Overeating As a Source of Excess Oxidants
Overeating makes you age and get sick faster just like cigarettes
This is the fifth in a series of posts designed to help you understand how you can extend your healthspan and youthspan. In the last post, we reviewed very specifically how the oxidants in cigarette smoke switch on mTOR and switch off AMPK to cause cardiovascular disease and cancer. Now we are going to review how overeating does the same thing. It is all tied together, and we know how it works.
When you light a cigarette, you start a smoldering fire at the end. That fire oxidizes the tobacco, and it creates oxidative particles in the process. We use fire to create energy all the time. We burn gas to run our car motors. We burn coal to run our power plants. Oxidizing those fuels produces energy and oxidative particles. Our body works exactly the same way. We create energy by combining the carbon in gasoline, coal, or food with oxygen to produce carbon dioxide.
You probably remember mitochondria from high school biology. That is the energy producing unit in the cell. Sugar and fats travel through the blood stream to the mitochondria where they are oxidized to produce energy. In food, just as with fire, we combine oxygen with the carbon in food to produce carbon dioxide. Oxygen is essential to making energy by oxidation, but when we overeat, we produce more oxidants than our antioxidant defenses can handle. Those oxidants bind with proteins and DNA in the body to gum up the works. They break DNA strands to cause mutations that lead to cancer. Like the oxidants in cigarette smoke, these oxidants also activate the epidermal growth factor receptor (EGFR) to switch on mTOR and switch off AMPK.
There is another source of oxidants that are produced by overeating. If a patient with type 2 diabetes drinks a milkshake that contains 75% fat, 15% carbohydrate, and 10% protein, ADMA (asymmetric dimethylarginine) levels in the blood increased by two and a half times in just five hours. Ordinarily, the inner lining of our arteries produces the active ingredient in nitroglycerine (nitric oxide) and that dilates our arteries when we exercise to increase blood flow. Nitric oxide maintains arterial health. If you put nitroglycerin under your tongue, it relieves chest pain from a blocker heart artery. An ADMA increase shifts the inner artery from producing beneficial nitric oxide to producing oxidants which may even cause the artery to constrict during exercise. Oxidants damage the arterial wall and cause disease. This effect is so dramatic that 5 hours after drinking the milkshake, the percentage of dilation in the artery is reduced five fold.
This is especially fascinating because your body forms ADMA as part of genetic regulation. ADMA is produced by epigenetic activity. Drinking a milkshake very quickly raises ADMA levels in the bloodstream as a byproduct of the machinery of gene regulation. In keeping with everything that you have learned, the enzyme that makes ADMA is absolutely essential to normal fetal development. If the fetus does not have the main enzyme that makes ADMA as a byproduct of precise gene regulation, the fetus lasts only seven days after conception. It does not survive. It is another example that proves most chronic diseases and aging are the result of normal, essential genes that are abnormally regulated.
ADMA itself switches on 50 genes in the inner lining of the artery. Leading scientists at Stanford including Dr John Cooke have pointed to ADMA as an “uber marker” that is present in virtually all cardiovascular risk factors. “Associations between increased levels of ADMA and many cardiovascular risk factors such as age, hypertension, diabetes, insulin resistance, hypercholesterolemia (high cholesterol), hypertriglyceridemia (high triglycerides), and hyperhomocystinemia (high homocysteine) have been documented. Furthermore, evidence for a causal relationship between increased ADMA levels and endothelial vasodilator dysfunction (artery disease) has been demonstrated in many of these conditions.”
Concentrated liquid sugar and fat elevate ADMA levels and acutely reduce artery function. ADMA increases oxidant production which would activate the EGFR receptor to increase mTOR activity and inactivate AMPK just like cigarette smoke. There is yet another way that ADMA increases chronic disease, and that mechanism offers the most promise for treatment. ADMA is an amino acid that is an arginine derivative. Remember you learned that when you eat, amino acids like arginine switch on mTOR to coordinate growth with food supply. We know that ADMA does the same thing in certain circumstances. Metformin and ADMA are enough alike that metformin is like a baseball that fits in the receptor (catcher’s mitt) that activates mTOR. That is almost certainly the site at which metformin directly blocks the effect of ADMA to switch on mTOR. If metformin is in the pocket of the mitt and you try to catch ADMA, ADMA just bounces out and it does not switch on mTOR. That is how metformin slows down aging and chronic disease development. If you look at the diagram below, you will see that ADMA and metformin are exactly the same on one end. That is how metformin blocks the effects of ADMA.
Let’s review what you have learned about all the ways poor nutrition makes you age and get sick faster. When you eat, you directly activate mTOR and deactivate AMPK. If the meal includes carbs or sugar, that dramatically increases your insulin level which also switches on mTOR and deactivates AMPK because it is a growth factor. Overeating produces oxidants at the level of mitochondrial oxidation. It also produces ADMA which increases oxidant production and directly activates mTOR. The excess oxidants activate growth factor signaling through the epidermal growth factor (EGFR) just like cigarette smoke. There is one more way that diet contributes to aging and developing chronic disease faster, and that will be the topic of the next post.
This body of medical knowledge has not been translated into clinical practice in the United States yet. Most clinicians are unaware of this science. I learned most of it in the last ten years. I had to teach myself. It is a totally new way of looking at chronic disease and it would be shocking if you did not have questions. Please ask them. I appreciate any suggestions that you may have on clarifying some of these points. We can slow aging and delay chronic illness now.
Yup! 💯%!
Perfect for Friday. But you took all my fun away :)