Podcast: Dr Lee Know: Mitochondria, Energy and the Theory of Aging

Today's interview is with Dr Lee Know. Dr Know is a licensed naturopathic doctor, recipient of several awards, and has held positions as medical advisor, scientific evaluator, and director of research and development for major organizations. He's the author of Mitochondria and the Future of Medicine (Chelsea Green Publishing, 2018), the Director of Scientific Affairs for Canada, and consultant to other natural health product brands.

1. Your book, "Mitochondria and the Future of Medicine," makes some pretty amazing claims about the importance of mitochondria to our overall health. You go into a lot of detail in the book, but for those who might not be familiar, could you just briefly explain what mitochondria are and what they do for us? The cell is comprised of different organelles: these are distinct structures that carry out specialized functions. The mitochondria is one of these organelles. Their main role is as a powerhouse for the cell: they produce energy. Everything that happens in the body requires an input of energy, and over 90% of that is produced by the mitochondria.
2. Along those lines: can you briefly summarize the Mitochondrial Theory of Aging? This theory has been around for a number of years now. It overcomes some of the issues with previous theories of aging like the free radical theory. It says that the health and function of the mitochondria within our cells is the biological clock. This looks at the health of the mitochondria and their ability to produce energy and meet the demands of a particular cell. There is a process that happens on the inner membrane of the mitochondria called the Electron Transport Chain: these pass electrons from one complex to the next. But if the electrons spill out, they will cause damage to the mitochondrial DNA. When the mitochondrial DNA is damaged, it can't produce proteins in the ETC anymore, and the mitochondrial production of energy will slow down. This will lower cellular health. It's the free radicals generated at the level of the mitochondria that have the greatest impact on aging. Those from exogenous sources have only a minor impact.
   1. Side note here: I thought the fact that babies have more UCPs to keep them warm fascinating! Didn't realize that brown fat was protective against degenerative diseases because the excess energy gets dissipated as heat rather than turned into free radicals, either. Very cool! Can you address what this means for certain populations in terms of exercise (and how important it is, relatively speaking?) Infants are able to maintain body temp bc they have a lot of brown adipose tissue or brown fat. The mitochondria is high in uncoupling proteins. Under normal circumstances, we create energy by the ETC, pumping protons into a space and those protons create ATP. UCPs uncouple the proton gradient and those protons will flow back through other channels. The result is heat. For infants, that's a way for them to generate heat. There's also research going on into how to increase brown fat in adults. People who have low brown fat and UCPs are more overweight. If we can increase this, we'll dissipate the proton gradient. This is how hibernating animals can go all year and hibernate in cold temperatures. This is why they eat such high fat diets to store up energy. Also talks about this with different populations. The Inuit in the far N have more uncoupling proteins than people who live closer to the equator. One of the ways we can increase brown fat is through cold exposure. Our bodies will adapt because of this. If you're from warmer climates, you don't want to generate more heat. This is why hydrotherapy is great!
3. One key insight in your book seems to be the feedback mechanisms involved in the mitochondria itself?and taking antioxidants may hinder this process (at least compared to reducing the free radical leakage in the first place, on uncoupling electrons from ATP production). Can you elaborate on this a bit? The free radicals that matter most are generated at the level of the mitochondria. Free radicals are generally thought to be negative, but in reality they have a positive aspect too. When put into context of what else is going on in the cell, these help our bodies adapt. You don't want to neutralize these. Controlled exposure to oxidative stress can increase life span. Training with exercise, for instance, generates free radicals, but when those are generated in that sense, they send a positive signal. According to the study, antioxidants during the training phase will blunt the response to that training.

1. You mention that the one proven way to extend life is calorie restriction in your book. Tell me a little more about why this is. Calorie restriction means fewer electrons enter the ETC and therefore fewer free radicals are created. This also turns certain genes on and off.
   1. But: CoQ10: this isn't a vitamin, we produce it ourselves. But it becomes more vitamin-like as we age bc our bodies produce less of it. Its role: it's a component of the ETC, accepts electrons from complex 1 and 2 and passes them to complex 3. Availability of CoQ10 can be a bottleneck in mitochondrial efficiency. You want an excess of this bc it's a busy molecule. It lowers in older people, especially people with certain health conditions. There are many studies now that have shown that when you supplement these people with CoQ10, you get the mitochondria working a lot better. Allows the cells to act more efficiently.
   2. Magnesium: numerous studies show that about 70% of the population doesn't even get the RDA amount. This is the minimum amount of a nutrient that prevents a deficiency syndrome in 98% of the population. This is minimum, not optimal amount. Magnesium is a cofactor in many different processes in the body. Many enzymes in the body need magnesium as a cofactor. ATP (Adenosine TriPhosphate) is actually magnesium ATP. Every molecule of ATP is attached to a magnesium. This is very important for energy production. People will often report that they feel less tired when they take it.
2. It seems your two favorite nutrients for mitochondrial support are CoQ10 and Magnesium. Is this true? And can you explain a little about why each is important, and who should be supplementing with them? There are a lot of nutrients out there that are still helpful besides these.
   1. Diastolic BP is the pressure when your cardiovascular system is at rest. This is a function of how elastic your blood vessels are and how well they can relax. Muscle relaxation actually takes more energy than muscle contraction. (An example of this: when we die, we're no longer producing energy and the muscles go into rigor mortis.) We have muscles surrounding all our blood vessels. When they don't have the energy necessary to relax, that's what causes the diastolic number to increase.
3. D-Ribose also gets a spotlight. What are some of the key features that make you consider this supplement for a patient? (And can you explain further the association between ribose and diastolic hypertension?) This is a 5-carbon sugar, not a 6-carbon sugar like glucose or fructose. This is very safe for diabetics and there's a potential that it could even lower blood sugar. D-Ribose is the backbone of the adenosine molecule that creates ATP. It's a critical building block of the molecule. Our bodies normally produce enough of this on its own ? don't necessarily need to supplement it. But in certain circumstances, the body can't produce it fast enough to meet the body's demands. That's why it's often recommended for Chronic Fatigue and fibromyalgia. Because we're constantly in a state where we're depleting adenosine, sometimes people just can't keep up with the demand. D-Ribose can help balance this. The ketogenic diet is very popular, but our bodies use glucose as a starting material to create D-Ribose; so if you're low on carb intake, you're starving the body for the building block for D-Ribose. For anyone going through ketosis, the addition of D-Ribose is helpful.
4. Can you explain the connection between glutamate, excitotoxicity, and declining neuronal cell energy? (And why this means MSG isn't a great idea?) MSG gets converted to glutamate in the body which is an excitatory neurotransmitter. Too much of this causes neurons to be in an excited state for too long a period of time. This adds stress, and the CNS is the most energy-intense system in the body. When you're exposed to glutamate, this will create stress that will lead to the energy molecules like ATP to be depleted. Sometimes with MSG after you eat, you'll have a rapid HR and sweating, which is because of the excitatory effects of glutamate, but then you deplete everything and wear out the neurons, and a few hours later, you get a very low energy level.
   1. Statins: these are the most prescribed drugs in the world to lower cholesterol. Assuming that you believe that cholesterol is an issue to begin with: these block the enzyme that produce cholesterol. This is why it's so effective in lowering cholesterol. The problem is, that same enzyme produces CoQ10. So this induces CoQ10 deficiency and sets you up for cardiovascular disease. Statins have no place in healthcare! If you're looking to lower cholesterol, there are natural ways to do it. But if you are taking them, you should be on CoQ10 too. You should also be on Vit D as well, since statins will also deplete this.
   2. Antibiotics: these are particularly damaging to mitochondria. Mitochondria were once individual bacteria, and antibiotics are great at killing bacteria?so mitochondria are therefore also susceptible. Antibiotics are also way overprescribed. They not only decimate the microbiome, but they can inflict significant damage on the mitochondria.
   3. Tylenol/Acetaminophen. This is considered the biggest cause of liver damage in the US and Canada from accidental overdose. It depletes our bodies' stores of glutathione. Glutathione is an incredibly important source of antioxidant support, and without it, the oxidative damage generated by the ETC can damage the DNA of the mitochondria, causing them to slow down and be less efficient.
5. What would you say are the top two or three most popular drugs that can disrupt mitochondrial function?
6. PQQ can actually stimulate the growth of new mitochondria?! Tell me more about this. (And it's high in chocolate - yay!!) PQQ is another interesting nutrient found in small amounts throughout the food chain. This was the first nutrient to show mitochondrial biogenesis. Prior to seeing this with PQQ, the only way to increase mitochondria was with physical activity. But we see it with PQQ too ? even without exercise.
7. What are other things to avoid (besides pharmaceuticals) to preserve mitochondrial health? Most standard toxins will have an impact: heavy metals, pesticides (another good reason to eat organic!). In a lab setting, some studies look at Parkinson's in a rat model and they use a pesticide to create mitochondrial damage so that they can then study the results! But we willingly consume them. The FDA is not looking at damage to the mitochondria, nor is the USDA. Artificial food colors are damaging as well.
8. Anything I haven't asked you that you want to make sure you communicate to our audience? Exercise is probably the most important thing you can do for your mitochondrial health. This is how our bodies adapt and get stronger. At rest, which is the bulk of the day, the metabolic demand on each individual mitochondria is considerably less. That's why there's the exercise paradox: physical activity does create a lot of free radicals, but those are the "good" ones and allow our bodies to get stronger. This is one reason why athletes have longer and healthier lives. One of the motivating factors for people to get up and get active is to understand the rationale.

Download the latest episode of Christian Natural Health!