." and "...cripples and kil s...": White 1945:475.

Herrick, the ECG, and the early history of cardiology: Liebowitz 1970:14676. "Medical diagnosis..." and "...after the publication...": Levy 1932.

Census numbers: Cooper 1972; Preston et al. 1972. Fortune article: Anon. 1950. Ca.s.sidy's point: Ca.s.sidy 1946.

Mitigating against the "epidemic": Levy 1932. See also Tunstal Pedoe 1984.

AHA 1957 report: Page et al. 1957 ("great difference...," 165).

Between 1949 and 1968: Harper 1996. See also Harper 1983. Proportion of heart-disease deaths dropping: Harper 1996; interviews, Harry Rosenberg, chief of mortality statistics, National Center for Health Statistics, and Thomas Thom, a statistician at the National Heart, Lung, and Blood Inst.i.tute. WHO committee report: Lozano et al. 2001 ("...the apparent increase...," 14). About the situation in the United States, see also Woolsey and Moriyama 1948.

NHI 1949 al ocations: Haseltine 1949. NHI 1960 research budget is from NIH, n.d., NIH Almanac.

"a private organization...": White 1971:114. 1945 charitable contributions: Anon. 1945. Rome Betts: Moore 1983:57.

AHA fund-raising campaign and its success: Anon. 1948a; Anon. 1948b; Davies 1950; Moore 1983:77. "great epidemic...": White 1971:220.

Compel ing arguments: Mann 1957; Page et al. 1957; Harper 1983. "un.o.bserved publications": Kritchevsky 1992. "They don't fit...": Interview, David Kritchevsky.

"The present high level...": Keys 1953.

"The simple fact...": Select Committee 1977a:1. CSPI pamphlet: Brewster and Jacobson 1978. "Within this century...": Brody 1985:2.

Keys's argument: Keys 1953.

History of food disappearance statistics: USDA 1953; Cal and Sanchez 1967.

"Until World War I ...": Interview, David Cal .

Historians of dietary habits: See, for instance, Schwartz 1986:46; c.u.mmings 1940:1024. One French account: Levenstein 1999. USDA 1830s estimate: Appen 1933, cited in c.u.mmings 1940:15. "with plenty of beef-steaks...": Trol ope 1932.

"considered by the general public...": Ward 1911.

FTC report: FTC 1919 ("...the amount of meat consumed...," 84).

"nationwide propaganda...": Stiebeling 1939.12 The Jungle: Sinclair 2003 ("overlooked for days...," 91). Meat sales dropped by half: Young 1981. "The effect was long-lasting...": Root and de Rochemont 1995:211.

Trends for vegetables, fruits, etc.: USDA 2000.

"The preponderance of meat...": Clendening 1936:7.

Food consumption from the end of World War I : Friend et al. 1979.

"medical vil ain cholesterol": Blakeslee and Stamler 1966:28.

"biological rust...": Ibid. 1966:24.

Anitschkow reported: Anitschkow and Chalatow 1913. The problem with rabbits as animal models: See, for instance, Ahrens, Hirsch, et al. 1957; Altshule 1966. "...'cholesterol disease...": Leary 1935.

Stamler's chicken experiments: Blakeslee and Stamler 1966:36. Natural y occurring atherosclerosis: Altshule 1966; Lindsay and Chaikoff 1963. In baboons: McGil et al. 1960.