Book Review: Syndrome X, The Silent Killer

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  It was published in 2000 and is a bit outdated in some ways, but since Reaven has played such a key role in our modern understanding of insulin resistance, much of the information it contains is still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.

The verdict

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.

15 Responses to Book Review: Syndrome X, The Silent Killer

  1. “Magnesium is an essential mineral that many people apparently don’t get enough of. One of the many things it’s necessary for in mammals is proper insulin sensitivity and glucose control.”

    “In insulin resistant volunteers with low blood magnesium, magnesium supplementation for four months reduced estimated insulin resistance by 43 percent and decreased fasting insulin by 32 percent (13). This suggests to me that magnesium deficiency was probably one of the main reasons they were insulin resistant in the first place.”

    “I believe that an adequate magnesium intake is critical for proper insulin sensitivity and overall health.”

    Who wrote those things? One Stephan Guyenet, 7 years ago. Now you think insulin resistance is due to body fatness, physical inactivity, and genetics. Not Mg deficiency, apparently.

    • Hi Jane,

      Still just as ornery as ever, I see.

      Many things contribute to insulin sensitivity and I didn’t say that body fatness and physical activity are the only factors. They are likely the main factors in the general population though. Insufficient Mg could play a role as well. But if insulin resistance were simply a matter of Mg deficiency, we’d know about it, people would be taking supplements, and no one would be insulin resistant.

      • Of course insulin resistance is not simply a matter of Mg deficiency. Other micronutrients are removed from refined carbs as well, and some of them are just as important in energy metabolism as Mg is.

        If you want to say body fatness and Mg deficiency are causes of insulin resistance, you have to consider the possibility that Mg deficiency is a cause of body fatness. But you don’t.

  2. Good day Stephan. Best wishes with the launch of your new book – I will be buying this once it is published in the UK. I should also add that one of your articles – on the old site I think – is still my anchor point when I think about or refer to the predominant models of obesity. With that I have a question: you clearly identify the mind-gut axis (my words) as a key part of the problem. However, I haven’t see you refer to the microbiome, not that I have read everything you have written – clearly!

    Given the huge strides in understanding in this area do you, even though you don’t appear to have a specialism in microbiology, think (or allow) that this “organ” may play a role in the obesity riddle? Many thanks for your consideration. Kind regards, Tom

    • Hi Tom,

      It may well play a role. Gut-brain communication is important for body weight regulation, and the microbiome impacts that. But it remains unclear how much of an impact this has in humans. There is suggestive evidence but we don’t have a smoking gun yet.

  3. Hey Stephan:

    In your book which I blew through in four sittings over 2 days, I seem to get the impression that you are at least considering the possibility that higher intakes of protein might be key.

    Is that a correct impression?

    I’ve been dabbling with higher protein lately, about 30%, trading off carb and fat willy nilly as preferred, usually a few days at a time alternating. The higher protein seems to be so uniquely satiating that I wonder if the fat vs. carb war is rather pointless in that paradigm. This is in the context of mostly whole, “frugal” food.

    • Hi Richard,

      I do think protein has a major impact on satiety and possibly the setpoint. I think this controlled feeding study was the most striking demonstration of the effect:

      In the book, I argue that higher protein may actually be an “active ingredient” in low-carb diets, rather than lower carbohydrate itself– at least for moderate LC (as opposed to ketogenic diets). I don’t think the evidence is definitive, but it is suggestive. And yes, I do think that goes some way toward undermining the fat vs. carb war. Still, I recognize the possibility that people may respond differently to fat or carb such that they don’t respond in an “average” way.

      I also think that diets at the extremes of macro composition, such as very-low-carb and very-low-fat (e.g., McDougall), may have certain advantages for metabolism and weight control that are not seen in more moderate versions.

      • Hi Stephan:

        Oh, that’s comforting that I seem to have gotten the correct impressions. I’m not quite sure of all of what’s going on, but I’m seeing gentle movement in what I consider a good direction.

        Up to you whether to put this through, but I wrote a post about a recent presentation given by David Ludwig that Mike Eades blogged about, and it’s not your average insulin hypothesis deal. He even talks of palatability and looks to me like he’s thinking in the right direction in making distinctions between different forms of carbohydrate (as is done in Paleo/LC circles concerning meat and fat already).

        Anyway, I thought this little comment exchange was apropos. Hope you don’t mind. Hope the book endeavor is going well.

  4. I think you know that the production of HNE from Linoleic acid appears to be a cause of insulin resistance.

    Why no mention?

    You documented the increase in consumption earlier with nice graphs – we really didn’t eat much concentrated veg oil until 1960.

    <a href="; Lipid Peroxidation by-Products and the Metabolic Syndrome

  5. “I argue that higher protein may actually be an “active ingredient” in low-carb diets”

    It may also be the “active ingredient” in bodybuilder’s diets derived empirically from decades of trial and error in pursuit of radical body recomposition. Granted that in that population other factors (steroids, GH, etc.) play a major role, but the naturals use very high protein as well, and the results speak for themselves.

    Related, an anecdote: the very first nutrition book I ever read, back in the 70s, was Adelle Davis, “Let’s Get Well”. In that book, IIRC, she spoke of her approach to obesity. She instructed her would-be weight-losers to forget about restricting things, and just focus on protein, with a target of 200 grams per day. Within a few days, they all complained that they could not eat that much food, and soon after they were happily dropping weight. I’ve employed this technique myself several times and it does indeed work. The protein is highly satiating and crowds-out everything else. Combine this with high fiber intake — powdered psyllium, in addition to fibrous foods — and you have a recipe for satiety at quite modest calorie intake, and almost no room at all for your favorite fattening garbage.

    • The high protein concept is similar to Cordain’s Paleo Diet too. Ad libitum lean meat, non-starchy vegetables and fruit. It’s satisfying and functions well for weight loss every time. For me it’s hard to keep at it for long periods, though my brother-in-law does and swears by it.

    • and yet low carbers eat less proteins (by percentage) than the average american, usually staying between 10 and 20 percent. I do think high fiber is (one of the) key, but that is code for “eat potatoes and beans, not grains and sugar”, no? Plus it introduces a correlation in that cellular carbohydrates, magnesium, potassium, and fiber are all in the same food.

  6. “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.”


    I think you have forgotten a third group. Those that believe insulin resistance and LDL are not independant variables. The lipid panels of insulin resistant individuals appears vastly different than those without the disease. The presence of insulin resistance has dramatic effects on lipid parameters, particularly LDL particle number. Insulin resistance also has dramatic effects on cholesterol efflux and HDL particle number as well.