Gerald Reaven is the researcher who first identified the state of insulin resistance and played a central role in defining its consequences. Understanding insulin resistance is worthwhile, and if we want to do so, his work is one of the most informative places to look. I recently read his general-audience book Syndrome X: The Silent Killer, and I’ll share my thoughts on it in this review.
While doing research for my review of The Case Against Sugar, I saw that Gerald Reaven had written a general-audience book on insulin resistance, its consequences, and how to manage it. The book is titled Syndrome X: The Silent Killer, and it has two co-authors named Terry Kristen Strom and Barry Fox. It was published in 2000 and is a bit outdated in some ways, but since Reaven has played such a key role in our modern understanding of insulin resistance, much of the information it contains is still relevant. It isn’t very technical but it does cover a lot of scientific ground, and the book includes a nice bibliography at the end chronologically summarizing Reaven’s work on this topic as of 1999.
My review will be organized differently than the book, but in the way that I find the most logical. First, I’ll discuss Reaven’s definition of insulin resistance and a related condition he calls “syndrome X”, then what causes it, then its consequences, and finally how to manage it.
What is syndrome X?
Syndrome X is Reaven’s term for a common cluster of metabolic abnormalities that is now more commonly called the metabolic syndrome. This includes some combination of elevated circulating insulin, high blood pressure, high blood triglycerides, low HDL cholesterol, slow clearance of glucose and fat from the blood following a meal, small, dense LDL particles, increased blood clotting, and a decreased ability to dissolve blood clots. Today, abdominal obesity is also considered a defining characteristic. The book says that syndrome X affects 25-30 percent of people, although the number is likely higher today.
The common cause of these metabolic problems, the authors argue, is an impaired response of tissues to the hormone insulin. Insulin is a very important hormone for metabolic regulation. It plays many roles, but most of them revolve around regulating levels of glucose and fat in the blood, and coordinating the metabolic shift between using carbohydrate vs. fat as fuel in response to what’s coming in via the diet.
When tissues don’t respond to insulin effectively, the pancreas secretes more of it in an attempt to compensate. Yet different tissues become insulin resistant to different degrees, so in the end some tissues get too little insulin while others get too much. This, they argue, likely accounts for the various manifestations of syndrome X.
The causes of syndrome X
The book’s position on the causes of insulin resistance and syndrome X is inconsistent, at least superficially. The authors repeatedly state that excess body fatness, physical inactivity, cigarette smoking, and genetics contribute to insulin resistance, and that weight loss and exercise can substantially decrease insulin resistance. Yet in chapter 6, one of the “fallacies” they list is that obesity causes insulin resistance.
How do we reconcile this apparent contradiction? I think the point the authors were trying to make with their “fallacy” comment is that obesity is not the sole driver of insulin resistance, and that genetics may in fact be more important. Elsewhere in the book, they explore the evidence on the contributions of genetics, body fatness, and lifestyle to insulin resistance, and conclude that genetics accounts for about half of it, body fatness about 25 percent, and physical fitness about 25 percent. This is consistent with the current majority view in the scientific community, which I share, that insulin resistance is primarily driven by body fatness, physical inactivity, and genetics.
Reaven has harsh words for public low-carbohydrate diet advocates such as Robert Atkins, who he feels have misrepresented his research. I don’t know what Atkins wrote about Reaven’s work, but it was definitely misrepresented in Gary Taubes’s book The Case Against Sugar. Reaven’s work validates some of the views that are prevalent in the low-carbohydrate diet community and undermines others. It’s notable that nowhere in the book do they argue that eating carbohydrate or sugar contributes to insulin resistance, and they also state that calorie intake and expenditure, not macronutrients, determine body fatness.
The consequences of syndrome X
Much of Reaven’s research, and his book, focused on the cardiovascular consequences of syndrome X. From the list of metabolic characteristics I shared above, it’s not hard to understand how syndrome X might damage the cardiovascular system. High blood pressure, high blood glucose and lipids, low HDL, high triglycerides, small, dense LDL particles, and a tendency to form blood clots are all risk factors for cardiovascular disease. Consistent with this, his research has shown that insulin resistance is a strong predictor of cardiovascular risk (1).
He also discusses how syndrome X often gives way to type 2 diabetes as the pancreas fails to keep up with the increasing insulin demands of insulin-resistant tissues. Reaven’s subsequent work provided a compelling basis for believing that insulin resistance is a major driver of chronic disease, including coronary heart disease, diabetes, and perhaps even cancer (2).
In popular discussions of cardiovascular disease risk, I often see two opposing camps. One camp thinks cardiovascular disease is all about LDL cholesterol, and insulin resistance is unimportant. The other camp thinks insulin resistance is everything, and LDL cholesterol is unimportant. In Syndrome X, the authors take a position that I think remains the most evidence-based today: LDL and insulin resistance are both important drivers of cardiovascular disease risk. They argue that the absence of elevated LDL cholesterol is not sufficient assurance of low cardiovascular risk, and that LDL cholesterol and insulin resistance are largely independent of one another and must be managed separately.
Managing syndrome X
The authors state that people with syndrome X respond poorly to high-carbohydrate, low-fat diets because these diets accentuate the excessive insulin release that underlies some of the metabolic features of the syndrome. While a person who is insulin sensitive may thrive on such a diet, someone who is insulin resistant may not. This is important because in the late 1990s when the book was written (and to some extent today), this was precisely the type of diet that was prescribed for people with obesity, cardiovascular disease, and prediabetes.
As an alternative, the authors offer the “Syndrome X Diet”. In a nutshell, this is a diet in which carbohydrate is partially replaced by unsaturated fat. The book contains extensive meal plans illustrating how to apply the diet. Looking through the meal plans, much of the fat comes from low-trans-fat margarine. My view is that it would be preferable to get unsaturated fat from whole food sources like nuts, avocados, and poultry.
This portion of the book contains a few statements that had me scratching my head. For example, poultry fat is classified as “saturated”, although it is generally about one quarter saturated or less. Because of this, they recommend low-fat cuts such as skinless breast. It seems to me that if the goal is to eat more unsaturated fat and less carbohydrate, full-fat poultry should be helpful.
It’s important to point out that the Syndrome X Diet is not really a low-carbohydrate diet, although my impression from the book is that Reaven isn’t against low-carbohydrate diets as a therapeutic tool. Here is the recommended macronutrient breakdown of the Syndrome X Diet, by calories:
- 45 percent carbohydrate
- 40 percent fat
- 15 percent protein
It’s worth noting that these numbers are pretty close to what the average American was eating in the year the book was published, as reported by the USDA (these add up to 101% due to rounding error; 3):
- 48 percent carbohydrate
- 41 percent fat
- 12 percent protein
So I think the goal of the Syndrome X Diet is not so much to eat a low-carbohydrate diet, but to avoid a low-fat diet.
In addition to diet, the authors recommend weight loss and physical activity to improve insulin sensitivity. As they note, these two approaches have been repeatedly shown to reduce insulin resistance.
Syndrome X is a classic book written by a giant in the field of physiology, and I think it has stood the test of time relatively well. Although some of Reaven’s views were controversial at the time he first articulated them, at this point many of them have been incorporated into mainstream thinking.
Syndrome X probably won’t satisfy researchers who want a more technical view of Reaven’s work, but it does review this research in a way that’s approachable for a general audience, and offers evidence-based strategies for managing insulin resistance.