The Mitchondrial Threshold

May 31, 2021

The Mitochondrial Threshold: The Explanation for All Diseases

How do you explain the root causes of diseases? What is the underlying cause? Let's take a stab at it. See if I can explain to you, in plain enough English the key ideas and have it make sense to you.

It helps to go backwards, so let's make one example: heart disease. A heart attack is actually the final end-product of 30 years of arteries accumulating lipids and small, dense LDLs stuffed full of triglycerides. But what got that started? We call it endothelial dysfunction, of which the very first step is the lining cells of arteries being stressed by too much peroxide. They can't neutralize it faster than it's being made. Peroxide comes from Reactive Oyxgen Species (ROS). (Very elegant research backin the 70s proves it.). So they stop being connected to each other and the artery lining gets leaky. In comes the LDLs. Let's go back another step. What makes the peroxide?

In short, oxidative stress. Now we are back to the mitochondria, our energy factories. Our mitochondria like a regular supply of fuel which they get fed via fatty acid breakdown in the peroxisomes or pyruvate via the glucose pathway. Those are like two separate hoppers, or supply trains, feeding raw energy into the engine. They work best when there is a gradient going downhill all the way through. The very first complex in the electron transport chain is Complex 1 which will push 4 protons into the "reservoir". Now, an active athlete is using up all their ATP in their cells, so the electron transport chain has something to do, a destination for its protons. Ditto for a person who is fasting. Very few protons linger in the "reservoir". The electron transport chain always has an empty slot for the next electron and proton. So, they all get used properly and no reactive oxygen species get pushed out. But what happens to a well-fed, middle class office worker who just had a big breakfast of sugar coated cereal and a luscious coffee purchased on the way to work with 600 more calories of high fructose corn syrup. With little calorie expenditure pulling ATP out of the mitochondria, and both sources of fuel wound up, the electron transport chain backs up. It has more fuel arriving than it can handle and it can't turn anything off. Its only way to cool off is literally to cool off, turn on uncoupling so it makes more heat. But that isn't enough. 

The backing up makes for more reactive oxygen species, (loose electrons that escape complex I and III in the electron transport chain). And that makes for more peroxide. Remember peroxide going out there and damaging your lipids and your endothelium, starting artery disease? It took 40 years for it to turn into a heart attack, but it started sitting in the booster seat in the back of the minivan stuffing your face with french fries and ketchup. They overwhelmed your mitochondria, flooding you with "oxidative stress". The fructose in the ketchup flooded your liver forcing you to make fat. Or in the sugared fruit drink that came in a pouch, or in a donut covered with sugar.

And that is the "Mitochondrial Threshold". Our modern food supply of too much nutrition, of too many kinds of foods, delivered all at once, without any fiber in it to nourish our gut and slow down the delivery of calories. Hence, the cause of all diseases is our modern food supply, delivered with too many purified calories, devoid of any fiber to slow their absorption. We have met the enemy, and it is us.

You can walk through this same scenario with cancer. Dysfunctional mitochondria, with altered internal dynamics pushing nutrients into alternative pathways. In the case of cancer, its citrate being exported into polyamines and feeding cancer.

But underlying all of them is the damage to the mitochondria that overwhelms the mitochondrial ability to repair its own membranes. What is in the mitochondrial membranes that is sucking up and absorbing the reactive oxygen species that gets overwhelmed?


What would happen if you maintained your plasmalogens? Plasmalogens are in place to catch the occasional reactive oxygen species with their precious vinyl ether bond on the outside of the membrane, the only membrane lipid to have such a feature. We deplete them with our modern, highly processed diet. Then, inexorable flooding of our mitochondria leads to mitochondrial dysfunction. Once upon a time we made sufficient plasmalogens to absorb the occasional reactive oxygen. Now, the ensuing flood of ROS leads to chronic disease. That's where diabetes,heart disease, neurodegenerative disease all start. How to repair? 

First! Don't produce so many reactive oxygen species by eating so much highly processed food that floods your mitochondria with too many nutrients all at once, and depleting your plasmalogens. Two, make sure you get the proper nutrients to make sufficient plasmalogens. Understanding how we deplete them and how plasmalogens create a means of measuring our biochemical reserve creates a whole new methodology of gauging susceptibility to chronic disease.

This hypothesis is the nexus of Robert Lustig's brilliant new book Metabolical. Read it. He has a chapter detailing the three great controlling enzymes that get overwhelmed by our eating processed foods. It's sobering and it fits the missing understanding of complexity. And he has a chapter about how to measure where you are. Get the lab.

My addition to this is my understanding Goodenow's contribution that I call the metabolic "shock absorbers" to dysfunction, plasmalogens. His book isn't published yet but this is some of the advanced ideas detailed in it. We can overwhelm our mitochondria in daily living, and our plasmalogens soak up the errors and neutralize the reactive oxygen species. Eventually we wear that reserve down. That's when trouble starts.

www.What will Work for me. Ah, I now understand why intermittent fasting works. You empty out your electron transport chain and allow your mitochondria to get back to running on lean. They like that. I also get how Goodenowe's discovery of plasmalogen absence predicts coming metabolic catastrophe. Their adequate presence means you still have metabolic resilience. They might just be considered your metabolic shock absorbers. The metabolism of fructose fits curiously into the picture as an accelerant, like pouring gasoline on a campfire. Then metformin speeds up your mitochondria to help them clean out. Exercise also gets you to running on lean. What gets you the sickest, fastest? Fast food. Lustig brilliantly simplifies his advice. " Feed the gut, protect the liver". That comes down to more fiber (known as whole food, vegetables and fruit) and less fructose. That comes down to less processed food. Hereafter I'm ordering the GGT enzyme in addition to the AST and ALT so I understand Lustig's lab. I've measured my plasmalogens. I was low. I'm now taking them as a rebuilding plan. My mitochondrial threshold lies in the balance. My brain, my pancreas, my liver, my heart all lay in waiting.

References: Br J Pharm, Nephrology Dial Trans, Atherosclerosis, Metabolical,

Pop Quiz

1. Step one in getting in trouble is? Answer: Per Lustig, what we put in our mouth in the form of highly processed food that gets too many nutrients into our cells too fast.

2. What is Lustig's simple admonition about eating: Answer: Feed the gut, protect the liver. (Aka, more fiber, less sugar)

3. What correlates the best pending vascular disease? Answer: Low plasmalogens.

4. And just what role do plasmalogens play in this whole dance? Answer: They are your metabolic shock absorbers, soaking up excess free oxygen radicals.

5. Can you overcome them? Answer: Have you watched the movie "Supersize Me."? Yes, we all are routinely engaged in that practice with our low fiber, highly refined, western diet choking us with too much sugar.