Mitochondria are the power plant of each cell, being the primary site of ATP energy production. These cellular organelles, which number in the hundreds or thousands in every cell, accumulate in muscle, notably the heart.  

That makes mitochondria particularly important in cardiovascular health. With aging, mitochondria also age, resulting in the deterioration of skeletal and cardiac muscle. But mitochondria are more than just energy creators. Mitochondria have also been found to control apoptosis, or cell survival and clearance of dead cells.  

The mitochondrial theory of aging implies that impaired mitochondrial function contributes to age-related diseases. Recently, mitochondria have also been found to be important in metabolism, particularly in the context of the aging process—both health span as well as life span. A handful of nutrients can optimize mitochondrial function and even create new mitochondria. Here are three to consider when formulating mitochondrial-activating supplement lines.  

CoQ10: Coenzyme-Q10 is a fat-soluble antioxidant that regenerates vitamins C and E after they quench free radicals. But it is most well-known for being an electron and proton carrier of the mitochondrial respiratory chain and thus vital for mitochondrial bioenergetics. Simply put, it is the energy currency. It is found in particularly high levels in heart tissue. It has been shown to protect the heart during cardiac surgery, end-stage heart failure and cardiopulmonary resuscitation, and has been shown to improve heart function. In healthy people, coQ10 has been found to reduce mental and physical fatigue.  

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Statin drugs, which notch  $15 billion in global sales every year, are used to lower LDL cholesterol levels. Statins are also known to damage mitochondria, manifesting as muscle soreness at a minimum and heart failure as a worse-case scenario, making coQ10 the supplement every cardio patient on statins should take.  

The traditional form of coQ10 is the oxidized form, ubiquinone, though the reduced form, ubiquinol, has come on the market in the last 10 years and is said to be more bioavailable. CoQ10 is a large molecule and companies employ various technologies to improve bioavailability to positive effect—as much as 2.4 times higher using some technologies, 4.3 times higher in others. Without these bioavailability-boosting ways, the dosage of coQ10 is typically seen as 100 mg for a maintenance dose and 300 mg for a therapeutic dose.  

PQQ: Where coQ10 is good for mitochondria activation, PQQ (pyrroloquinoline quinone) is good for mitochondrial biogenesis—i.e., it makes new mitochondria. Cool, right? Like coQ10, PQQ is also involved in cellular energy metabolism. One human clinical study on 17 adult subjects found 20 mg—the dosage used in all human studies, not the 10 mg that is found in all too many supplement formulations—for 8 weeks led to improved stress, fatigue, quality of life and sleep. Another 20 mg study found improved attention and working memory in elderly people after 12 weeks. 

The Q’s have it—formulate with coQ10 and PQQ together!  

Niacin: Mitochondrial metabolism is intertwined with the universal coenzyme NAD as all NAD activity takes place in mitochondria. There’s a great deal of sex appeal lately in longevity ingredients nicotinamide riboside and NMN (nicotinamide mononucleotide). The latter was a recent recipient of a successful new dietary ingredient notification to the Food and Drug Administration, which later reversed course and said NMN cannot be lawfully marketed in dietary supplements because it was subject to clinical research by pharmaceutical interests—the same "drug preclusion" rationale the FDA used to try to put the lid on hemp-derived CBD and N-acetyl cysteine (NAC).

NAD+ levels by middle age decline to half the youthful peak levels. Increasing NAD+ levels have been shown to reverse mitochondrial dysfunction and even extend lifespan in animal models. NMN, meanwhile, rapidly converts to NAD+ (in rodent studies). NMN has also been shown to restore skeletal muscle mass (albeit at a crazy-high dose of 500 mg/kg). These are still early days in NAD+ and NMN research, with researchers mostly studying effects in animals. The problem for healthy aging supplements formulators is that nicotinamide riboside (which is an NAD+ precursor) is expensive and NMN is technically illegal (though that same FDA "drug preclusion" determination certainly hasn’t stopped CBD from being marketed). But a 2020 study from Japan found that niacin—good ol' vitamin B3—has the ability to increase NAD+ levels by a whopping 30-fold in only 30 minutes. All that, and at a dose of only 200 mg! Skin flushing with niacin, of note, can occur at doses of as small as 30-50mg. However the form of niacin known as nicotinamide, typically used in supplements and also referring to the amide form of vitamin B3 (niacin), does not cause skin flushing. That makes niacin a kind of poor man’s NAD+ precursor that ameliorates mitochondrial damage and is a central to energy metabolism.