Managing Your Mitochondria: Nutrients and Supplements

In last week’s mitochondria post, I explained how burning fat for energy was the foundation for keeping your mitochondria plentiful, happy, and robust. If you can’t access fat for energy, your cellular power plants will not work as well as they can or should. Any mitochondrial health regimen must include that as a basic precept. Once you’ve firmly established your fat-burning beasthood, though? You’ve got to man the power plant with a competent workforce. In putting together your workforce, there are plenty of factors to consider, including micronutrient status, supplementation, and exercise, all of which play huge roles in the health of your mitochondria. Rather than hire Homer Simpson, Lenny, and Carl to run the plant, you basically want a bunch of Frank Grimes.

So, without further ado, let’s dig in to the nutrient and supplement side of things.


Ah, magnesium, darling mineral of the Primal world, participant in nearly every physiological function known to man, and now essential cofactor for proper mitochondrial function? Yes, I believe so. Magnesium deficiency led to decreased mitochondria-per-cell count and increased size of individual mitochondrions in liver and kidney cells, which indicates that not only did low magnesium drop the overall number of mitochondria, but also increased the workload of the remaining mitochondria. Eat plenty of leafy greens, the occasional handful of nuts or seeds, and a starchy tuber when it suits you, taking care to supplement with a good magnesium -ate if you need it, and you should be fine on magnesium.

Zinc and Iron

Deficiencies in both zinc and iron can reduce the mitochondria’s ability to synthesize heme, which leads to oxidant leakage (the increased free radicals that I mentioned in last week’s post), “DNA damage, neural decay, and aging.” Luckily, zinc and iron are present in animal products and shellfish, so few Primal eaters run the risk of severe deficiencies. If you need to, supplement, but do so wisely: zinc toxicity alters mitochondrial metabolism and lowers ATP production in liver mitochondria. The liver processes both fats and sugars and healthy liver mitochondria are crucial for that important task.


You don’t hear a lot about manganese, but it plays a role in creating a potent mitochondrial antioxidant: manganese superoxide dismutase. Without adequate manganese, you won’t make enough superoxide dismutase, and without enough mitochondrial manganese superoxide dismutase, you run the risk of developing a neuropathology or suffering an ischemic brain injury (what often happens after stroke). Eat your mussels, raspberries, and dark chocolate.


In rats with a genetic predisposition to developing Alzheimer’s disease, supplementing with carnosine reduced the prevalence of classic AD hallmarks, the first and foremost of which was mitochondrial dysfunction. Carnosine is a potent scavenger of free radicals, and it’s a dipeptide of the amino acids beta-alanine and histidine. Meat eaters get plenty of carnosine, but supplements exist if you want to go that route.


Carnitine is biosynthesized from methionine and lysine, two amino acids which are highly prevalent in red meat, and your mitochondria like a lot of carnitine because it’s required for shuttling fatty acids into the mitochondria for processing. Yeah, if you want mitochondria to do one of their most basic jobs – break down fatty acids for energy – you better consume ample amounts of meat, or supplement with L-carnitine.

Vitamin A

Vitamin A deficiency caused oxidative damage to liver mitochondria in rats. Folks, in addition to handling fat and sugar metabolism, liver mitochondria also process ammonia, a potentially toxic byproduct of protein metabolism, so you’d better eat your egg yolks and liver and even cod liver oil along with your egg whites and steak and cod filets.

Vitamin C

Vitamin C is a universal antioxidant, internally produced by most organisms (except for us and a couple others), and it should come as no surprise to learn that it (along with resveratrol and alpha-lipoic acid) reduces excessive reactive oxygen species production by the mitochondria. It does so by increasing manganese superoxide dismutase (remember that?). Just be careful about supplementing during heavy cardio, as vitamin C has been shown to dampen mitochondrial biogenesis by interfering with normal cellular adaptations to endurance exercise. Maybe that was the problem back in my endurance days when I was downing 25,000 milligrams of C a day during training (hey, Linus Pauling said to supplement vitamin C “to bowel tolerance.” How times have changed.) I doubt sticking to natural sources of vitamin C, like fruit, raw meat, or fresh vegetables would have the same negative effect on exercise adaptation.

Coenzyme Q10 (CoQ10)

Our bodies make CoQ10, which is required for the transfer of electrons during mitochondrial oxidative respiration. Mitochondrial oxidative respiration is how we produce ATP for bodily functions and day-to-day life. Without enough of it (maybe we’re taking statins, which block the pathway responsible for synthesizing CoQ10, or we’re not eating enough foods high in CoQ10), our mitochondria’s ability to make ATP suffers, since CoQ10 is the only compound that can do its job. The best dietary sources of CoQ10 include animal hearts (since hearts need a lot of CoQ10 to generate the energy required to function), sardines, and virgin red palm oil. Even so, it’s still tough to get significant CoQ10 from food, which is why I like to supplement it.

Pyrroloquinoline quinone (PQQ)

PQQ is a bacterial biofactor present in soil, on plants, and in animals. It stimulates plant and bacterial growth, and when animals eat the plants (or soil) that contains the bacteria, they also get the PQQ. Biofactors extremely similar to PQQ have even been detected in interstellar dust, suggesting that it has been an important component of the global ecosystem for billions of years. As is the wont of other bioactive compounds with similarly expansive legacies and ubiquitousness (sunlight/vitamin D comes to mind, as do essential minerals), PQQ appears to interact with a number of physiological processes, including both mitochondrial function and biogenesis. It improves mitochondrial respiratory control and stimulates mitochondrial biogenesis. One could probably write an entire article on this stuff’s interactions with the mitochondria, and I won’t, but I will direct interested parties to a comprehensive paper on the subject (PDF). Most folks focus on supplementing with PQQ, which can be a bit expensive, but another option is to eat natto (fermented soybeans, a legume, but a highly nutritious form that contains vitamin K2 in addition to PQQ) and drink green tea, both of which are high in PQQ.


Resveratrol is the darling of the life extension set, and while I think some of its effects might be overstated, it does appear to improve mitochondrial function (in mice) and induce mitochondrial biogenesis (in rodent epithelial cells, the cells that comprise the lining of blood vessels). Furry little humans mice are not, but it’s interesting nonetheless.

Alpha-lipoic acid

Naturally occurring most richly in heart, liver, kidney, spinach, and broccoli, lipoic acid supplements have been shown to reduce mitochondrial decay in humans. Another study, albeit in rats, found that alpha-lipoic acid, along with a few other “mitochondria supportive” supplements, improved rats’ athletic performance and recovery. In both cases, it stimulated mitochondrial biogenesis.

I’m sure there are more nutrients, minerals, vitamins and supplements that affect mitochondrial function, but this is a decent list to consider when trying to man your cellular power plant workforce. And I bet if you take care of the bulk of these, either by eating good food or supplementing, you can keep a couple Homer Simpsons around for comic relief without too many problems.

For the next installment (sometime next week) in Managing Mitochondria, I’ll be covering exercise. Til then, take care and Grok on!

TAGS:  smart fuel

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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