The Misunderstood - or is it mischaracterized? - Pima

Alternate title:   Battle Pima ~ Bernstein v. Taubes

In the comments on a recent post, Galina linked me to some online material by Diabetes "guru" Dr. Richard Bernstein.   Anyone who's frequented low carb forums and blogs will recognize that name as probably the go-to authority on diabetes management with a low carb diet, and it's not too much of a stretch to state that he's the second-most cited authority behind the great Gary Taubes himself.    Significant portions of his book, The Diabetes Solution, are free to read online, including his chapter on Weight Loss.   He writes:

Before we discuss weight loss, it makes sense to consider obesity, because if you don’t understand why and how you are overweight or obese, it will be somewhat more difficult to reverse the condition.

THE THRIFTY GENOTYPE

When I see a very overweight person, I don’t think, “He ought to control his eating.” I think, “He has the thrifty genotype.” What is the thrifty genotype?

The hypothesis for the thrifty genotype was first proposed by the anthropologist James V. Neel in 1962 to explain the high incidence of obesity and type 2 diabetes among the Pima Indians of the southwestern United States. Evidence for a genetic determinant of obesity has increased over the years. Photographs of the Pimas from a century ago show a lean and wiry people. They did not know what obesity was and in fact had no word for it in their vocabulary. Their food supply diminished in the early part of the twentieth century, something that had occurred repeatedly throughout their history. Now, however, they weren’t faced with famine. The Bureau of Indian Affairs provided them with flour and corn, and an astonishing thing happened. These lean and wiry people developed an astronomical incidence of obesity—100 percent of adult Pima Indians today are grossly obese, with a staggering incidence of diabetes. Fully 65 percent of adults are type 2 diabetics. Since the publication of the first edition of this book, even many Pima children have become obese, type 2 diabetic teenagers. A similar scenario is now playing out across the United States in the general population. The pace may be slower, but the result is similar.

What happened to the Pimas? How did such apparently hardy and fit people become so grossly obese? Though their society was at least in part agrarian, they lived in the desert, where drought was frequent and harvests could easily fail. During periods of famine, those of their forebears whose bodies were not thrifty or capable of storing enough energy to survive without food died out. Those who survived were those who could survive long periods without food. How did they do it? Although it may be simplifying somewhat, the mechanism essentially works like this: Those who naturally craved carbohydrate and consumed it whenever it was available, even if they weren’t hungry, would have made more insulin and thereby stored more fat. Add to this the additional mechanism of the high insulin levels caused by inherited insulin resistance, and serum insulin levels would have become great enough to induce fat storage sufficient to enable them to live through famines. (See Figure 1-1.) Truly survival of the fittest— provided famines would continue.

So Bernstein endorses the Thrifty Gene hypothesis while Taubes argues against it (from GCBC):

The question of what causes obesity in these impoverished populations has typically been ignored by obesity researchers, other than to suggest that there is something unique about given groups of people that exacerbates the problem of obesity.  The assumption, as The New Yorker writer Malcolm Gladwell wrote about the Pima in 1998, is that they are “different only in degree, not in kind.”  

The idea of specific populations predisposed to obesity is encapsulated in a notion now known as the thrifty gene—technically, the thrifty-genotype hypothesis—that is now commonly invoked to explain the existence of the obesity epidemic and why we might all gain weight easily during periods of prosperity but have such difficulty losing it. The idea, initially proposed in 1962 by the University of Michigan geneticist James Neel, is that we are programmed by our genes to survive in the paleolithic hunter-gatherer era that encompassed the two million years of human evolution before the adoption of agriculture—a mode of life still lived by many isolated populations before extensive contact with Western societies. “Such genes would be advantageous under the conditions of unpredictably alternating feast and famine that characterized the traditional human lifestyle,” explained the UCLA anthropologist Jared Diamond in 2003, “but they would lead to obesity and diabetes in the modern world when the same individuals stop exercising, begin foraging for food only in supermarkets and consume three high-calorie meals day in, and day out.” In other words, the human body evolved to be what Kelly Brownell has called an “exquisitely efficient calorie conservation machine.” And so, by this hypothesis, we suck up calories when they are abundant and store them as fat until they are called upon in a time of need. “Your genes match nicely with a scarce food supply,” Brownell explains, “but not with modern living.” Such populations as the Pima and the descendants of African tribes, according to this logic, were until very recently still trapped in this cycle of feast and famine and scarce food in general, and so their thrifty genes have yet to evolve to deal with times of continual plenty. The NIH researchers who study the Pima, as Gladwell reported, “are trying to find these genes, on the theory that they may be the same genes that contribute to obesity in the rest of us.”

For the first few decades of its existence, this notion that we have evolved “thrifty mechanisms to defend energy stores during times of privation” was invariably referred to as a hypothesis. That qualification is now often dropped, but the thrifty gene remains only a hypothesis, and one that rests on many assumptions that seem unjustifiable.  

James Neel initially proposed the idea of a “thrifty genotype rendered detrimental by progress” to explain why diabetes was so prevalent in Western societies and yet apparently absent in primitive tribes, including the Yanomamo of the Brazilian rain forest, who were then the subject of Neel’s research.  Neel was addressing the diseases of civilization and the kind of observations that led Peter Cleave to propose his saccharine-disease hypothesis. (Neel was unaware of Cleave’s work at the time.) The enigma of Type 2 diabetes, Neel observed, is that it bestows significant evolutionary disadvantages upon anyone who has it. Diabetic women are more likely to die in childbirth and more likely to have stillbirths than healthy women; their children are more likely to be diabetic than those of healthy women. This implies that any genes that might predispose someone to become diabetic would evolve out of the population quickly, but this did not seem to have happened. One way to reconcile these observations is to imagine a scenario in which having a genetic predisposition to become diabetic is advantageous in some circumstances. (In a similar way, having the gene for sickle-cell anemia, normally a disadvantage, provides protection against malaria, a major advantage in malarial areas, as Neel himself reported.)  

Since diabetic mothers are known to give birth to heavier children, Neel speculated that these diabetic genes bestowed an exceptional ability to use food efficiently, and thus an exceptional ability to convert calories into fat. Those with such thrifty genes, Neel explained, “might have, during a period of starvation, an extra pound of adipose reserve” that would keep them alive when those who failed to fatten easily would die of starvation. So it would be beneficial to have such genes in the event of famine or prolonged food deprivation, which Neel now assumed must have been the case throughout our evolutionary history.  Those same genes would lead to obesity and diabetes in an environment in which food was plentiful.  

“If the considerable frequency of the disease is of relatively long duration in the history of our species,” Neel had asked to begin his discussion, “how can this be accounted for in the face of the obvious and strong genetic selection against the condition? If, on the other hand, this frequency is a relatively recent phenomenon, what changes in the environment are responsible for the increase?”  

The thrifty gene could be the answer only if diabetes was of long duration in the species—and there is no evidence of that. The disease seems to appear only after populations have access to sugar and other refined carbohydrates. In the Pima, diabetes appeared to be “a relatively recent phenomenon,” as Neel himself later noted. When Russell and Hrdli ka discussed the health of the Pima in the early 1900s, they made no mention of diabetes, even while noting the presence of such “rare” diseases as lupus, epilepsy, and elephantiasis.*71 As late as 1940, when Elliott Joslin reviewed the medical records of the hospitals and physicians in Arizona, he concluded that the prevalence of diabetes was no higher among the Pima and other local tribes than anywhere else in the United States. Only in the 1950s, in studies from the Bureau of Indian Affairs, was there compelling reason to believe that diabetes had become common. When Neel tested adolescent Yanomamo for the condition known as glucose intolerance, which might indicate a predisposition to diabetes, he found none, so had no reason to believe that diabetes existed before such isolated populations began eating Western foods. The same was true of an isolated tribe of Pima, discovered living in the Sierra Madre Mountains of northern Mexico. “The high frequency of [Type 2 diabetes] in reservation Amerindians,” Neel later explained, “must predominantly reflect lifestyle changes.”

By 1982, Neel had come to side with Peter Cleave in believing that the most likely explanation for the high rates of obesity and diabetes in populations like the Pima that had only recently become Westernized was their opportunity to “overindulge in high sugar content foods.”

So there you have it.  Were I to excerpt everything Taubes says about the thrifty gene, I'd probably run afoul of fair use law.  You can see a summary by Gatewing here.  Two "authorities", two different takes on the Thrifty Gene.  It is instructive to recognize that  Taubes bases a significant portion of his remaining TWICHOO on another Neel hypothesis as to the etiology of insulin resistance, and how IR causes obesity.  This is equally flawed vs. previous versions of his hypothesis, but the current working version whereby fructose is the real culprit.  I'll be addressing this soon.  Yep.  Taubes again. ;-)

In any case, Bernstein evokes the Pima as a model of famine induced genetic selection towards being more obesity prone.  While genetics doesn't seem to explain things, epigenetics does.  I apologize for not referencing this part, but there is a plethora of peer review literature on two phenomena that tend to explain the paradoxes we're told CICO does not.  There are some other explanations, but here's one.  Low birthweight for gestational age (and premature) babies are at high risk for obesity and diabetes later in life.  A period of famine would result in higher proportions of such babies born, and 20-30 years later, we see obesity and diabetes provided the famine has subsided.  If you do a Google Scholar search on famine and obesity or diabetes, the literature is full of this.  Even if born normal weight, malnutrition in childhood results in less weight gain, but the proportion of that weight that is squirreled away fat is far higher.  We see this in CR  studies conducted from birth -- the metabolic rate is downregulated and the organism becomes more efficient.  When the individual is adequately nourished later in life, they will more likely be in caloric surplus (due to suppressed metabolic rate) and be more likely to partition that surplus to adipose tissue.

Back to Battle Pima!  At right is a slide most will be familiar with from innumerable lectures.  Hey!  I just caught another inconsistency in GCBC ... say it ain't so!!!    Check out the graphic:  Fat Louisa is from 1901-1902!!!!!!   And yet I repeat from above:

When Russell and Hrdlika discussed the health of the Pima in the early 1900s, they made no mention of diabetes.

Now Louisa is just the poster woman for obesity, but since we're talking thrifty genes and all that, not to mention Neel's {paraphrase} "anything that raises insulin causes insulin resistance"  hypothesis, this crack in the timeline is pretty substantial here.  So nevermind that Bernstein is sunk by the prosperity of the Pima in the mid 1800's, Gary's pretty sunk using Louisa (who perhaps was the Pima equivalent of the Fat Lady at the circus rather than representative of the population?!).

But what do Taubes and Bernstein share in common?  An ignorance of facts I would contend.  It's not like the literature is not full of studies on the Pima.  One that I've cited repeatedly is Boyce & Swinburn's 1993 analysis of the Pima diet circa turn of the 20th century:  "although seasonably variable, was ∼ 70–80% carbohydrate, 8–12% fat, and 12–18% protein" .  Another study (Ravussin et.al.) compared the Arizona Pima to Mexican Pima in 1994. 

The Pima diet consumed at the time of the study (October) appeared very monotonous and lacked several essential nutrients because of the relative absence of fruits and vegetables. The main staples were beans (Phaseolus Vulgaris in four varieties), corn as tortillas, and potatoes.  Preliminary data by semiquantitative food frequency and 24-h recall suggests that ~23% of total energy intake is derived from fat. This amount seems to be slightly higher than that reported in the diet of the Tarahumara Indians (41) but much lower than that in the present Arizona Pima diet (32). The main sources of protein and carbohydrate in the diet were corn tortillas, wheat flour tortillas (which include ~30% vegetable fat in their formulation), and beans, which are typically fried with variable amounts of vegetable oil or shortening (Table 2). Other important energy sources were inexpensive pasta soups and potatoes, which are cultivated in the region or sold by traveling vendors. The consumption of animal products, such as meat and poultry, was rare, and, in most cases, these items were consumed only once every month or two. However, eggs and powdered milk were more frequently used, depending on the availability of cash to purchase such items. Dietary fiber intake was probably high (>50 g) because of the substantial consumption of beans and tortillas.

Sorry, but this sorta puts the whole low fat and even NAD angle seriously in question, wouldn't you say?  Veggie oils, grains, legumes and a relative absence of animal fats and proteins in Mexico with substantially lower incidence of obesity and diabetes.  At 23% fat, modern Mexican Pima are consuming more than Arizona Pima circa 1900.    Is carbohydrate causing the problems for the Pima we see today?  I don't see how anyone can make that claim with a straight face.  The conflicting use of the Pima by Taubes and Bernstein brings the credibility of both into question.