Good Calories, Bad Calories (28 page)

It wasn’t until the late 1990s that the evolving science of metabolic syndrome began to have any significant influence outside the field of diabetes, at which point the media final y began to take notice.†40 The potential implications of metabolic syndrome for heart disease and other chronic diseases have only just begun to be appreciated by the research community. As a result, a hypothesis that emerged from research in the 1950s as an alternative explanation for the high rates of heart disease in Western nations has been accepted by medical researchers and public-health authorities a half-century later as a minor modification to Keys’s dietary-fat/cholesterol hypothesis, even though this alternative hypothesis implies that Keys’s hypothesis is wrong. The bulk of the science is no longer controversial, but its potential significance has been minimized by the assumption that saturated fat is stil the primary evil in modern diets.

The Tokelau experience stands as an example. The current accepted explanation for the pattern of disease among the Tokelauans is that the increased sugar and flour in their diets caused metabolic syndrome, and in turn heart disease and diabetes, at least according to Scott Grundy, who is a nutritionist and specialist in the metabolism of blood lipids at the University of Texas Southwestern Medical Center and the primary author of the 2003 cholesterol guidelines published by the National Cholesterol Education Program (NCEP). This does not mean, however, that Grundy believes that Cleave’s saccharine-disease hypothesis of chronic disease is correct, or that Keys was incorrect. Rather, as he explained it, in the United States the situation was less straightforward than in Tokelau. “What you’re faced with,” Grundy said, “is a historical change in people’s habits. Going back to the 1940s, ’50s, and ’60s, people ate huge amounts of butter and cheese and eggs, and they had very high LDL levels [the “bad cholesterol”] and they had severe heart disease early in life, because of such high cholesterol levels. What’s happened since then is, there has been a change in population behavior, and they don’t consume such high quantities of saturated fat and cholesterol anymore, and so LDL has come down a great deal as our diets have changed. But now…we have got obesity, and most of the problem is due to higher carbohydrate consumption or higher total calories. And so we’re switching more to metabolic syndrome.”

Grundy’s explanation is a modern version of the changing-American-diet story, in this case invoked as a rationale to explain how metabolic syndrome could be the primary cause of heart disease today, while Keys’s hypothesis could stil be correct, but no longer particularly relevant to our twenty-first-century health problems. Grundy’s explanation al ows both Keys and Cleave to be right—by suggesting that their hypotheses addressed two different but relevant nutrition transitions—and therefore does not require that we question the credibility of our public-health authorities. His explanation might be valid, but it relies on a number of disputable assumptions and a selective interpretation of the evidence. It could also be true that we faced very much the same problem fifty years ago that we do today, and that a continuing accumulation of evidence exonerates the fats in the diet and incriminates refined, easily digestible carbohydrates and starches instead. The implications are profound.

The appropriate response to any remarkable proposition in science is extreme skepticism, and the carbohydrate hypothesis of chronic disease offers no exception. But looking at the hypothesis in the context of a concept cal ed homeostasis, which is of fundamental importance for understanding the nature of living organisms, gives us great insight. Much of the progress in physiology in the mid-twentieth century could be described as the transferral of this “concept of the nature of the wholeness,” as the Nobel Laureate chemist Hans Krebs suggested in 1971, “from the realm of philosophy and theory of knowledge to that of biochemical and physiological experimentation.” Though physiologists were aware of this paradigmatic shift, clinical investigators studying chronic disease have paid little attention, which means that the greater implications of the fundamental idea of homeostasis have been slighted.

In the mid-nineteenth century, the legendary French physiologist Claude Bernard observed that the fundamental feature of al living organisms is the interdependence of the parts of the body to the whole. Living beings are a “harmonious ensemble,” he said, and so al physiological systems have to work together to assure survival. The prerequisite for this survival is that we maintain the stability of our internal environment, the milieu intérieur, as Bernard famously phrased it

—including a body temperature between 97.3°F and 99.1°F and a blood-sugar level between 70 mg/dl and 170 to 180 mg/dl—regardless of external influences. “Al the vital mechanisms, however varied they may be,” Bernard wrote, “have only one object, that of preserving constant the conditions of life in the internal environment.” (As the British biologist J.B.S. Haldane noted a half-century later, “No more pregnant sentence was ever framed by a physiologist.”) And this stability of the milieu intérieur is accomplished, Bernard said, by a continual adjustment of al the components of this living ensemble “with such a degree of perfection that external variations are instantly compensated and equilibrated.”

In 1926, Bernard’s concept was reinvented as homeostasis by the Harvard physiologist Walter Cannon, who coined the term to describe what he cal ed more col oquial y “the wisdom of the body.” “Somehow the unstable stuff of which we are composed,” Cannon wrote, “had learned the trick of maintaining stability.” Although “homeostasis” technical y means “standing the same,” both Cannon and Bernard envisioned a concept more akin to what systems engineers cal a dynamic equilibrium: biological systems change with time, and change in response to the forces acting on them, but always work to return to the same equilibrium point—the roughly 98.6°F of body temperature, for instance. The human body is perceived as a fantastical y complex web of these interdependent homeostatic systems, maintaining such things as body temperature, blood pressure, mineral and electric-charge concentration (pH) in the blood, heartbeat, and respiration, al sufficiently stable so that we can sail through the moment-to-moment vicissitudes of the outside world. Anything that serves to disturb this harmonic ensemble wil evoke instantaneous compensatory responses throughout that work to return us to dynamic equilibrium.

Al homeostatic systems, as Bernard observed, must be amazingly interdependent to keep the body functioning properly. Maintaining a constant body temperature, for example, is critical because biochemical reactions are temperature-sensitive

—they wil proceed faster in hotter temperatures and slower in colder ones. But not al biochemical reactions are equal y sensitive, so their rates of reaction wil not change equal y with changes in temperature. A biological system like ours that runs ideal y at 98.6°F can spin out of control when this temperature changes and al the myriad biochemical reactions on which it depends now proceed at different rates. Our body temperature is the product of the heat released from the chemical reactions that constitute our metabolism. It is balanced in turn by the cooling of our skin in contact with the outside air. On cold days, we wil metabolical y compensate to generate more heat, and so more of the calories we consume go to warming our bodies than they would on hot days. Thus, the ambient temperature immediately affects, among other things, the regulation of blood-sugar and of carbohydrate and fat metabolism. Anything that increases body heat (like exercise or a hot summer day) wil be balanced by a reduction of heat generated by the cel s, and so there is a decrease in fuel use by the cel s. It wil also be balanced by dehydration, increased sweating, and the dilation of blood vessels near the surface of the skin. These, in turn, wil affect blood pressure, so another set of homeostatic mechanisms must work, among other things, to maintain a stable concentration of salts, electric charge, and water volume. As the volume of water in and around the cel s decreases in response to the water lost from sweating or dehydration, our bodies respond by limiting the amount of water the kidneys excrete as urine and inducing thirst, so we drink water and replenish what we’ve lost. And so it goes. Any change in any one homeostatic variable results in compensatory changes in al of them.

This whole-body homeostasis is orchestrated by a single, evolutionarily ancient region of the brain known as the hypothalamus, which sits at the base of the brain. It accomplishes this orchestral task through modulation of the nervous system

—specifical y, the autonomic nervous system, which controls involuntary functions—and the endocrine system, which is the system of hormones. The hormones control reproduction, regulate growth and development, maintain the internal environment—i.e., homeostasis—and regulate energy production, utilization, and storage. Al four functions are interdependent, and the last one is fundamental to the success of the other three. For this reason, al hormones have some effect, directly or indirectly, on fuel utilization and what’s known technical y as fuel partitioning, how fuel is used by the body in the short term and stored for the long term. Growth hormone, for example, wil stimulate the mobilization of fat from fat cel s to use as energy for cel repair and tissue growth.

Al other hormones, however, are secondary to the role of insulin in energy production, utilization, and storage. Historical y, physicians have viewed insulin as though it has a single primary function: to remove and store away sugar from the blood after a meal. This is the most conspicuous function impaired in diabetes. But the roles of insulin are many and diverse. It is the primary regulator of fat, carbohydrate, and protein metabolism; it regulates the synthesis of a molecule cal ed glycogen, the form in which glucose is stored in muscle tissue and the liver; it stimulates the synthesis and storage of fats in fat depots and in the liver, and it inhibits the release of that fat. Insulin also stimulates the synthesis of proteins and of molecules involved in the function, repair, and growth of cel s, and even of RNA and DNA molecules, as wel .

Insulin, in short, is the one hormone that serves to coordinate and regulate everything having to do with the storage and use of nutrients and thus the maintenance of homeostasis and, in a word, life. It’s al these aspects of homeostatic regulatory systems—in particular, carbohydrate and fat metabolism, and kidney and liver functions—that are malfunctioning in the cluster of metabolic abnormalities associated with metabolic syndrome and with the chronic diseases of civilization. As metabolic syndrome implies, and as John Yudkin observed in 1986, both heart disease and diabetes are associated with a host of metabolic and hormonal abnormalities that go far beyond elevations in cholesterol levels and so, presumably, any possible effect of saturated fat in the diet.

This suggests another way to look at Peter Cleave’s saccharine-disease hypothesis, or what I’l cal , for simplicity, the carbohydrate hypothesis of chronic disease. As Cleave pointed out, species need time to adapt ful y to changes in their environment—whether shifts in climate, the appearance of new predators, or changes in food supply. The same is true of the internal environment of the human body—Bernard’s milieu intérieur. By far the most dramatic change to this internal environment over the past two mil ion years is due to the introduction of diets high in sugar and refined and other easily digestible carbohydrates. Blood-sugar levels rise dramatical y after these meals; insulin levels rise in response and become chronical y elevated—hyperinsulinemia—and tissues become resistant to insulin. And because half of every molecule of table sugar (technical y known as sucrose) is a molecule of the sugar known as fructose, which is found natural y only in smal concentrations in fruits and some root vegetables, the human body has also been confronted with having to adjust to radical y large amounts of fructose. In this sense, al of the abnormalities of metabolic syndrome and the accompanying chronic diseases of civilization can be viewed as the dysregulation of homeostasis caused by the repercussions throughout the body of the blood-sugar, insulin, and fructose-induced changes in regulatory systems. (As the geneticist James Neel wrote in 1998 about adult-onset diabetes, “The changing dietary patterns of Western civilization had compromised a complex homeostatic mechanism.”) It’s possible that obesity, diabetes, heart disease, hypertension, and the other associated diseases of civilization al have independent causes, as the conventional wisdom suggests, but that they serve as risk factors for each other, because once we get one of these diseases we become more susceptible to the others. It’s also possible that refined carbohydrates and sugar, in particular, create such profound disturbances in blood sugar and insulin that they lead to disturbances in mechanisms of homeostatic regulation and growth throughout the entire body.

Any assumptions about regulatory mechanisms and disease, as Claude Bernard explained, have to be understood in the context of the entire harmonic ensemble. “We real y must learn, then, that if we break up a living organism by isolating its different parts, it is only for the sake of ease in experimental analysis, and by no means in order to conceive them separately,” Bernard wrote. “Indeed when we wish to ascribe to a physiological quality its value and true significance, we must always refer it to this whole, and draw our final conclusion only in relation to its effects in the whole.” When Hans Krebs paraphrased this lesson a century later, he said that if we neglect “the wholeness of the organism—we may be led, even if we experimented skil ful y, to very false ideas and very erroneous deductions.”

Perhaps the simplest example of this kind of erroneous deduction is the common assumption that the cause of high blood pressure and hypertension is excess salt consumption.

Hypertension is defined technical y as a systolic blood pressure higher than 140 and a diastolic blood pressure higher than 90. It has been known since the 1920s, when physicians first started measuring blood pressure regularly in their patients, that hypertension is a major risk factor for both heart disease and stroke. It’s also a risk factor for obesity and diabetes, and the other way around—if we’re diabetic and/or obese, we’re more likely to have hypertension. If we’re hypertensive, we’re more likely to become diabetic and/or obese. For those who become diabetic, hypertension is said to account for up to 85 percent of the considerably increased risk of heart disease. Studies have also demonstrated that insulin levels are abnormal y elevated in hypertensives, and so hypertension, with or without obesity and/or diabetes, is now commonly referred to as an “insulin-resistant state.” (This is the implication of including hypertension among the cluster of abnormalities that constitute metabolic syndrome.) Hypertension is so common in the obese, and obesity so common among hypertensives, that textbooks wil often speculate that it’s overweight that causes hypertension to begin with. So, the higher the blood pressure, the higher the cholesterol and triglyceride levels, the greater the body weight, and the greater the risk of diabetes and heart disease.