Industry Figure Tom Chappell

(Back to Parts One, Two, Three, Four, Five, Six, or Seven)

By the 1990’s, researchers started reporting that heart disease and Alzheimer’s seemed to share risk factors: hypertension, atherosclerosis, and smoking were all associated with an increased risk of Alzheimer’s disease.

The connection with insulin and high blood sugar is concrete: “Type 2 diabetics have roughly twice as much risk of contracting Alzheimer’s disease as nondiabetics. Diabetics on insulin therapy…[have] a fourfold increase in risk. Hyperinsulinemia and metabolic syndrome are also associated with an increased risk of Alzheimer’s disease.”

In part, this is due to vascular damage, which is more common in diabetics — and vascular damage in the brain is a well-known cause of dementia.

But vascular dementia aside, there are two other lines of evidence linking high blood sugar and/or high insulin levels to Alzheimer’s disease proper:

1. When blood sugar levels are high, the excess sugars are more likely to semi-randomly bind with proteins — the sugar molecules are sticky, in a chemical way, to protein molecules. In fact, they’re so sticky that a protein might end up folded over and attached in more than one place to a sugar molecule, or multiple proteins may glom together with one or more sugar molecules into a big untidy mess.

   These glycated (”sugar-frosted”) proteins can end up as twisted, gnarled Advanced Glycation End-products (”AGEs”), which can overwhelm and confound our bodies’ clean-up crews. Plus, they’re a source of oxidative stress, generating free radicals. Bad news all around.

   Now, organic chemicals depend on their shape as much as their chemical formula for their actions: Our bodies, for example, can only use so-called right-handed sugar; the chemically-identical, but physically mirror-imaged left-handed sugar is indigestible. As another example, Mad Cow disease is caused by a perfectly-normal protein being folded into an abnormal shape, which “infects” other proteins by encouraging them to take on this same dysfunctional and highly-stable shape. Not only are the proteins wrong, they like being wrong, and are good at persuading other proteins to join their evil gang.

   But I digress. The main point here is that your body’s workhorse chemicals can get an unwelcome sugar coating that is difficult to remove. In fact, one of the better tests for diabetes and insulin resistance is the A1c, which measures the percentage of your hemoglobin that has become sugar-frosted. Mine is 5.2%. We like it to be below 6.0%. Diabetics are happy to get it down to 7.0%. Unlike the fasting blood glucose test, which measures blood sugar levels due to what you’ve been doing in the last few hours, the A1c measures your average blood sugar level over the last two to three months. And the reason it can do that is because once your hemoglobin has been glycated, it tends to stay that way.

   When this process happens to brain proteins, the results aren’t pretty:

Investigators studying AGEs have proposed that Alzheimer’s starts with glycation — the haphazard binding of reactive blood sugars to…brain proteins. Because the sugars stick randomly to the fine filaments of the proteins, this in turn causes the proteins to stick to themselves and to other proteins. This impairs their function and, at least occasionally, leaves them impervious to the usual disposal mechanisms, causing them to accumulate in the spaces between neurons. There they cross-link with other nearby proteins, and eventually become advanced glycation end-products. All of this would then be exacerbated by the fact that the glycation process itself generates more and more toxic reactive oxygen species (free radicals), which in turn causes even more damage to the neurons. In theory, this is what causes the amyloid plaques and leads to the degeneration of neurons, the cell loss, and the dementia of Alzheimer’s. The theory is controversial, but the identification of AGEs in the plaques and tangles of Alzheimer’s is not.

…from Good Calories, Bad Calories (Knopf, 2007), by Gary Taubes, p. 206

2. And what about high insulin levels? Sure, they’re implicated as well. Imagine, for a moment, that you’re a pancreas. Your host eats a sugary meal, extremely delicious, but blood glucose levels are rising, and must be suppressed. Quick, a shot of insulin! Perfect, the glucose levels go down (or don’t, depending on how insulin-resistant the host is).

   But consider: we need some mechanism to bring insulin levels back down to normal after the pancreas stops spewing it out into the bloodstream. And it turns out that there’s an enzyme, IDE (insulin degrading enzyme) that really likes to tear down insulin.

   Seems like a good system, but IDE has a second job, a side job, that it agreed to do in its spare time if there wasn’t much super-important insulin to tear down. Wanna guess? Yes, that’s right: tearing down the amyloid plaques that clutter the brains of Alheimer’s patients:

The more insulin available in the brain, by this scenario, the less IDE is available to clean up amyloid, which then accumulates excessively and clumps into plaques. In animal experiments, the less IDE available, the greater the concentration of amyloid in the brain. Mice that lack the gene to produce IDE develop versions of both Alzheimer’s disease and Type 2 diabetes…

In 2003, [Suzanne Craft, a neuropsychiatrist at the University of Washington], reported that when insulin was infused into the veins of elderly volunteers, the amount of amyloid in their cerebral spinal fluid increased proportionately. This implied that the level of amyloid protein in their brain had increased as well. The older the patient, the greater the increase in amyloid protein. As Craft sees it, if insulin levels are chronically elevated (hyperinsulinemia), then brain neurons will be excessively stimulated to produce amyloid proteins, and IDE will be preoccupied with removing the insulin, so that less will be available to clean up the amyloid…

This isn’t to say that eating carbohydrate foods to excess is a [proven] cause of Alzheimer’s, only that mechanisms have now been identified to make the hypothesis plausible.

…from Good Calories, Bad Calories (Knopf, 2007), by Gary Taubes, p. 208

Continued in Part Nine…