A Guide to Mitochondrial Health Supplements
Mitochondria are cellular organelles (i.e., specialized cellular subunits) with vital roles in the cellular function and physiology of most living organisms. Among mitochondria’s many functions, one stands out because of how particularly indispensable it is: mitochondria are responsible for the conversion of energy extracted from foods into cellular energy, a process known as energy metabolism. Cellular energy takes the form of a molecule called adenosine triphosphate (ATP), often described as the energy currency of the cell [1].
Mitochondria are responsible for the conversion of energy extracted from foods into cellular energy, a process known as energy metabolism.
ATP is an energy-rich molecule that releases a large amount of energy when its chemical bonds are broken. This energy powers all the cellular processes that require energy input, including the synthesis of macromolecules such as DNA and proteins, cellular growth and assembly of cellular structures, skeletal and cardiac muscle contraction, neuronal firing, and many other processes. It’s estimated we make about our body weight in ATP every day. Because the vast majority of ATP is produced by mitochondria, they are known as “the powerhouse of the cell” [1].
But mitochondria have many other roles in processes that are also essential for cellular health, including the regulation of cell survival and cell death pathways, in redox homeostasis (i.e., the balance between oxidant and antioxidant processes) in heat generation (thermogenesis) in brown fat, and in immune function and signaling.
Figure 1. Mitochondria. Source: US National Human Genome Research Institute
How ATP is Produced in Mitochondria
ATP is generated from the metabolic breakdown of carbohydrates (glucose), fats (fatty acids), and, to a lesser extent, proteins (amino acids). The primary metabolic pathways of energy metabolism—glycolysis (which breaks down glucose) and fatty acid oxidation (which breaks down fats)—converge in a mitochondrial metabolic pathway called the citric acid cycle. In these pathways, sequential electron transfer reactions (redox reactions, from reduction, the gain of electrons, and oxidation, the loss of electrons) extract electrons from carbon units that form the backbone of glucose and fatty acids, leading to the production of carbon dioxide (CO2) as a byproduct.
These electrons are then transferred to electron carriers, the molecules nicotinamide adenine dinucleotide (NAD+, a coenzyme form of vitamin B3) and flavin adenine dinucleotide (FAD+; a coenzyme form of vitamin B2), reducing them to NADH and FADH2. These high-energy electrons then move from NADH and FADH2 to the electron transport chain in the inner mitochondrial membrane. The movement of electrons is coupled with the transfer of protons (H+) across the membrane to generate the mitochondrial membrane potential that drives ATP biosynthesis. This process of transferring electrons and pumping H+ is called oxidative phosphorylation (often shortened as OXPHOS). Oxygen is the final electron acceptor and is converted into water (H2O) with the addition of electrons and H+.
Figure 2: Electron transport chain. Source: OpenStax, Anatomy and Physiology; 24.2 Carbohydrate Metabolism. License CC BY 4.0
What is Mitochondrial Health?
Keeping mitochondria healthy is essential for optimal cell function and, consequently, for our health in general. Unfortunately, as we age, mitochondrial performance tends to decline, affecting the production of energy that our cells and tissues need to function optimally. Loss of mitochondrial function is actually one of the hallmarks of aging [2].
As we age, mitochondrial performance tends to decline, affecting the production of energy that our cells and tissues need to function optimally.
One of the factors that contribute to the loss of mitochondrial function with aging is oxidative stress. Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and the ability of our body’s antioxidant defense system to detoxify these molecules.
ROS are naturally produced in all cells. At low levels, they have important actions as signaling molecules that regulate cellular function and homeostasis. However, when they accumulate, ROS can damage mitochondria and other cellular structures and molecules, including DNA and proteins, and accelerate aging [3].
Mitochondria are actually the main site of ROS generation, as a byproduct of the electron transport chain. Oxygen, the final electron acceptor, does not always bind H+, which leads to the generation of ROS [3]. Mitochondrial ROS have a key role in linking mitochondrial metabolism and cell signaling pathways and, in healthy conditions, they’re kept in check by cellular antioxidant defenses [4].
But with aging, several age-related processes start to gradually impair mitochondrial function, such as an accumulation of mitochondrial DNA mutations and loss of mitochondrial quality control mechanisms, including mitophagy (a form of autophagy that removes damaged mitochondria) [5,6]. These changes compromise the efficiency of the electron transport chain and, among other consequences, enhance the production of ROS to a point that can overpower cellular antioxidant defenses and lead to oxidative stress. Because mitochondrial DNA is very susceptible to oxidative damage, this can further aggravate the loss of mitochondrial function and compromise cell energy production [7].
Figure 3. Mitochondrial ROS production in the electron transport chain. Source: Tirichen et al. Front Physiol, 2021. License CC BY 4.0
How Can I Support My Mitochondrial Health?
There are several simple lifestyle choices that can help to support mitochondrial function.
Healthy Diet
One of the ways to support mitochondrial health is by eating a healthy diet with plenty of fruits and vegetables rich in polyphenols. Polyphenols are a family of natural compounds found abundantly in plants. Many polyphenols are plant pigments that protect plants from environmental stressors, which is why they’re often found in the highest amounts in the skins or peels of fruits and vegetables, giving them their characteristic colors.
One of the ways to support mitochondrial health is by eating a healthy diet with plenty of fruits and vegetables rich in polyphenols.
In the human body, dietary polyphenols can also support protection from stressors, including antioxidant defenses [8]. Polyphenols have the ability to enhance antioxidant defenses by promoting the expression and /or activity of enzymes that remove ROS or synthesize cellular antioxidants [9], which helps to protect mitochondria from oxidative stress. Based on findings from preclinical research, some particular polyphenols may also support mitochondrial function by enhancing the efficacy of cell energy pathways and other mitochondrial processes and promoting mitochondrial biogenesis (i.e., the generation of new mitochondria) [9].
For example, cocoa, which is rich in polyphenols, may support mitochondrial structure and function, promote mitochondrial biogenesis, and support mitochondrial metabolic pathways, including fatty acid oxidation, the citric acid cycle, and the electron transport chain and ATP production [10–19].*
Similarly, pomegranate, a fruit rich in polyphenols, may support mitochondrial function by promoting mitochondrial antioxidant defenses, electron transport chain function and ATP production, mitochondrial biogenesis, and mitophagy [20–26].*
Another example is resveratrol, a polyphenol found in high amounts in the skins of grapes and berries, for example. Resveratrol may support healthy mitochondrial structure and function by promoting mitochondrial biogenesis, energy metabolism, and supporting a healthy NAD+ pool [27–34].*
Apigenin is a flavonoid polyphenol found in many fruits and vegetables, including celery and parsley, and present in very high amounts in the flowers used to make chamomile tea. Apigenin may promote mitochondrial biogenesis, support citric acid cycle function, electron transport chain and ATP production, and NAD+ levels [35–39].*
Rutin is a flavonoid glycoside composed of the flavonoid quercetin and the disaccharide rutinose. Foods with the highest concentrations of rutin include capers, black olives, buckwheat, and asparagus, although it's found in a wide variety of plants. Rutin may support healthy mitochondrial function and promote mitochondrial biogenesis [40–46]. Quercetin, the flavonoid that is part of rutin’s structure, may also support mitophagy [47–50].*
Exercise
Exercise requires great amounts of ATP to power muscle contraction. The huge expenditure of ATP reduces its availability in cells, which activates energy sensors that stimulate adaptive metabolic stress responses. AMP-activated protein kinase (AMPK) is a signaling molecule that is activated in response to an increased AMP/ATP ratio (i.e., when ATP levels drop and more AMP is available relative to ATP). So, when ATP is being consumed at a high rate, AMPK becomes more active, acting as an ATP sensor that signals the cell energy status of the cell [51]. AMPK promotes the activity of a molecule called PGC-1α, regarded as the master regulator of mitochondrial biogenesis because it can drive virtually all aspects of mitochondrial biogenesis [52]. Therefore, through AMPK and PGC-1α signaling, muscle cells can respond to exercise by producing more mitochondria and more mitochondrial enzymes.
Endurance training, resistance training, yoga, and HIIT have all been shown to support mitochondrial function and biogenesis.
Different forms of exercise have been shown to support mitochondrial function and biogenesis in both young and older adults, including endurance training (e.g., running, biking, walking), resistance training (e.g., weight lifting), and HIIT [53–57]. But don’t overdo it: too much exercise may actually disrupt metabolic homeostasis and lead to a decline in mitochondrial function [56]. The goal is to keep exercise in the hormetic range.
Even milder forms of exercise support mitochondrial health. A recent study in individuals with immune dysfunction (known to influence mitochondrial health) studied the effects of yoga on mitochondrial function. Just 8 weeks of yoga practice (120 min sessions, five times a week) that included asanas (physical postures), pranayama (breathing techniques), and dhyana (meditation), improved markers of mitochondrial health.
Heat Exposure
During intense exercise, muscle temperature increases. This heat stress may contribute to the beneficial actions of exercise in mitochondria by promoting adaptive stress responses [58,59]. Low levels of heat stress applied passively to skeletal muscle (i.e., without muscle contraction) have been shown to stimulate increases in mitochondrial enzyme content and respiratory capacity [60–62].
Passive heat exposure in saunas or through immersion in hot water may support skeletal muscle metabolism and mitochondrial function.
Therefore, passive heat exposure in saunas or through immersion in hot water may support skeletal muscle metabolism and mitochondrial function. One study in humans showed that a single session of whole-body heating using a water-perfused suit, which raised internal muscle temperature to approximately 39 °C, increased signaling for mitochondrial biogenesis [63].
Cold Exposure
Similarly to heat, cold exposure can promote adaptive stress responses that support mitochondrial function. Cold therapy increases cellular energy demand to generate heat to keep us warm, which can trigger metabolic adaptations. Studies have shown that cold exposure increases PGC-1α expression in skeletal muscle and adipose tissue, indicating that it may support mitochondrial biogenesis [64,65].
Cold exposure can promote adaptive stress responses that support mitochondrial function.
Brown adipose tissue (BAT) is a type of adipose tissue specialized in generating heat (thermogenesis) [66]. During cold exposure, BAT undergoes remodeling to increase its thermogenic potential. Repeated cold exposure causes increased mitochondrial activity in BAT to generate heat [66], which can lead to metabolic adaptations, including an enhancement of mitochondrial function and biogenesis [67,68]. But again, too much cold can be detrimental because it can increase the production of damaging ROS by mitochondria [69].
Mitochondrial Supplements
An additional strategy to support mitochondrial function is through dietary supplements. Supporting mitochondrial health was one of our main goals when we developed Qualia Life. We included a selection of complementary ingredients that may promote healthy mitochondrial function by supporting mitochondrial energy metabolism, proper electron transport chain function, balanced ROS production, mitochondrial antioxidant defenses to help keep ROS in check, mitophagy to help remove damaged mitochondria, and mitochondrial biogenesis to help cells generate new mitochondria and maintain a healthy mitochondrial network.* Those ingredients include the polyphenols mentioned above, but also compounds that have a direct role in mitochondrial function, such as those described below.
Common Mitochondrial Health Supplements
Magnesium
Magnesium (Mg2+) is an essential mineral with key functions in human physiology. Magnesium is involved in most, if not all, major metabolic processes within cells, including cell energy metabolism. Magnesium is required for the activity of all enzymes that use and many that synthesize ATP [70,71]. Importantly, ATP itself must bind to a magnesium ion to be biologically active [72]. Consequently, magnesium availability is paramount for the efficiency of mitochondrial cell energy generation and for the viability of all cellular activities that require ATP [73].*
Coenzyme Q10
Coenzyme Q10 (CoQ10) is essential for ATP production in mitochondria. CoQ10 is part of the electron transport chain, where it transfers electrons by undergoing redox cycles between its three redox states (ubiquinone [fully oxidized], ubisemiquinone, and ubiquinol [fully reduced]). By supporting electron transport chain performance and ATP production, CoQ10 also helps to maintain an adequate NAD+ pool (NAD+/NADH ratio) and mitochondrial membrane potential, which are essential for mitochondrial and cellular function. CoQ10 also supports antioxidant defenses, helping protect membranes from oxidative stress, including mitochondrial membranes. CoQ10 has also been shown to support mitochondrial biogenesis [74–79].*
Alpha-lipoic acid
Alpha-lipoic acid (or R-lipoic acid) is an important mitochondrial compound because it’s used in enzymes for the metabolic processes that produce ATP. Alpha-lipoic acid is a cofactor for the enzyme pyruvate dehydrogenase, which converts the final product of glycolysis, pyruvate, to acetyl-CoA, which then enters the citric acid cycle. It is also a cofactor for alpha-ketoglutarate dehydrogenase, which is part of the citric acid cycle and a key control point in this pathway [80]. By supporting these enzymes, alpha-lipoic acid helps to maintain the flow of energy metabolism, contributing to healthy mitochondrial function. Accordingly, alpha-lipoic acid has been shown to support the electron transport chain, oxidative phosphorylation, and ATP production, [81–84], helping to maintain the NAD+ pool and the NAD+/NADH ratio [85,86]. It also supports mitochondrial biogenesis [81,83,85,87,88].*
L-Carnitine
L-carnitine is an important molecule because it’s needed to convert fat into energy in mitochondria. L-carnitine is used to transport long-chain fatty acids across the mitochondrial membrane for breakdown by mitochondrial fatty acid oxidation. This function allows dietary fats to be used for energy production and enhances mitochondrial potential to burn fat to produce ATP [89]. This function is especially important in tissues and organs that use a lot of fat as an energy source, including the heart and skeletal muscles. Its actions help to maintain mitochondrial function and structure [90,91].*
Vitamin B3 — Niacin and Niacinamide
Niacin (nicotinic acid) and niacinamide (nicotinamide) are precursors for NAD+, which is one of the carriers that transport electrons to the electron transport chain to produce ATP. By supporting the synthesis of NAD+ through different pathways, niacin and niacinamide help to maintain an adequate pool of NAD+, which is essential for the extraction of energy from sugars and fats and for healthy mitochondrial function [92].*
Vitamin B2 — Riboflavin
Riboflavin is a precursor for FAD+, which is the other carrier that transports electrons to the electron transport chain to produce ATP. Similarly to NAD+, supporting FAD+ production helps to maintain healthy cell energy metabolism and ATP production [92].*
Learn more about Qualia supplements here.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
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