Saturday, February 23, 2013

Thyroid Hormone, Desaturase Enzymes, and the Implications on Membranes and Energy Generation

Purely based on physical and chemical considerations, it’s becoming clear that higher   membrane saturation indices go hand in hand with longevity and a greater resistance to toxic substances like lipopolysaccharide.

The types of saturated fats and unsaturated fats, as well as the proportion of each in the cellular membranes, are governed largely by the types of fats ingested and the body’s nutritional status and hormonal milieu.  It’s been touched on previously on this blog but insulin, for instance, activates several desaturase enzymes, which explains why fats synthesized from carbohydrates, via DNL, consist of a mixture of saturated & monounsaturated fats.

(On the other hand, food restriction tends to increase the saturation indices of membranes, and not simply because food-restricted individuals are incidentally ingesting less unsaturated fats, as I’ve recently heard suggested off hand.)

These inherent processes, whereby saturated fats are converted to unsaturated fats, seem to be important for controlling the fluidity of cellular membranes so that enzymes, such as lipases, which only operate within a range of membrane viscosities, can act on cellular lipids.  Oxygen and the reducing equivalents, NADH & NADPH, are essential cofactors of the desaturase enzymes. (Fructose depletes NADH.)

Thyroid supplement users should take note of the fact that thyroid hormone tends to decrease the saturation indices of membranes.

Friday, February 15, 2013

The Half-Life of Human Fat Tissue is 600 Days?



In the 1940s, some of the toxic effects of fish oil (such as testicular degeneration, softening of the brain, muscle damage, and spontaneous cancer) were found to result from an induced vitamin E deficiency. Unfortunately, there isn't much reason to think that just supplementing vitamin E will provide general protection against the unsaturated fats. The half-life of fats in human adipose tissue is about 600 days, meaning that significant amounts of previously consumed oils will still be present up to four years after they have been removed from the diet.  - Dr. Ray Peat


If there was ever an adage passed around by Dr. Peat’s followers that’s left my head spinning, it’s this one.  Several people have so far asked me to comment on it so here we go.

Bear in mind that triglycerides are continuously being broken down into their component fatty acids and glycerol by the enzyme hormone-sensitive lipase (HSL), which is inhibited by insulin and activated by noradrenalin.  Some degree of lipolysis and reesterification is happening all the time.  This is called the triglyceride-fatty acid cycle.2

Dr. Peat says that the half-life of fat in the adipose tissue is 600 days.  The half-life is the time it takes for the concentration of a substance to decrease by half.  So after 1 half-life, the concentration would have fallen to one-half of the original concentration; after 2 half-lives, the concentration would have fallen to one-quarter of the original concentration; after 3 half-lives, the concentration would have fallen to one-eighth of the original concentration; and so forth.

The half-life quoted by Dr. Peat was not explained in the study referenced by him, and so I followed the breadcrumbs to a paper by Hirsch and colleagues, which was luckily available (Hirsch, Farquhar, Ahrens, Peterson, & Stoffel, 1960).

Thursday, February 14, 2013

Insulin's Role in Blood Glucose Regulation




"Insulin is important in the regulation of blood sugar, but its importance has been exaggerated because of the diabetes/insulin industry. Insulin itself has been found to account for only about 8% of the "insulin-like activity" of the blood, with potassium being probably the largest factor. There probably isn't any process in the body that doesn't potentially affect blood sugar.


When I initially read this quotation posted by one of Dr. Peat’s ardent followers on Facebook, it caught my attention because I was under the impression that insulin was the dominant factor in regulating blood glucose levels.

Normally, when blood levels increase, the beta-cells of the pancreatic islets secrete insulin into the bloodstream, where it binds to insulin receptors on organs and tissues throughout the body.  The adipose tissue, liver, and muscles are the principle sites that insulin exerts its actions on.  In effect, insulin is a storage hormone that rapidly clears nutrients out of the bloodstream.

(1) In the fat tissue, insulin suppresses the mobilization of fatty acids and promotes the synthesis of fatty acids and triglycerides.
(2) In the liver, insulin inhibits gluconeogenesis and glycogen breakdown and stimulates glucose oxidation and glycogen synthesis.
(3) In the muscles, insulin stimulates amino acid uptake and protein synthesis.

According to some of the most widely read physiology textbooks, in the absence of insulin all of the above processes become impaired, and fatty acids and amino acids are released in large amounts into the bloodstream from the fat tissue and muscles, respectively.  In the liver, these fatty acids are used to generate ketone bodies and the amino acids, substrates for gluconeogenesis, are used to generate glucose.  Because fatty acids flow to the liver at a high rate, and because insulin normally stimulates the use of ketone bodies by cells in the body, ketone bodies—namely acetone—accumulate in the bloodstream, thereby leading to acidosis, coma, and death.

Friday, February 8, 2013

Quick commentary on Dr. Lustig’s take on fructose




I’ve recently had the opportunity to skim through Dr. Robert Lustig’s book, Fat Chance.  I haven’t watched his YouTube lecture (and I don’t plan to), which people have used to justify the avoidance of fructose (and sugar) on, but I’m assuming that the main arguments in the lecture are summarized in his book.    I’m planning on addressing the entire book, bit by bit, but first, herein, I will provide commentary on each of Dr. Lustig’s conclusions about fructose, which can be found on pages 120 to 121.  Dr. Lustig’s comments are in red.


1. Triple the dose mean the liver needs triple the energy to metabolize this combo versus glucose alone, depleting the liver cell of adenosine triphosphate (or ATP, the vital chemical that conveys energy within cells).  ATP depletion leads to the generation of the waste product uric acid.  Uric acid causes gout and increases blood pressure.

This supposition was addressed briefly here.  

In short, there is no evidence that fructose, in the way that it’s consumed in the US now (i.e., with glucose), increases blood uric acid levels or causes gout.

Large doses of liquid fructose, unreflective of the consumption habits of the majority of the US population, does, in fact, raise uric acid levels, but this rise is only transient, no where near the levels seen in gout, and not necessarily harmful.


2. The fructose does not go to glycogen.  It goes straight to the mitochondria.  Excess acetyl-CoA if formed, exceeding the mitochondria’s ability to metabolize it.

Sunday, February 3, 2013

Response to Dr. Paul Jaminet’s Rebuttal on Fructose



This rebuttal of sorts by Dr. Paul Jaminet was recently brought to my attention through a comment left on my Facebook page.  Danny Roddy was nice enough to lay out the arguments for me point by point.  Dr. Jaminet’s comments are in red.


1) “I think there’s substantial evidence that high fructose intake promotes endotoxemia” –PJ

This is not what I have found.

Diabetics and the obese have higher lipopolysaccharide (LPS) levels in their blood and they consume more fructose, primarily via HFCS, than people who are not diabetic or obese.   But as to specific food effects, the generation of LPS is buffered against on the ingestion of simple sugars because, for the most part, simple sugars are completely digested and absorbed in the upper part of the small intestines where microbial activity is minimal to non-existent. 

It is, however, conceivable that HFCS could lead to the generation of LPS because of the the presence of large starch molecules, if you recall.  Starch molecules, particularly when insufficiently cooked, can circumvent digestion and provide fodder for bacteria in the lower intestines, leading to the generation of LPS.

Endotoxemia occurs, though the definition is arbitrary, when blood levels of LPS rise by about 2- to 3-fold above normal levels.  Fats, in this regard, by permitting the passage of LPS into the body at high rates via newly made chylomicrons, execute the damages of LPS initiated by the increased proliferation of microbes in the intestines that was promoted by starches.