I was reading the reviews of Gary Taubes' new book Good Calories, Bad Calories on the Amazon.com website and was amused to see that for the most part the reviewers gave him either 1 Star or 5 Stars.  He was either loved or hated.  There must be many good reasons for such a polarized reception to what he had to say but my impression was that the line in the sand was drawn based on his discussion of the "fat vs carbohydrate" hypothesis.

Much of the literature studying the impact of various subcategories of macronutrients (such as saturated fat, trans fat, starch, and rapidly absorbed or refined carbohydrates) on vascular disease has been limited by the tools available for evaluating their propensity to modulate specific lipid parameters or other biological endpoints.  Variances in these variables are then related to heart attack rates, strokes, Alzheimer's disease or other cardiovascular endpoints.  As technology advances, the tools become available to more intimately dissect and measure physiologic indicators that will ultimately be found to reliably predict desired clinical outcomes of interest.  Until appropriate tools are available, scientists must often rely on inadequate metabolic measurements and opine about their prognostic implications.

In his review of the science behind the 'fat' hypothesis of heart disease, Mr. Taubes starts with the parameter of choice at the time, that being TC (Total Cholesterol).  He describes how it was quantitated in thousands of persons in numerous large studies designed to prove that TC was a predictor of future heart disease in broad population groups (as opposed to those subjects with familial hyperlipidemia).  Since the distribution of TC was almost superimposable between the groups with and without heart disease, it clearly was a poor discriminator between the two.

Following TC as the preferred indicator was LDL cholesterol (a. k. a.-the 'bad' cholesterol).  This was a bit better.  The latest, and hopefully most discriminating parameter thus far is the subclass determination of LDL cholesterol as measured by gradient gel electrophoresis.  This is a blood test that identifies the component particles that are the purported 'bad actors' in the heart disease saga-the small, dense LDL particles located in subfraction IVb.  Levels above 10% appear to identify those individuals who are at greatest risk of undergoing invasive cardiac surgeries such as angioplasty, stenting, and bypass procedures. 

This parameter is directly related to serum triglyceride levels and inversely related to HDL cholesterol (the 'good' cholesterol) levels.  The small, dense LDL particles are those that studies have shown are the most likely to damage blood vessels.  Because they vary as the HDL and TG levels do, they are intimately related to the action of insulin and insulin and blood sugar levels.  They are also linked to inflammatory mediators such as CRP (C-reactive protein), an indicator of inflammation throughout the body and a well-established predictor of future cardiac events.

Hopefully as measurement of LDL subclasses become more commonplace, discourses on heart disease will become less divisive.

Alzheimer's disease is a chronic disease frequently associated with age.  It is the most common dementing illness and affects 50% of those who reach age 85. Type II diabetes, insulin resistance and the Metabolic Syndrome are all considered risk factors for this disorder because they double or triple the chances of developing it and may also accelerate disease progression.  Based on this observation, it is reasonable to conclude that abnormalities of either blood sugar or insulin metabolism play a pivotal role.  If that is true, then it is likely that refined and other rapidly digested carbohydrates are important factors as well.

The characteristic brain tissue findings associated with Alzheimer's disease, senile plaques and neurofibrillary tangles , were identified by Alois Alzheimer about 100 years ago.  The 1990s were called the "Decade of the Brain" and with this designation research on Alzheimer's disease was put in the cross hairs of neurological investigators.  While this helped, what really was instrumental in facilitating an improved understanding of what caused the disease was the recognition that aberrations of glucose and insulin metabolism were associated with increased incidence. 

Among the vanguard of scientists pursuing this approach is Dr. Suzanne Craft at the University of Washington.  She has documented numerous abnormalities of glucose and insulin metabolism in Alzheimer's disease and has observed associations between these metabolic changes and the physiology of the beta-amyloid peptide found in the senile plaques that accumulate in the brains of afflicted patients.  Additional investigators pursuing this lead have found aberrations in the insulin signaling pathway in the brain,  while other neuroscientists have identified a link between the degradation of beta-amyloid and IDE (Insulin Degrading Enzyme-the enzyme responsible for recycling the hormone insulin).  When researchers inject a compound into the brains of mice that blocks the insulin receptor in the brain, or separately blocks the insulin signaling pathway, the animals develop plaque-like deposits and become demented.  Doctors from Brown University Medical School have coined the phrase "Type III Diabetes" to refer to the inability of the brain to properly use glucose in Alzheimer patients, akin to what happens in the bodies of diabetics.

To evaluate whether such findings have clinical merit, Dr. Craft conducted a study in patients suffering from Alzheimer's disease.  There are pharmaceutical compounds on the market that are able to improve the body's sensitivity to insulin.  She asked the question, if insulin resistance (the metabolic abnormality linked with diabetes and the Metabolic Syndrome) truly does play a seminal role in this form of dementia, then a drug that is able to improve insulin sensitivity should be a beneficial treatment.   That is exactly what she found!  Such observations serve to open the door for new pharmaceutical approaches.

The most exciting news is that factors other than drugs can improve insulin sensitivity.  They are diet and lifestyle choices including good nutrition, weight maintenance and exercise-all easily within our purview.  The new book Good Calories, Bad Calories by Gary Taubes provides novel nutritional recommendations to help in this regard. 

Just remember, the time to get started on such a brain-healthy program is now.