Managing Your Mitochondria

In Monday’s “Dear Mark” post, I briefly outlined a few of the benefits to having healthy, abundant mitochondria, and in the past, I’ve alluded to the damaging effects of statins on mitochondrial function. All good, yeah, but a couple brief paragraphs in the middle of a Monday post aren’t enough. Mitochondrial function and mitochondrial biogenesis – the growth of new mitochondria – deserve more than that. Like, their own post. Today, I’m going to dig a little deeper. I’m going to lay out why growing more and healthier mitochondria (mitochondrial biogenesis) is good for your health, your longevity (and compression of morbidity), and your energy levels. I’ll explain why becoming a fat-burning beast optimizes mitochondrial function, and I’ll go over why this is so important if you’re looking to transform your body.

What’s funny is that we weren’t even “supposed” to have mitochondria, according to most scientists. Over a billion years ago – as the story goes – mitochondria were free-living prokaryotes (organism without a nucleus) making their own way in a pretty chaotic world with naught but their own DNA. Back then, everyone seemed to be uni- or multi-cellular, the oceans were crowded, and cell membranes were fluid (some might say downright porous), so there was a lot of casual interaction between eukaryotes (who had nuclei) and prokaryotes (who did not). Folks had no concept of condoms, of course, and eukaryotes have always been single-minded. A casual connection is made, a semi-porous membrane somehow gets a whole lot more porous, some enzymes are exchanged, and before you know it that little prokaryote has been engulfed by the eukaryote. It starts as sheer lust, but eventually turns into a lasting, mutually beneficial, endosymbiotic, loving relationship. The prokaryote becomes part of the eukaryote, contributes some DNA, changes its name to mitochondrion (hey, this was the swingin’ Proterozoic, when Prokaryotes’ Lib was going strong and where the lack of a nucleus didn’t preclude an organism from determining its own name) and starts producing energy for the cell – just like it did as an individual bacterium. The rest is history.

Fast forward to today, and mitochondria are present in nearly every cell in every organism in the world. Single-celled organisms might have but a single mitochondria, while individual human liver cells, for example, contain between 1000 and 2000 mitochondria each. They’re obviously pretty important.

I’d even venture a “very important.”

The primary role of mitochondria is to extract energy from nutrients to produce adenosine triphosphate, or ATP, which our body uses to create energy for a whole host of cellular processes. We are constantly using ATP, whether we’re sprinting, walking, breathing, pumping blood through our cardiovascular system, or doing long division. Think of a physiological process, and ATP is probably involved. Without mitochondria, then, we wouldn’t be able to get much of anything done. We simply wouldn’t be.

This whole ATP production process, however, comes with a hitch: the creation of free radicals. Whenever mitochondria produce ATP, whether from glucose or from fatty acids, free radicals are created as a byproduct. It sounds horrible, but they are an unavoidable consequence of ATP production, and healthy mitochondria can usually deal with a normal amount of free radicals (with the help of endogenous antioxidants like glutathione) before they do too much damage. If the free radical load is too great, however, either because you have too few mitochondria doing the work or because the mitochondria you have are not working properly, some will escape and do damage. Since free radicals have no electron, they will “steal” electrons from the first thing they encounter, stabilizing itself but rendering the victim unstable. Given free reign, free radicals can damage mitochondrial DNA (leading to mutagenesis, sap telomerase stores (remember, telomeres act as material for cell repair, so you don’t want to run out prematurely), oxidize proteins (including lipoproteins like LDL, which if oxidized can promote atherosclerotic plaque), and speed up the aging process by increasing oxidative stress.

It comes down a simple numbers game: the more mitochondria you have and the more efficient they work, the more spread out the workload. And when your mitochondria aren’t overburdened, there’s less free radical creation during ATP production. There’s less waste production.

The mitochondria’s other roles include, but are not limited to: steroid hormone (like testosterone and estradiol) synthesis, lipid metabolism, insulin/glucose regulation, and cellular calcium homeostasis. I’m a big fan of natural testosterone production (and estradiol’s not too shabby, either), metabolizing fat seems like a good thing to do, and I’m all for proper insulin sensing and glucose regulation. And cellular calcium homeostasis? Man, there is nothing quite like having adequate – not too much, not too little – calcium levels in my cells. Feels good.

By now, I imagine it’s become quite apparent that you want high numbers of high-functioning mitochondria in your cells. But how do you do it? How do you make your mitochondria work better? How do you make more mitochondria?

You have to understand how the body adapts to stress. When imposed demands challenge our bodies, our bodies make structural (and neurokinetic) changes to prepare for any future demands. Ergo, you lift something heavy for a few sets of five reps, and do so on a regular basis, and your muscles will grow, your bones will get stronger, and your connective tissue will adapt to deal with those heavy loads. Stress your body, recover from it, and grow stronger for next time. This is just how the body works. It adapts to what’s demanded of it.

It’s pretty similar for our mitochondria. When current levels and quality of mitochondria are inadequate to meet an imposed demand, we grow more of them and/or we improve the function and efficiency of the ones we have. When circumstances arise that require more or better mitochondria than we currently employ, the body will respond. We don’t make new mitochondria or improve our existing ones just for kicks, just like we don’t build lean muscle mass by sitting around. We have to give our bodies a reason to do it. We have to challenge our cells.

There are tons of supplements, including minerals, amino acids, and antioxidants, that boost mitochondrial function and even engage biogenesis, but I won’t get into that today. There are plenty of lifestyle modifications that challenge our mitochondria, especially physical activity. Resistance training and endurance training both improve mitochondrial function and increase mitochondrial resistance to degradation, and on Monday I mentioned how lifting heavy things and sprinting both increase mitochondrial biogenesis. But those are topics for another day, too.

The single most fundamental – and simple – way to improve mitochondrial function is to turn away from relying on sugar-burning and transform yourself into a fat-burning beast. See, mitochondria burn fatty acids cleaner than they burn carbohydrates. Generating ATP via fats/ketones produces fewer free radicals, because it’s more efficient, whereas generating ATP via carbs produces more. As a result, glutathione can do its job and our ketone-burning mitochondria have to divert less attention to cleaning up free radicals. This doesn’t just make mitochondrial ATP production from ketones more efficient; it has the potential to render it downright anti-inflammatory, too. When we dip into a full-fledged ketogenic diet, cut back on bad carbs, or intermittently fast, we are switching over to fat-burning. When we switch over to fat-burning, our mitochondria do the same. Heck, that’s what we mean by “fat-burning.” There’s even evidence that ketosis can spur mitochondrial biogenesis, albeit thus far only in rats.

In my new book I present my Primal prescription for becoming a fat-burning beast. In fact, one of the reasons I wrote the 21-Day Total Body Transformation is because untold millions of people are languishing in sugar-burning land and their mitochondria aren’t burning quite as cleanly as they could. The “transformative” aspect of the 21-Day Total Body Transformation is the epigenetic switch from sugar-burning to fat-burning. And improving mitochondrial function and (if that rat study pans out in humans) increasing mitochondrial biogenesis are at the heart of this switch.

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending more than three decades educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates flavorful and delicious kitchen staples crafted with premium ingredients like avocado oil. With over 70 condiments, sauces, oils, and dressings in their lineup, Primal Kitchen makes it easy to prep mouthwatering meals that fit into your lifestyle.

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