Sunday, March 1, 2015

Carbohydrates, Linoleic Acid (Omega-6 Fat), and Disease

From some comments on another forum:
I agree that obesity alone ought to be considered a symptom of a disease. Wrt [Metabolic Syndrome], I don’t know that the problem is so much the wearing out of the pancreas as it is increasing cellular resistance to insulin, but that’s probably nitpicking. As you say, it’s insidious.
There appear to be two basic causes of diabetes.  Auto-immune (type I) and rejection of glucose as a fuel source (type II).  Some people have a spectrum of both, which gives rise to the appearance of the pancreas “getting tired”.

John’s explanation is the standard Dr. explanation for type II, but I think it’s wrong.

What appears to happen is that constantly running your body on glucose causes damage to the mitochondria, and if they don’t get a break, they get more and more damaged via oxidation, which leads to many of the other symptoms of Metabolic Syndrome, like Alzheimer's’ (aka Type III diabetes), heart disease (fibrosis, specifically), and cancers.  Eventually cells become insulin resistant because they’re attempting to stop the damage that comes from continually running on glucose: they’re rejecting the fuel.  One of the characteristics of type II diabetes is high, not low, insulin levels.  The body is desperately trying to rid itself of excess glucose, and the cells are refusing to use it. (Metformin, one of the most effective treatments for type II diabetes, alters mitochondrial function, forcing the cells to burn glucose.)

The other required ingredient is a diet high in omega-6 fats.  These alter the function of many parts of the body, but specifically they make the mitochondria produce more oxidative damage when running on glucose, and they themselves get oxidized, damaging the rest of the body, as they’re toxic when oxidized.

Avoiding the metabolic syndrome seems to be as simple as not running your body on glucose 24/7.  In mice, simply forcing them to fast 16 hours a day prevents the syndrome, even if you’re feeding them exactly the same type and quantity of food.
…If I were a Progressive who has adopted a paleo viewpoint on diet, I think I’d challenge your assumption that all this comes from Progressives, though.
No, it doesn’t all come from the Progressives.  Using government to improve agriculture does, though, and advocating a specific, harmful dietary pattern does.  Those two factors are what has lead to a 70% overweight rate in the US.

They deserved to be blamed for it.  They deserve a lot worse…

“What we discovered is that all of these different pathogenic mechanisms do reflect a single hyperglycemia-induced process and that this single unifying process is the overproduction of superoxide by the mitochondrial electron transport chain.”

The Pathobiology of Diabetic Complications

Fascinating paper.

Ending hyperglycemia is, of course, the easiest thing in the world: stop eating carbohydrates in excess of your body’s capacity to process them.  If you do so, virtually all the symptoms of the metabolic syndrome are reversible.

And for the omega-6 part:
“Alterations in cardiolipin structure, content and acyl chains composition have been associated with mitochondrial dysfunction in multiple tissues in several physiopathological conditions, including ischemia/reperfusion, different thyroid states, diabetes, aging and heart failure. Cardiolipin is particularly susceptible to ROS attack due to its high content of unsaturated fatty acids. Oxidative damage to cardiolipin would negatively impact the biochemical function of the mitochondrial membranes altering membrane fluidity, ion permeability, structure and function of components of the mitochondrial electron transport chain, resulting in reduced mitochondrial oxidative phosphorylation efficiency and apoptosis. Diseases in which mitochondrial dysfunction has been linked to cardiolipin peroxidation are described.”

Role of cardiolipin peroxidation and Ca2+ in mitochondrial dysfunction and disease

Omega-6 consumption drives cardiolipin polyunsaturate concentrate:

The level of linoleic acid in neural cardiolipin is linearly correlated to the amount of essential fatty acids in the diet of the weanling rat

The same thing's been shown for multiple human tissues.