10 Best Supplements for Mitochondrial Health of 2024

Mitochondria play a critical role in the production of necessary energy for the cell's survival and functioning. They are responsible for most of the useful energy obtained from the breakdown of carbohydrates and fatty acids.

Many chronic diseases can be traced to mitochondrial dysfunction. Seemingly diverse conditions—including diabetes, hypertension, heart disease, cancer, allergies, autoimmune diseases such as rheumatoid arthritis, and even various mental illnesses—can be understood through a “unified theory” of mitochondrial imbalance.

However to simplify things let’s talk about energy and longevity which is what their function translates to for practical purposes. And to help this occur, we can review the health practices, along with the best supplements to improve mitochondrial function.

Mitochondrial Dysfunction and Aging

Many studies found that age-related processes are associated with mitochondrial dysfunction.

Mitochondrial dysfunction, characterized by a loss of efficiency in the synthesis of ATP, is a characteristic of aging and, essentially, of all chronic diseases. Loss of function in mitochondria can result in excess fatigue and even other symptoms in just about every chronic disease you can imagine. These conditions include neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, and Amyotrophic Lateral Sclerosis.

Metabolic syndrome, heart disease, and diabetes are all associated with mitochondrial dysfunction. Metabolic syndrome is a group of conditions that combine hypertension, hyperglycemia, abdominal obesity, and abnormal cholesterol or triglyceride levels. Metabolic syndrome greatly increases the risk of cardiovascular disease, stroke, and Type two diabetes. There are numerous reports mentioning mitochondrial dysfunction and lower oxidative capacity in patients with Type two diabetes compared with healthy individuals.

The cardiovascular system strongly depends on mitochondrial function. Cardiomyocytes (heart cells) have very high mitochondrial content in order to produce the necessary ATP, and mitochondrial dysfunction inevitably leads to the development of cardiovascular diseases.

There is now increasing evidence of mitochondrial dysfunction in Alzheimer’s Disease, Parkinson’s Disease, Huntington’s disease, and Amyotrophic lateral sclerosis. Even some psychiatric conditions, such as autism spectrum disorders, schizophrenia, and bipolar mood disorders, are included.

A number of age-related processes (e.g., “normal aging of the brain”) are associated with mitochondrial dysfunction, so most of the popular aging theories take this into account. The mitochondrial theory of aging posits that the accumulation of damage to mitochondria DNA promotes the process of cellular aging of both humans and animals. The theory claims that there is a vicious cycle involving the accumulation of damage in mitochondrial DNA, which then leads to more oxidative damage due to defects in the mitochondrial respiratory chain.

In addition, mitochondrial dysfunction plays a significant role in the inflammatory response in acute human pathologies. Systemic Inflammatory Response Syndrome (SIRS) is a pathological state with a systemic immune reaction to severe damage, including ischemia, acute pancreatitis, trauma, and sepsis.

Autoimmune diseases such as rheumatoid arthritis, Crohn’s disease, and systemic lupus erythematosus are all characterized by mitochondrial failure. Of course, truly fatiguing illnesses, such as CIRS (mycotoxin and mold illness and Chronic Lyme), Chronic fatigue syndrome, fibromyalgia, and Gulf War Syndrome have mitochondrial near-failure as a prominent component. Lastly, as you might predict, cancer and chronic infections round out the list of disorders. If you have any one of these disorders, you will need to improve your mitochondrial health and function in order to recover.

A study observing mitochondrial dysfunction in the elderly supports the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly. Furthermore, it is also known that mitochondrial mutations increase in frequency with age in both animal models and in humans.

Best Supplements for Mitochondrial Health

1. CoQ10

CoQ10, also known as coenzyme Q10, is one of the most popular dietary supplements for heart health and overall wellness. 

A study showed that ubiquinol-10 may enhance mitochondrial activity by increasing levels of SIRT1, PGC-1α, and SIRT3 that slow the rate of age-related hearing loss and protect against the progression of aging and symptoms of age-related diseases.

In studies using Alzheimer’s disease models, CoQ10 administration significantly delays brain atrophy and characteristic β-amyloid plaquing. In a 4 month clinical study on around 100 Alzheimer’s patients who took an oral mixture of vitamins E, C, CoQ10, and α-lipoic acid, the group receiving supplementation showed significant reductions in oxidative stress markers and subsequent DNA damage.

Individuals with Parkinson’s disease tend to show increased levels of oxidized (and by definition: damaged) CoQ10. They also have significant increases in markers of oxidative stress and damage in their brains, which is partially reversible with CoQ10 administration.

One last important clinical note: recall that the heart is filled with mitochondria which are partially powered by CoQ10. If you are taking a statin drug, please be aware that they deplete your body of CoQ10, so supplementation is a must.

CoQ10 Recommended Dosage

CoQ10 dosages of 90 to 200 mg per day are often advised, while larger doses of 300 to 600 mg may be necessary for specific illnesses. CoQ10 is a supplement is generally well-tolerated and safe.

2. Pyrroloquinoline Quinone (PQQ)

Pyrroloquinoline quinone (PQQ) also called methoxatin is contained in fruits and vegetables such as kiwi fruit and green peppers. It has received a lot of research attention in the past several years. PQQ can reduce reactive oxygen species (ROS) levels and improve the apoptosis (death) of tumor cells. PQQ protects tissues by regulating the redox (electron transfer) reaction. Moreover, PQQ protects overall tissue function by improving the mitochondrial function of the liver, neurons, and other important tissues. It can also reduce atrophy in mouse skeletal muscles.

PQQ decreases oxidative stress (production of ROS) and inflammation which, by definition, will protect mitochondria. It also increases mitochondrial biogenesis, which is the formation of new, young-acting mitochondria. It is neuroprotective, too. Here’s how. Recall that you have read about GABA versus glutamate or inhibitory (relaxing) versus excitatory (too stimulating) neurotransmitter activity. We want more GABA than glutamate, plain and simple. Too much glutamate damages brain cells. PQQ protects neurons by preventing the long-term over-activation of the glutamate (NMDA) receptors, which results in toxic excitotoxicity of neurons. This over-stimulation of brain cells is associated with many neurodegenerative diseases and seizure disorders.

Recall again that you have the largest concentration of mitochondria in your brain, heart, and skeletal muscles. The brain “wins” pound for pound by a little edge, which is why you feel tired after using your brain all day. With this in mind, remember that when we protect the brain, we’re protecting brain mitochondria. PQQ protects the brain (to a certain extent) against neurotoxicity induced by mercury and other potent toxins such as mold mycotoxins. Lastly, it too helps to prevent the accumulation of amyloid tau and beta proteins associated with Parkinson’s and Alzheimer’s diseases.

3. Acetyl-L-Carnitine for Mitochondrial Health

Acetyl-l-carnitine is a naturally occurring fatty acid transporting amino acids. L-carnitine supplementation has long been studied and then used in many mitochondrial dysfunction disorders. These disorders are also characterized by low concentrations of serum l-carnitine levels such as heart disease, diabetes, kidney disease, and overwhelming infections.

An important cellular longevity function of l-carnitine has been to increase the rate of mitochondrial oxidative phosphorylation (ATP production) that declines with age. A study where old rats were fed acetyl-l-carnitine resulted in the reversal of age-related decreases in l-carnitine levels, an increase in fatty acid metabolism, and an increase in mitochondrial activity. Acetyl-l-carnitine also reverses the age-related decline in muscle mitochondria.

Clinical studies show that L-carnitine supplementation may also be useful in alleviating fatigue symptoms in hypothyroid patients, especially in those younger than 50 years and those who have hypothyroidism after thyroidectomy for thyroid cancer. Note: L-carnitine is the nomenclature used for many clinical studies, but due to l-carnitine’s ability to increase TMAO, experts suggest that all human supplementation be done with acetyl-l-carnitine.

4. NAD Boosting Supplements

NAD is now the big news, thanks largely to the research by Dr. David Sinclair and his best-selling book, “Lifespan.” Recall the mentions throughout this article about the conversion of NAD+ to NADH, and vice versa, as essential reactions in creating ATP. Recall that ATP is cranked out by mitochondria, and gives cells (and you) energy. Therefore NAD and its substrates are crucial for cellular energy, mitochondrial biogenesis and it turns out; cellular longevity. All that remains to be seen, is proof positive that one “form” of NAD is superior to another. Here are some of the data.

Oral NADH supplementation can reduce symptoms in patients with chronic fatigue. One study on patients with chronic fatigue syndrome treated participants with micro-encapsulated, oral NADH or a placebo for a month’s time. 8 of 26 study participants (about 1/3) responded positively with increased well-being and energy levels to the NADH compared with 2 of 26 (8%) in the placebo group.

This supplement also shows promise for neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases. The increase in measured NADPH levels correlates with a marker for aging: an increase in telomere length.

NAD will stimulate the SIRT1 pathway which is notably dysfunctional in those with metabolic syndrome, diabetes, and more. When you stimulate the SIRT1 pathway, you lower leptin levels, making it again possible to lose weight, improve blood sugar, cholesterol, and triglyceride levels, and in fact, all aspects of metabolic syndrome.

Taken orally, NMN (nicotinamide mononucleotide) is rapidly absorbed and converted to NAD+. In numerous studies, supplementation with NMN increases NAD+ biosynthesis, suppresses age-related fatty tissue inflammation, enhances insulin secretion and its action, improves overall mitochondrial function, and in the brain, it improves mitochondrial as well as neuronal function. In animal studies, it extends lifespan. In fact, NMN given to mice does quite a bit. Before I discuss NMN, let me give a shoutout to nicotinamide riboside- also converted to NAD+. As well as NMN? We don’t know, and the research continues. Meanwhile, we have a lot of data from mice studies.

Orally administered NMN is rapidly converted to NAD+ in mice. NMN has been shown to enhance energy metabolism and physical activity, suppress age-associated weight gain, improve insulin sensitivity and even improve ocular function. It improves mitochondrial metabolism and prevents age-related negative changes in gene expression. In mice bred to be obese or diabetic, NMN improved both the action and secretion of insulin.

NMN also protects the mouse heart from ischemia and/or reperfusion injury. It restores skeletal muscle mass in aging mice. Of special interest to those of us who treat many patients with brain issues, it has been shown to slow cognitive decline in a mouse model of Alzheimer’s disease, by improving the survival of neurons, improving energy metabolism, and reducing oxidative stress. It may also help maintain the integrity of the blood-brain barrier.

NMN also probably suppresses the increase in systemic inflammation associated with aging based on the studies which show that it lowers adipose tissue inflammation associated with age. In fact, surprisingly enough, older mice appear to be more responsive to NMN, in comparison with younger mice.

Some studies appear to suggest an increase in blood vessel formation called angiogenesis with artificially increased NAD levels for prolonged periods of time. This is why, despite the fact that I use a lot of NMN and intra-nasal NAD in my clinical practice, I have patients take intermittent breaks from it, and will do so until more data is available on this phenomenon.

Nicotinamide Riboside

Nicotinamide Riboside (NR) is a precursor of NAD+, and its supplementation is known to improve mitochondrial function. In a recent twin study, twenty pairs of monozygotic twins with differing body mass indexes were given increasing amounts of NR over five months. The authors found that supplementation led to enhancements in overall NAD+ metabolism, increased muscle mitochondria count, better myoblast differentiation, and improved gut microbiota balance in both twins of each pair [49]. Other studies have also found that NAD+ and NR play a vital role in improving mitochondrial function. 

5. Melatonin

Endogenously produced melatonin diminishes during aging, further increasing oxidative damage to mitochondrial components. More normal mitochondrial physiology is preserved in aging neurons with melatonin supplementation. (Ageing Research Reviews 2024)

Melatonin is a potent antioxidant that counters free radicals and ROS generated during cellular metabolism [25]. It protects mitochondria by neutralizing ROS, hindering the opening of the mitochondrial permeability transition pore, and activating uncoupling proteins [57]. Consequently, melatonin sustains the optimal membrane potential of mitochondria, ensuring their functions remain intact. Furthermore, melatonin governs the creation and movement of mitochondria. It frequently curtails the division of mitochondria while fostering their fusion. The rhythmic oscillation in mitochondrial dynamics mirrors melatonin's natural secretion cycle, observed particularly in pineal cells and likely in other cell types [58]. Recent studies also highlight melatonin's role in promoting mitophagy and enhancing mitochondrial equilibrium [58]. 

Mitochondrial melatonin production is one of the reasons why regular sun exposure is so crucial. Most people understand that sun exposure on bare skin generates vitamin D, courtesy of UVB (ultraviolet B radiation). Few, however, understand that the near-infrared spectrum, when hitting your skin, triggers the generation of melatonin in your mitochondria. 

Anytime your skin is exposed to natural sunlight, however, you can be sure you’re receiving the necessary wavelengths of near-infrared to generate melatonin in your mitochondria. Conversely, when indoors under artificial lighting, you can be certain you’re not getting any. This is because most window glass is low-e and filters out a good portion of the near-infrared, so even sitting near a window is not going to provide you with this benefit.

There are two types of melatonin in your body: The melatonin produced in your pineal gland, which traverses into your blood, and subcellular melatonin produced inside your mitochondria.

Importantly, the melatonin that your mitochondria produces does not escape your mitochondria. It doesn't go into your blood. So, you're not going to directly increase your blood or serum level of melatonin by sun exposure. But, bright sun exposure around solar noon will indirectly help your pineal gland to produce melatonin during the night.

It is important to understand that your blood level of melatonin is indicative of the melatonin produced in your pineal gland, and/or oral supplementation. Conversely, the melatonin produced by your pineal gland cannot enter into the mitochondria, which is why it is so important to get regular sun exposure.

Oral supplementation, however, can enter your cells and mitochondria. 

If you supplement with melatonin, it can also enter cells and get into the mitochondria as well. And that is also very important ... As you age, mitochondrial melatonin diminishes. If you supplement with melatonin, it will get into your mitochondria and, in fact, do what melatonin does — neutralize free radicals and protect the mitochondria's function.

6. Curcumin

Curcumin is the most commonly found in turmeric and has antioxidant activities [50]. Studies have shown that curcumin can boost mitochondrial fusion activity, decrease mitochondrial fission mechanisms, and elevate mitochondrial biogenesis. Treatment with curcumin has demonstrated enhanced mitochondrial function and cell viability [50]. Curcumin potentially enhances mitochondrial potential and ATP levels and might also contribute to restoring mitochondrial fusion, likely through the up-regulation of PGC-1α protein expression [50].

A 2022 systematic review showed that curcumin helped improve metabolic syndrome objectively (reducing BMI, triglycerides, total cholesterol, and insulin resistance).

7. Vitamin C

Vitamin C is an essential nutrient for humans due to their inability to synthesize it from glucose [59]. It holds the capacity to enhance mitochondrial functioning. Its supplementation can mitigate excessive ROS production, safeguarding mitochondria and reducing inflammation across tissues, including skeletal muscle [59,60]. Consequently, it shows promise in enhancing recovery and athletic performance. However, the impact of antioxidant supplementation on skeletal muscle adaptation to exercise remains uncertain. While it might interfere with hormesis, where stress-induced ROS signal beneficial adaptations, it could also potentially prevent prolonged elevation of ROS caused by excessive exercise stress, leading to impaired function and damage [58-60].

8. Resveratrol

Resveratrol is a polyphenolic phytoalexin in grapes, berries, peanuts, and wines [51]. It is recognized for its antioxidant, anti-inflammatory, anti-apoptotic, and anticancer properties [52]. Studies have found that resveratrol regulates mitochondrial function, redox processes, and dynamics. Additionally, resveratrol reduces mitochondrial damage caused by specific stressors [53]. For instance, it increases the presence of antioxidant enzymes within mitochondria, consequently reducing reactive species production by these structures [52,54]. Furthermore, resveratrol initiates mitochondrial growth, leading to improvements in the bioenergetic status associated with mitochondria in mammalian cells [51,52,54].

9. D-ribose

We know that D-ribose has documented positive mitochondrial effects for those who are genetically d-ribose deficient. It’s a popular bodybuilding supplement which “hardcore” bodybuilders credit as being helpful with their muscular fatigue. Studies have looked at neurodegenerative diseases such as Multiple Sclerosis and ALS with promising results. (source)

10. Phospholipids

Mixtures of probiotic, phospholipid, and antioxidant preparations have shown some clinical promise in fatiguing illness. This mixture is made using antioxidant powders, probiotics, and phosphatidylserine. The bulk of the studies have been with patients who have fibromyalgia and/or chronic fatigue syndrome (CFIDS).

Other Best Natural Ways to Vitalize Mitochondrial Health

It is vital to keep your mitochondria hale and hearty to have a healthy lifestyle. There are many natural ways to boost mitochondrial function, ten of which are listed below:

Cut Excess Calories From Your Diet

Obesity and heightened inflammatory processes are caused by an excess of calories, which increases reactive oxygen species (ROS) generation during the Krebs cycle in mitochondria. 

Increased amounts of ROS cause cellular damage known as oxidative stress which has been associated to many diseased (i.e., Parkinson's disease, Alzheimer's disease (AD), and many more)

According to some datas, caloric restriction attenuates age-related cellular oxidative damage, decreases mitochondrial oxidant emission, and increases the activity of endogenous antioxidants.

Calorie Restriction (CR) has been shown to increase mitochondrial biogenesis by 30% in a landmark study on male mice. The study found that implementing CR for durations of either 3 or 12 months triggered the expression of endothelial nitric oxide synthase and the formation of 3',5'-cyclic guanosine monophosphate in different tissues of male mice. This was accompanied by the generation of new mitochondria, leading to escalated oxygen consumption and ATP production. The study strongly provided proof that CR is responsible for increasing mitochondrial function [42]. Other studies have also found similar results in cell lines and animal models that CR induced the proliferation of the mitochondria via a signaling pathway involving peroxisome proliferation-activated receptor coactivator 1α [43].

Eating an Anti-inflammatory Diet

According to research, inflammatory foods stress and overwork the mitochondria, therefore avoiding them may help your body stay healthy and powerful.

Physical Activity Daily

Physical activity is the most effective strategy to boost your oxygen intake, which is essential for the Krebs cycle in mitochondria. As your body expends more energy, it will be forced to manufacture more mitochondria to meet the need. Your body and mitochondria will become complacent if you are not expending energy or using up oxygen.

Exercise plays a vital role in regulating mitochondrial functions. Studies have found that 30 minutes of daily exercise reduces mitophagy and increases longevity. A systematic review found that regular aerobic exercise enhanced mitochondrial morphology, biogenesis, dynamics, oxidative, and antioxidant capacity [55]. Thus, exercise remains our best behavioral medicine for improving mitochondrial health and individual longevity [56].

Get Enough Sleep

Sleep can affect mitochondrial function and thus our health and longevity. There's a connection between having a shorter lifespan and having fewer copies of mitochondrial DNA in the blood. A study found that people who did not sleep enough, and had a restless sleep, also had the lowest copies of mitochondrial DNA. (Source)

Yoga 

A randomized controlled trial observing the impact of yoga in rheumatoid arthritis patients suggest that yoga enhance mitochondrial health, improve circadian rhythm markers, OS marker regulation, upregulation of transcripts that maintain mitochondrial integrity, reduce disease activity and its associated consequences on health outcome and hence can be beneficial as an adjunct therapy.

Yoga enhances the integrity of the mitochondria by modifying the expression of transcripts responsible for maintaining mitochondrial integrity [39]. This adjustment contributes to maintaining balanced free radical levels, a pivotal factor for elevating mitochondrial copy numbers. Moreover, it enhances cytochrome c oxidase (COX-II) activity, boosts nicotinamide adenine dinucleotide (NAD+) levels, optimizes markers of oxidative stress, and raises the levels of transcripts vital for preserving mitochondrial integrity [39,40]. Consequently, it diminishes the impact of disease activity on physical and mental well-being. As a result, yoga holds promise as a supplementary therapeutic approach in mitochondrial dysfunction [39-41].

Intermittent Fasting

Intermittent Fasting’s (IF) role in improving mitochondrial function is known. A study found enhanced oxygen flow and ATP production through better mitochondrial respiration, demonstrated by strong respiratory control ratios in rats following IF for eight weeks with alternate day fasting (ADF) [44,45]. Another study observed reduced heart inflammation and oxidative stress, similar to younger rats following a 24-month ADF plan [44,45]. Combining ADF IF with intense intermittent exercise also improved metabolic pathways, significantly lowering malondialdehyde levels and plasma protein oxidation [45].

Methylene Blue

Methylene Blue’s role in regulating mitochondrial function is well-documented [7]. Research has shown that methylene blue’s unique ability to redirect electrons within the mitochondrial electron transfer chain directly, from NADH to cytochrome c, results in increased complex IV activity, thereby boosting mitochondrial function and reducing oxidative stress [46,47]. These remarkable properties aid in curbing cell damage and enhancing cellular metabolism through mitochondrial improvements. Consequently, the impressive mitochondrial response of methylene blue has paved the way for exploring its potential applications in addressing conditions linked to mitochondrial dysfunction, including age-related issues affecting various tissues like the brain and skin [46-48].

Final words

In any good health regimen, you want to eat an anti-inflammatory diet and take a few supplements. It makes sense to take vitamin D3 and K2 and high antioxidant power supplements for many reasons, including mitochondrial health. At this juncture, if you are healthy and have specific goals in mind, you might choose, let’s say, some acetyl-n-carnitine if you are lifting weights, or some PQQ if you have a family history of neurodegenerative disease. And currently, if you have metabolic syndrome, SIRT pathway issues, or fatiguing illness, it seems prudent and helpful to take NMN or other NAD boosting supplements e.g. Nicotinamide Riboside or Niacinamide.

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Best Supplements for Mitochondrial Health - Online Buying Guide

1. Life Extension Super Ubiquinol CoQ10 with PQQ: BUY ON AMAZON

2. Jarrow Formulas Co-Q10 100 mg: BUY ON AMAZON

3. Actif Super Ubiquinol CoQ10 with Enhanced Mitochondrial Support: BUY ON AMAZON

4. Doctor's Best Coq10, L-Carnitine, Magnesium: BUY ON AMAZON

5. Double Wood Supplements PQQ Supplement 20mg: BUY ON AMAZON

6. Mitochondria Maximizer with CoQ10 and Active PQQ: BUY ON AMAZON

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