Mitochondrial health describes how well your mitochondria, the small structures inside cells that turn food and oxygen into usable energy, keep doing that job. It matters because almost every tissue depends on them. The strongest human evidence for supporting mitochondria points to regular exercise; evidence for supplements is much thinner.
Key Takeaways
- Most cells contain hundreds to thousands of mitochondria, which make ATP, the cell's main energy molecule, through oxidative phosphorylation.
- Endurance and interval training increase mitochondrial content and function in human muscle, including in older adults.
- Mitochondrial ATP production in muscle tends to decline with age, and the decline tracks with lower aerobic fitness.
- CoQ10, NAD+ precursors, creatine, alpha-lipoic acid and PQQ all have real roles in energy metabolism, but human trials on whether supplements improve mitochondrial function are small and short.
- Diet, sleep and activity form the foundation; supplements are optional extras, and you should check with a clinician if you take medication.
Evidence grade: Moderate. Exercise training has consistent human trial evidence for increasing muscle mitochondrial content and function, while human studies of supplements for mitochondrial function are few, small and short.
What Mitochondria Do
Mitochondria are found in nearly every cell, often in the hundreds or thousands [4]. Their main job is oxidative phosphorylation, a process that uses oxygen and the breakdown products of food to make adenosine triphosphate (ATP), the cell's main energy source [4].
Mitochondria also carry their own DNA. It holds 37 genes, and 13 of them code for enzymes used in oxidative phosphorylation [4]. The rest of the proteins mitochondria need come from genes in the cell nucleus.
Tissues that work hardest carry the most mitochondria. Heart muscle is a striking example; read why the heart has more mitochondria for the details.
What Affects Mitochondrial Health
Exercise training
Exercise has the best human evidence of anything that influences mitochondria. A 2018 review in Sports Medicine found that endurance training increases mitochondrial content and respiratory function in human skeletal muscle. Training volume seemed to be the key driver of how many mitochondria muscle builds, while relative intensity drove how well they work [6].
A 12-week trial at the Mayo Clinic compared high-intensity interval training (HIIT), resistance training and combined training in younger and older adults. All three improved insulin sensitivity and lean mass, but only HIIT and combined training improved aerobic capacity and muscle mitochondrial respiration. In older adults, HIIT reversed many age-related differences in mitochondrial proteins [7]. For workout ideas, see the best exercise to increase mitochondria.
Aging
In a study of 146 healthy adults aged 18 to 89, mitochondrial DNA and the rate at which muscle mitochondria produced ATP both declined with age. Mitochondrial ATP production was closely linked with aerobic capacity [8]. Because exercise can improve mitochondrial respiration even in older adults [7], staying active remains the most practical lever.
Diet, sleep and stress
Mitochondria depend on nutrients from food, including B vitamins that become energy coenzymes. Niacin, for example, is converted into NAD, which more than 400 enzymes require [2]. A varied diet with enough protein, vegetables, whole grains and healthy fats supplies most of these. Sleep and stress are widely discussed as factors too, but direct human evidence on how they change mitochondria is limited, so this article does not make specific claims about them.
Supplements Most Discussed for Mitochondria
Several supplements are marketed for mitochondrial health. Each has a genuine role in energy metabolism, but having a role in the body is not the same as proof that taking more helps. Here is how the human evidence stacks up.
| Supplement | Role in mitochondria | Human evidence | Evidence level |
|---|---|---|---|
| Coenzyme Q10 | Essential part of the mitochondrial electron transport chain; also an antioxidant; made by all cells [5] | Many trials, mostly in people with specific health conditions; NCCIH rates results for several outcomes as inconclusive [3]; does not directly improve exercise performance [1] | Emerging for mitochondrial function in healthy adults |
| NAD+ precursors (such as nicotinamide riboside) | Forms of niacin that the body converts into NAD, used by more than 400 enzymes [2] | In 12 older men, 1 g a day for 21 days raised muscle NAD+ metabolites but did not change mitochondrial bioenergetics [9] | Emerging |
| Creatine | Raises phosphocreatine, which quickly regenerates ATP during short, intense effort [1] | Consistent trials show better performance in repeated short bursts such as sprinting and lifting; little value for endurance [1] | Strong for short-burst performance; not shown to increase mitochondria |
| Alpha-lipoic acid (ALA) | Essential cofactor for mitochondrial enzymes including pyruvate dehydrogenase; made in the body [10] | Safety well studied across 71 trials [11]; little direct human data on mitochondrial function | Emerging |
| PQQ (pyrroloquinoline quinone) | Studied in animals for effects on energy metabolism [12] | One small study of 10 adults found urinary changes consistent with mitochondria-related metabolism after 3 days [12] | Emerging |
Coenzyme Q10
CoQ10 shuttles electrons in the electron transport chain, the final stage of ATP production, and acts as an antioxidant [5]. The body makes it, and it is also sold as a supplement [3]. A 2018 review of clinical trials concluded that larger and longer studies are still needed in many areas [5]. To go further, read how to get CoQ10 naturally.
NAD+ precursors
NAD+ is a coenzyme made from niacin and related forms, including nicotinamide riboside (NR) [2]. Precursor supplements aim to raise NAD+ levels. The best-designed human data are still small. In a randomized crossover trial of 12 older men, NR at 1 g a day for 21 days raised NAD+ metabolites in muscle, yet it did not change how well their mitochondria produced energy [9]. One author disclosed ties to an NR supplier. For background, see what NAD+ is and how NAD+, NMN and NR compare.
Creatine
Creatine is one of the most thoroughly studied supplements. It works mainly outside the classic mitochondrial pathway, by storing phosphocreatine that can rapidly rebuild ATP during intense effort. The NIH notes that it helps repeated short bursts of high-intensity activity but has little value for endurance sports [1]. A common protocol is 3 to 5 g a day, sometimes after a short loading phase [1].
Alpha-lipoic acid
Lipoic acid is a required cofactor for several mitochondrial enzymes, including pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, which connect fuel breakdown to energy production [10]. Your body makes it. A 2020 meta-analysis of 71 placebo-controlled studies found that ALA supplements were not linked to a higher risk of side effects [11]. Whether extra ALA improves mitochondrial function in healthy people has not been well tested.
PQQ
PQQ has been studied in animals for effects on energy metabolism. Human data are very limited. In a 2013 study of 10 adults, PQQ at 0.3 mg per kilogram of body weight daily for about three days changed urinary markers in a way the authors described as consistent with enhanced mitochondria-related function [12]. That is an early signal, not proof of a benefit.
Safety and Interactions
- CoQ10: No serious side effects have been reported; mild insomnia or digestive upset can occur. Talk to your doctor or pharmacist if you take warfarin or insulin, or if you are receiving cancer treatment [3].
- Creatine: Considered safe for short-term use by healthy adults. It often causes weight gain from water retention [1]. Talk to your doctor if you have kidney concerns before using it.
- Alpha-lipoic acid: Trials have not found a higher rate of side effects than placebo [11]. Talk to your doctor or pharmacist if you take any prescription medication.
- NAD+ precursors and PQQ: Human safety data come from small, short trials [9][12]. Long-term safety is not established.
If you are pregnant or breastfeeding, have a medical condition, or take prescription medicines, talk to your healthcare provider before starting any of these supplements.
Frequently Asked Questions
What is the best way to improve mitochondrial function naturally?
Regular exercise. Human studies show that endurance and interval training increase the amount and function of mitochondria in muscle, and the effect appears in older adults too. Training volume and intensity both matter. A balanced diet that supplies B vitamins and other nutrients supports the process.
Do mitochondrial supplements work?
The evidence is limited. CoQ10, NAD+ precursors, alpha-lipoic acid and PQQ all have roles in energy metabolism, but human trials testing whether supplements improve mitochondrial function are small and short. Creatine has strong evidence for short-burst exercise performance, which is a different question.
Does mitochondrial function decline with age?
On average, yes. A study of 146 healthy adults found that mitochondrial DNA and ATP production in muscle declined with age. Exercise training has been shown to improve mitochondrial respiration in older adults.
Which foods support mitochondrial health?
No single food is proven to boost mitochondria. A varied diet supplies the B vitamins, such as niacin, that become the coenzymes mitochondria use. Animal foods such as beef, pork and salmon also contain creatine, about 2 g per pound.
Are mitochondrial supplements safe?
Most are well tolerated in trials. CoQ10 can cause mild digestive upset and may interact with warfarin and insulin. Creatine often causes water weight gain. Long-term safety data for NAD+ precursors and PQQ are limited. Check with your healthcare provider first, especially if you take medication.
Sources
- NIH Office of Dietary Supplements. Dietary Supplements for Exercise and Athletic Performance: Fact Sheet for Health Professionals.
- NIH Office of Dietary Supplements. Niacin: Fact Sheet for Health Professionals.
- National Center for Complementary and Integrative Health. Coenzyme Q10.
- MedlinePlus Genetics. Mitochondrial DNA. National Library of Medicine.
- Hernández-Camacho JD, Bernier M, López-Lluch G, Navas P. Coenzyme Q10 supplementation in aging and disease. Front Physiol. 2018.
- Granata C, Jamnick NA, Bishop DJ. Training-induced changes in mitochondrial content and respiratory function in human skeletal muscle. Sports Med. 2018.
- Robinson MM, Dasari S, Konopka AR, et al. Enhanced protein translation underlies improved metabolic and physical adaptations to different exercise training modes in young and old humans. Cell Metab. 2017.
- Short KR, Bigelow ML, Kahl J, et al. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci U S A. 2005.
- Elhassan YS, Kluckova K, Fletcher RS, et al. Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures. Cell Rep. 2019.
- Solmonson A, DeBerardinis RJ. Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem. 2018.
- Fogacci F, Rizzo M, Krogager C, et al. Safety evaluation of α-lipoic acid supplementation: a systematic review and meta-analysis of randomized placebo-controlled clinical studies. Antioxidants (Basel). 2020.
- Harris CB, Chowanadisai W, Mishchuk DO, et al. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013.
Disclosure: OPA Nutrition sells supplements, including products mentioned in this article. This content is for education only and is not medical advice. Statements about dietary supplements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. Talk to your healthcare provider before using any supplement, especially if you take medication or have a medical condition.
Written and reviewed by Michael Gonzales, Founder, OPA Nutrition · Last reviewed: · How OPA researches and writes
