Eades: "It's The AMPK Activity, Stupid"

When viewed from this perspective, it’s pretty easy to see why AMPK activated by a calorically-restricted diet and/or exercise brings about many healthful changes. It also might make one wonder why drugs haven’t been developed to increase the activity of AMPK to provide these same benefits to people who suffer from obesity, high blood sugar, diabetes and all the other disorders caused by overnutrition. A drug designed to activate AMPK would be diet and exercise in a pill. Who wouldn’t want that?

Well, there are several such drugs. Most have probably heard of one of them: metformin (trade name Glucophage.) Metformin, derived from an ancient herbal remedy, is used by doctors to treat diabetes and insulin resistance and works by activating AMPK. In 2010, physicians wrote some 100 million prescriptions for metformin to treat type 2 diabetes.(5) Some use it to treat obesity, and many folks who can get access to it, take metformin in hopes of increasing longevity.

Drugs that increase the activity of AMPK, when used over time, along with all the effects mentioned above tend also to increase the number of mitochondria, which increases the capacity to burn fat and turn it into ATP. More mitochondria leads to improved endurance, and, consequently, many of these drugs have been placed on the banned list of the World Anti-Doping Agency, the regulating body that deals with drug abuse in sports.(7)

http://www.proteinpower.com/drmike/inflammation/can-your-food-make-you-fit/#more-4858

Dr. Mike Eades digs in deep in this post, and explains, in a relatively simple way, a very complex topic, that being enzymatic function in metabolism.  You don't need to know this kind of stuff to avoid high density carbs, but it was interesting to see how he explains another piece of the low carb puzzle.  And if you were ever put on metformin, this post will explain why it should have helped with blood sugar issues - any why carb restriction and fasting would work even better.

The short explanation - AMPK signaling starts a chain of healthful benefits when cells go through a period of greater ATP consumption than creation.  When you restrict carbs/kcal, or increase the time between meals, AMPK signals for beneficial effects such as:

• Increases glucose uptake: We want to get glucose out of the blood and into the cells to burn.
• Increases glycolysis: We need to break down glycogen (stored sugar) to get the glucose to burn.
• Increases fatty acid oxidation: An obvious one. We want to start burni ncreases glucose uptake: We want to get glucose out of the blood and into the cells to burn.
• Increases glycolysis: We need to break down glycogen (stored sugar) to get the glucose to burn.
• Increases fatty acid oxidation: An obvious one. We want to start burning fat to replenish the depleted energy stores.
• Increases mitochondrial biogenesis: we want to make more mitochondria to burn fat and generate as much ATP as possible.
• Inhibits gluconeogenesis: We don’t want to spend energy making more sugar – we want to burn it.
• Inhibits glycogen synthesis: Same thing – we don’t want to store sugar, we want to burn it.
• Inhibits fatty acid and cholesterol synthesis: We don’t want to spend energy making fat and cholesterol.
• Inhibits insulin secretion: We want insulin to be low, so that we can move stored fat and sugar to where it needs to be burned.ng fat to replenish the depleted energy stores.
• Increases mitochondrial biogenesis: we want to make more mitochondria to burn fat and generate as much ATP as possible.
• Inhibits gluconeogenesis: We don’t want to spend energy making more sugar – we want to burn it.
• Inhibits glycogen synthesis: Same thing – we don’t want to store sugar, we want to burn it.
• Inhibits fatty acid and cholesterol synthesis: We don’t want to spend energy making fat and cholesterol.
• Inhibits insulin secretion: We want insulin to be low, so that we can move stored fat and sugar to where it needs to be burned.

A small point of clarity - none of this is anything other than interesting, except that it shows why carb restriction and fasting has a beneficial effect.  It's not a question of whether those techniques are useful to a large number of folks - that is already known.