The Powerhouse of Cells
Revving up the mitochondria to maximize health, energy levels, prolong your life span, and fight cancer
Written by: Joachim Bartoll, November/December, 2015
Classic Muscle Newsletter, February 2016 (issue #17)
Mitochondria are tiny double membrane organelles that produce ATP (the energy currency of the cell), through respiration, and to regulate cellular metabolism. Red blood cells and skin cells have very little to none, while germ cells have 100,000, but most cells have one to 2,000 mitochondria in them. They're the primary source of energy production for your body.
Since mitochondrial function is at the very heart of everything that occurs in your body, optimizing mitochondrial function is extremely important for health and disease prevention.
For example, one of the universal characteristics of cancer cells is they have serious mitochondrial dysfunction with radically decreased numbers of functional mitochondria. While the mitochondria can still function in cancer cells, cancer cells become dependent on glucose instead of ATP (the Warburg effect) and the mitochondria is shut down.
How the mitochondria produce energy
To produce energy, your mitochondria use glucose, fatty acids, amino acids, and other cellular materials from the food you eat, and oxygen from the air you breathe to produce ATP through a series of biochemical processes known as oxidative phosphorylation. Your mitochondria have a series of electron transport chains in which they pass electrons from the reduced form of the food you eat to combine it with oxygen from the air you breathe and ultimately to form water. This process drives protons across the mitochondrial membrane, which recharges ATP (adenosine triphosphate) from ADP (adenosine diphosphate). ATP is the carrier of energy throughout your body.
However, that process also produces byproducts such as reactive oxygen species (ROS), which are damaging to your cells and to your mitochondrial DNA. These damaging effects are then transferred to your nuclear DNA.
In other words, there’s a trade-off. In producing energy, your body also ages from the damaging effects of the ROS. How quickly your body ages largely depends on how well your mitochondria work, and how much damage can be minimized by diet optimization. The better your mitochondria work, the less ROS are produced, and the better your diet is, the more protection it can offer against the produced ROS.
The mitochondria and cancer
Cancer is caused by mutations and altered gene expression, in a process called malignant transformation, resulting in an uncontrolled growth of cells. When cancer cells are present within the body, the ROS produced as a byproduct of ATP production normally send a signal that starts a process of cellular suicide, also known as apoptosis. Since you generate some cancer cells every day, this is a good and necessary process. By killing off damaged cells, your body can replace them by new healthy cells.
The problem however, is that cancer cells is not using its mitochondria, and thus not producing those reactive oxygen species any longer. The cancer cells can no longer be destroyed by the body, and an uncontrolled growth take place.
The mitochondria and ageing
Currently, the cellular disorganization of ageing is generally accepted to be linked to the oxidative stress caused by free radicals and other reactive oxygen species (ROS). Also widely accepted is the key role of the mitochondrial genes of differentiated cells as the main target of ROS attack, according to the oxygen stress/mitochondrial damage theory.
Aging corresponds to a breakdown of that balance, when the accumulation of damage exceeds repair capacity. In the loss of dynamic equilibrium involving the following factors:
- The normal process of energy production in our cell generates reactive oxygen species (ROS), which disrupt all cellular components, especially DNA contained within the mitochondria. Since mitochondrial DNA encodes energy production machinery, these components accumulate alterations that help reduce their functionality. When ATP production decreases below a threshold, the cell does not have jurisdiction, so that the process of cell death by apoptosis is triggered. This causes the decrease of energy.
It has been estimated that each DNA molecule, contained in each of our cells, is object of 10,000 attacks per day, by free radicals.
- Sugars can react with amino acids, proteins, nucleic acids, and lipids of our body, causing injuries to ur cells. It can also cause a synergistic effect with oxidation by ROS that is known from glycoxidation. The glycoxidation is involved in numerous pathological conditions associated with aging and / or diabetes, such as Alzheimer's disease, atherosclerosis, kidney disease or peripheral vascular disorders, among others.
- Unlike cancer cells, which multiply indefinitely, normal cells have limited proliferative capacity: this phenomenon has been associated with the decrease in telomere length, which are located at the ends of chromosomes. Telomeres are cut at each cell division. When the telomeres reach a critical size, a response to DNA damage, dependent tumor suppressor gene, named p53, which triggers cell death by apoptosis is activated. In general, this p53-dependent mechanism, is activated when any kind of oxidative DNA damage occurs, in addition to other genetic alterations.
In other words, by keeping our mitochondria healthy and thereby ROS production to a necessary minimum, while limiting sugars and getting plenty of antioxidants, we might be able to slow down the process of ageing.
The mitochondria, muscle mass and exercise
The density and health of the mitochondria in your organs and muscles are, to a large extent, a reflection of your current level of health and fitness. Lean muscle tissue, for example, contains far more mitochondria than fat does, and a strong heart is likely to be denser with mitochondria than a weak one. The more healthy and functional mitochondria your body contains, the better you’ll feel, and the better your metabolism will be. Healthy mitochondria translates to better energy and focus, and greater ability to sustain high levels of activity without fatiguing.
A dysfunctional mitochondria trigger catabolic signaling pathways that tell the nucleus to promote the activation of muscle atrophy. Exercise, on the other hand, improves mitochondrial function by activating mitochondrial biogenesis and mitophagy, possibly playing an important part in the beneficial effects of physical activity in several diseases.
How to rev-up our mitochondria: feeding strategies
As previously mentioned, a major side effect of ATP generation is that some electrons leak from the electron transport chain, and those electrons react with oxygen to form free radical superoxides. These oxygen free radicals attack the lipids in your cell membranes, protein receptors, enzymes, and DNA that can prematurely kill your mitochondria.
Some free radicals are actually good and your body requires them to regulate cellular function, but problems develop when you have excessive free radical production. Sadly that is the case for the majority of the population and why most modern diseases, especially cancers, are becoming more and more prevalent. There are two possible solutions to this problem:
- Increase your antioxidants through food and supplementation
- Reduce mitochondrial free radical production by limiting its fuel
The most effective way to reduce excessive free radical production and to extend the healthy life of the mitochondria, and thus decreasing the risk of disease and prolonging life, is to limit the amount of fuel you feed your body. We already know that calorie restriction has consistently shown many therapeutic benefits. However, if you pursue a healthy strong and muscular body, year-round calorie restriction doesn’t really cut it. We also know that protein is a key factor in ageing.
So, what to do?
This is where variations of Intermittent Fasting comes into the picture. By limiting the time-window when you feed, you effectively reduce both the time-window and the number of times your body has to handle food, which is the main source of free radical production. And by limiting the time you have to feed, you’ll also effectively limit the amount of food you’ll be able to eat – reducing the risk of overeating and gaining too much body fat while pursuing new muscle mass.
Another positive effect of limiting your feeding-window is that your mitochondria get more efficient after a window of fasting – producing less ROS once you feed again, especially over time. Another benefit from fasting 16 hours or more is the up regulation of autophagy. Autophagy is the process of eliminating damaged cells. When a cell is damaged, it can die and be replaced. But sometimes it doesn’t die and it becomes what is called a senescent, and this happens a lot with aging and when autophagy is impaired. What that means is that the cell is not dead but it’s not really alive either. It’s not doing its function. It is just sitting around in your body secreting pro-inflammatory molecules, damaging other nearby cells, and thereby accelerating the aging process. Autophagy clears away those cells that are just sitting, which is a very important biological mechanism for staying healthy.
If you’re carrying a lot of muscle mass or desperately want to gain muscle, following a strict Intermittent Fasting protocol will not be ideal. In actuality, it might be disastrous for your gains. If you need 3500, 4000, or more kilocalories a day, eating only two meals and chugging down some para-workout nutrition will not cover it. And even if you would manage, your digestive system would collapse. In these scenarios, the best thing you can do is to put off your first meal by a few hours. Eating your first meal at lunch is way better for your long-term health than eating first thing in the morning. Although it might not be as effective as fasting for 16 or 18 hours or more, there are additional ways to fight ROS and help our mitochondria.
Nutritional strategies and supplements
Once you have decided upon a feeding schedule and frequency that fit your lifestyle and physique goals, the next step is to take a look at what you eat. The most important nutrients for cell- and mitochondrial health are:
- Omega-3 fatty acids
- All B-vitamins, including B6, riboflavin and thiamine
- Alpha-lipoic acid (ALA)
- L-Carnitine (needed for fatty acids to enter the mitochondria)
- D-ribose (raw material for ATP-molecules)
- CoQ10 or Ubiquinol
The best way to obtain the majority of these are through whole foods as they contain other nutrients and fiber that will help with absorption. Depending on your love for vegetables, nuts, seeds, and fruits, you might want to consider some in supplement form. Especially a B complex, a good omega-3 supplement and perhaps magnesium if you’re very active (as most people are deficient in magnesium). If you experience a lot of stress, CoQ10 or Ubiquinol could be a good addition during such periods in your life.
Another step is to take a hard look at your diet. The empty calories of sugars, flours, and other processed foods, force the mitochondria to burn through a lot of unnecessary junk – generating free radicals and inflammation – before useful nutrients can be siphoned out and used.
And if you’re past middle-aged and suspect that your insulin sensitivity is impaired, and/or if you’re overweight, reducing your carbohydrate intake might be a wise step. There’s actually evidence that a ketogenic diet may be the best way to go if you’re insulin resistant (or have diabetes) and sluggish mitochondria. A ketogenic diet (without carbohydrates) will re-teach your body to use fat as fuel, increasing fat burning and reducing inflammation.
Even if you’re younger, focusing your carbohydrate intake around and after exercise is always best. The old saying, “earn your carbs”, still holds a lot of merit.