12 Best Supplements for Mitochondrial Health (2025)

By Editorial Team - April 29, 2025

In this mitochondrial and cellular health series, we take a look at mitochondrial and cellular health—and review the research behind them.

The common denominator for overall health—including longevity, brain health, gut health, liver health, immune health, and kidney health—is mitochondrial health.

Mitochondria are involved in many vital processes in human cells, including energy production, fatty-acid oxidation, and the Tricarboxylic Acid (TCA) cycle, calcium signaling, apoptosis (cellular death), and heat production. 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 health.

Mitochondria and the Unified Theory of Cellular Health
Best Mitochondrial Support Supplements

CoQ10
PQQ
L-carnitine
NAD Boosting Supplements and B vitamins
Vitamin D3 and K2
Glycine and NAC
Magnesium and Molecular Hydrogen
Melatonin
D-ribose
Phospholipids
Miscellaneous supplements

What happens when mitochondria malfunction?
What about mitochondrial function and aging in general?
Mitochondria boosting health practices
Mitochondrial specific exercise
Final words

Mitochondria and The Unified Theory of Cellular Health

As you age, your mitochondrial function typically decreases, and this is a hallmark of both the aging process itself as well as most chronic disease. 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.

Proper mitochondrial functioning is crucial for every nucleated cell in a body. A number of diseases are characterized by dysfunction of muscular or neural systems or metabolic reactions. All these diseases and pathophysiological conditions are developed against a specific genetic background, together with environmental factors.

Mitochondria produce energy as ATP (adenosine triphosphate), which your body then uses to fuel your daily activities. Some cells have more mitochondria than others. Your brain, muscles, and heart cells are full of mitochondria. Putting diseases and aging to the side: you want your mitochondria working at full strength to keep your energy levels up, your brain sharp, and your muscles and heart at their peak performance.

The creation of new mitochondria (mitochondrial biogenesis) is needed for optimal aging, which we now call our healthspan. Not to be repetitive, but always remember this is mandatory to keep your energy levels at a peak. It’s also a part of what’s needed to protect you from oxidative stress.

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.

Best supplements to improve Mitochondrial Function

I see people perk right up within (literally) 24 hours of proper mitochondrial supplementation. If someone has a chronic and/or fatiguing illness or are just suffering from age-related mitochondrial failure, supplementation absolutely works. It sure beats energy drinks which end up causing adrenal issues and potentiating energy problems.

Here are the mitochondrial supplements that have been studied and proven effective.

1. CoQ10

CoQ10 is an essential electron carrier in the mitochondrial respiratory chain. In other (more complex) words, CoQ10 passes electrons between NADH-ubiquinone oxidoreductase, succinate-ubiquinone oxidoreductase, or succinate-cytochrome C oxidoreductase.

Basically, CoQ10 can be found in both oxidized (ubiquinone) and reduced (ubiquinol) forms, and the conversion between these oxidized and reduced states allows it to act as a cofactor of enzymatic reactions via the transfer of electrons.

CoQ10 is a critical part of the mitochondrial oxidative phosphorylation system. Over ten well-done studies show that supplementation with this vitamin-like antioxidant compound in individuals with reduced CoQ10 levels results in increased energy production and reduced fatigue. The most dramatic results are in those individuals with degenerative diseases.

Ubiquinone, also known as Coenzyme Q10, is an important cofactor in the mitochondrial electron transport chain and a potent antioxidant. Both ubiquinol and ubiquinone are forms of CoQ10 (coenzyme Q10).

Levels of CoQ10 in the heart can decrease with age, statin use, or due to genetic factors.

Some studies have shown that CoQ10 supplementation can improve mitochondrial respiratory function and reduce oxidative stress (Nature 2019, CASI 2022)

In patients with heart failure, CoQ10 treatment has been shown to significantly reduce major adverse cardiovascular events20 and lower the death rate. (source)

Here are some examples.

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.

Dosage: If you’re new to CoQ10 supplementation, an initial dose of 200 to 300 mg per day is recommended. After about three weeks, when plasma levels typically reach their optimal plateau, you can transition to a maintenance dose of 100 mg daily, which is sufficient for most healthy individuals.

2. PQQ

Pyrroloquinoline quinone (PQQ) 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. NAD and B Vitamins

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.

Dr. Frank Shallenberger, author of “Bursting With Energy: The Breakthrough Method to Renew Youthful Energy and Restore Health,” explains:

“B vitamins are absolutely critical for mitochondrial function — especially niacin, riboflavin and folate. Orally speaking, with niacin, I typically start them at 100 to 200 milligrams a day [but] you can go up to 2,000 mg easy on some patients. I use a B complex because I like to balance it out, but I'm focusing primarily on niacin, folate and riboflavin.”

Typically, when a deficiency of B vitamins is the cause of decreased mitochondrial function, I will see improved readings within two to three weeks, although the level of improvement can vary tremendously from one person to the next. An important caveat here is that mitochondria are vulnerable to any number of assaults, including emotional stress.

“I have literally seen patients have great mitochondrial function, be under stress for two months, and have their mitochondria wiped out just from emotional stress,” he says. “I haven't done the studies, but I'm pretty sure that if you get under a lot of emotional stress, I bet your mitochondria suffer a measurable hit within 48 hours.”

Vitamin B12

Vitamin B12 is needed to form red blood cells and DNA. It is also a key player in the function and development of brain and nerve cells. However, we believe the most important function it provides is methylation. If you don’t know what methylation is, allow us to briefly explain. Methylation is a biochemical process which is involved in a wide range of bodily functions, and is essential to our overall well-being. When methylation is out of balance, many different health problems may arise.

4. Acetyl-l-carnitine

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.

5. Vitamin D3 and K2

Vitamin D3

Decreased vitamin D levels reduce mitochondrial activity and ATP production from oxidative phosphorylation and increase oxidative stress and inflammation [205, 206]. Vitamin D–controlled mitochondrial health may also have implications for self-renewal capacity of cells [207].

Vitamin D is an important substance for skeletal muscle and bone support in humans. The regeneration of muscle includes complex mechanisms comprising the restoration of mitochondrial functions [207]. More specifically, vitamin D3 therapy increased mitochondrial oxidative phosphorylation in muscle cells after exercise in symptomatic, vitamin D–deficient subjects [208].

Another study revealed that vitamin D deficiency is linked with muscle atrophy, increased oxidative stress, and decreased mitochondrial functions in the multifidus muscle in patients [209]. Regarding bone health, hypovitaminosis D represents a risk factor for decreased bone strength in primary mitochondrial disease in human subjects [210].

Vitamin K2

There are two types of vitamin K: phylloquinone, or vitamin K1; and menaquinones, or vitamin K2. Vitamin K1 is derived from green, leafy vegetables such as spinach, kale, broccoli and cabbage, and is best known for the role it plays in blood clotting.

Vitamin K2 is better known for its role in bone and heart health, and is found in grass fed animal products such as meat, eggs, liver and dairy, as well as in fermented foods, including sauerkraut, certain cheeses and the fermented soy food natto.

Vitamin K2, a fat-soluble vitamin, also has antioxidant effects and is neuroprotective. In one study, researchers even revealed vitamin K2 modulates mitochondrial dysfunction caused by neurotoxins (2). They exposed SH-SY5Y cells, which serve as a model for neurodegenerative disorders, to 6-hydroxydopamine (6-OHDA), a neurotoxic compound used to destroy neurons in the brain.

They then treated the cells with vitamin K2, which led to multiple improvements. While 6-OHDA induced abnormal mitochondrial changes, vitamin K2 significantly suppressed the negative changes.

Vitamin K2 also inhibited the accumulation of reactive oxygen species (ROS) and promoted mitophagy, which is the removal of damaged mitochondria via autophagy — an essential function to maintain cellular health. Writing in the journal Nutrients, the scientists explained (3):

“… [V]itamin K2 can reduces mitochondrial damage, and … this effect is related to the participation of vitamin K2 in the regulation of the mitochondrial quality-control loop, through the maintenance of the mitochondrial quality-control system, and repair mitochondrial dysfunction, thereby alleviating neuronal cell death mediated by mitochondrial damage.”

6. Magnesium and Molecular Hydrogen

Magnesium

Magnesium can help increase oxidative capacity, the ability of your mitochondria to produce ATP from oxygen. Most people only tend to focus that oxidative capacity only depends on the availability of oxygen, however, the truth is this activity also critically relies on your mitochondria.

A study showed that at the cellular level, magnesium improved mitochondrial function with increased ATP, decreased mitochondrial ROS and Ca2+ overload, and repolarized mitochondrial membrane potential. In conclusion, Magnesium supplementation improved mitochondrial function, reduced oxidative stress, and prevented diastolic dysfunction in diabetes mellitus.

Our preference for magnesium supplementation is magnesium threonate as it appears to more efficiently penetrate cell membranes, including your mitochondria. It penetrates your blood-brain barrier and may help improve memory and it may be a good alternative to reduce migraine headaches.

Molecular Hydrogen

Molecular Hydrogen provides an extra layer of protection against sun damage and mitigates the effects of vegetable oils. It operates at the cellular level by neutralizing harmful free radicals, especially hydroxyl radicals. It can also penetrate cell membranes to target inflammation and oxidative damage directly at the source while preserving beneficial reactive oxygen species (ROS). Beyond its protective role, H2 boosts energy levels and enhances recovery, making it a valuable support for cellular health, particularly when dealing with sun exposure and dietary challenges from vegetable oils.

Note: Most Molecular Hydrogen tablets uses pure elemental magnesium as its carrier and provides you with approximately 80 mg of magnesium per tablet. So, you receive also highly bioavailable magnesium for a healthy brain, muscles, cells, kidneys, and heart.

Related: Best Molecular Hydrogen Tablets

7. Glycine and NAC

Glycine is a nonessential amino acid, as your body can manufacture some on its own. However, most of us do not make enough glycine to maximize its health benefits, which include increased longevity and protection against age-related disease.4

While it’s long been suggested that age-related mutations in mitochondrial DNA are responsible for making mitochondria less efficient as you get older, Japanese researchers suggested epigenetic changes may, instead, be the key players.

Further, they were able to restore gene regulation in aging mitochondria to a more youthful state using glycine.6 According to the study, “Treatment of elderly fibroblasts with glycine effectively prevented the expression of these aging phenotypes.” (7)

Collagen — the most abundant protein in your body (8) — is made mostly of glycine. It’s also a precursor to glutathione, a powerful antioxidant that declines with age. However, inducing autophagy and mimicking methionine restriction (9) may be behind glycine’s antiaging effects. Even intermittently restricting methionine leads to benefits like improved glucose homeostasis, reduced obesity and protection against fatty liver. (10)

Researchers at Baylor College of Medicine also looked into supplementation with a combination of glycine and N-acetylcysteine (NAC), two glutathione precursors known as GlyNAC when taken together.

They had previously shown that young mice deficient in glutathione had mitochondrial dysfunction, and supplementing with GlyNAC in older mice not only improved glutathione deficiency but also mitochondrial impairment, oxidative stress and insulin resistance. (11)

Additional research they conducted in HIV patients,12 and found GlyNAC supplementation improved “deficits associated with premature aging” in this population.13 This included improvements to oxidative stress, mitochondrial dysfunction, inflammation, endothelial dysfunction, insulin resistance, genotoxicity, strength and cognition.14

A subsequent pilot trial in older humans found similar results, with GlyNAC supplementation for 24 weeks correcting glutathione deficiency and improving multiple measures of health, including mitochondrial dysfunction, endothelial dysfunction, inflammation, cognition, strength and more.15

8. 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)

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. (source)

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].

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.

Read More: Melatonin 101: What You Need to Know

9. Creatine

Your body actually makes about 1 to 2 grams of creatine a day from amino acids — and this compound plays a central role in maintaining your cellular energy.

Creatine acts like a rechargeable battery for your cells, helping to rapidly regenerate adenosine triphosphate (ATP), your body’s energy currency, especially in high-demand areas like muscles, nerves and blood vessels. The real breakthrough? Research shows creatine isn’t just for muscles — it also helps your blood vessels work better, keeps them flexible and improves how well oxygen reaches your tissues.

This matters if you're over 50 or have blood sugar or weight issues, because stiff or weak blood vessels raise your risk for heart problems. Here's what the latest research found about how creatine improved artery health and metabolism in older adults.

A 2024 study in the journal Nutrients looked at how creatine affects the blood vessels of older adults who aren’t very active. For four weeks, participants took creatine every day. Then, after a short break, they switched to a placebo so researchers could compare the results.

Creatine Helped Older Adults Improve Blood Flow in Just Four Weeks - After four weeks of creatine use, their arteries worked better. Specifically, their endothelial function improved, meaning their blood vessels could relax and open more easily during blood flow. After taking creatine, flow-mediated dilation (FMD), which measures how much arteries expand when blood flow increases, improved from 7.68% to 8.9%. That sounds small, but even a 1% increase in FMD is linked to a 13% lower risk of heart problems.

Oxygen delivery through small blood vessels improved too — In smaller vessels, oxygen delivery to tissues also got a big boost. This matters because better oxygen flow helps your muscles, brain and organs recover, heal and perform more efficiently.

Creatine lowered fasting blood sugar and triglycerides — After 28 days, the participants’ blood sugar dropped from prediabetic levels to a healthier range. Their triglycerides, which are fats in the blood linked to heart disease, also went down significantly. These changes happened without any other lifestyle changes — just from adding creatine.

Your body uses the amino acid arginine to make creatine — but it also uses arginine to produce nitric oxide (NO), a gas that helps relax and open your blood vessels. When you get creatine from supplements, your body doesn’t need to use as much arginine to make it. That means more arginine is available to support healthy blood flow.

10. 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).

11. 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).

12. 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)

Other promising supplements

Studies are increasingly showing that mitochondrial illnesses are fueled by oxidative stress; implicating the use of antioxidants such as natural vitamin E and NAC (the precursor to glutathione) as well as glutathione as additional treatment considerations. We know that the sirtuin pathways are boosted by resveratrol and ECGC-green tea extract; implying mitochondrial benefit.

Branched-chain amino acids (BCAA) and creatine are all pro-mitochondrial health supplements, despite being poorly studied for this particular issue. Finally, there is emerging data for mitochondrial health with berberine, magnesium threonate and selenium. B vitamins are likely involved as well.

Mitochondrial Dysfunction and Disease

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.

How are mitochondrial health and metabolic syndrome related?

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 strong connection between mitochondrial health and diabetes has been known for some time. A review published in the Journal of Diabetes Investigation in 2010 examined the body of evidence pointing to mitochondrial dysfunction as a key player in diabetes development.

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.

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.

Mitochondria and Aging

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. Let’s say that this theory is true. What, then can we do to save our precious mitochondria and therefore slow the aging in our cells and help prevent diseases?

Mitochondrial Dysfunction Destroys Gut Health

Mitochondrial health and Gut Health

Restore gut health — Addressing gut microbiome imbalances is crucial for maintaining cellular energy. Focus on consuming beneficial bacteria and limiting fiber intake if pathogenic bacteria dominate your gut. Probiotic supplements and dietary adjustments help restore a healthy balance of gut flora, supporting mitochondrial function.

Related:

Diet and Mitochondrial Health

Anti-Inflammatory Diet

Eating an anti-inflammatory diet is one of the easiest ways to improve mitochondrial function. Polyphenol-rich foods such as blueberries, red and purple foods (e.g. raspberries and purple cabbage), and many fresh green foods are high in healthy mitochondrial-boosting polyphenols.

A foundational dietary strategy is to eat the right fuel, focusing on an ancestral diet and avoiding highly processed foods. Processed food diets prevent your body from efficiently burning fat as its primary fuel. Once you focus on whole foods and become an efficient fat burner, you automatically minimize the oxidative stress placed on your mitochondria.

Meal timing is another important factor. One of the worst things you can do to your mitochondria on a regular basis is eating shortly before going to bed. Ideally, eat your last meal of the day at least three hours before bedtime.

By supplying your body with food at a time when your body needs it the least (since you're sleeping), excessive amounts of free radicals end up being formed, which then spill out and damage mitochondrial DNA. Excess carbohydrates, in particular, result in a backup of electrons that causes the production of superoxide.

Optimize your carbohydrate intake for cellular fuel

Carbohydrates play a key role in supporting your mitochondrial function. Glucose, derived from carbohydrates, serves as your cells' preferred fuel source for energy production. The key is to choose the right types and amounts of carbohydrates.

Most adults need a daily intake of around 200 to 250 grams of targeted carbohydrates to support cellular energy. If you lead a more active lifestyle, you likely need even more. It's important to reintroduce carbohydrates into your diet gradually, however, giving your gut microbiome time to adapt.

Carbs Made Simple: A Color-Coded System to Guide Your Gut Health Journey

This approach recognizes that the traditional complex vs. simple carb dichotomy likely does not tell the whole story when it comes to individual health outcomes.

Instead, it suggests that the relationship between your gut health and carbohydrate metabolism could be key to unlocking improved overall wellness. It's not about following a one-size-fits-all diet, but rather about understanding how your unique gut biology interacts with different types of carbohydrates.

Surprisingly, for many people, this approach favors simple carbs over complex ones. This is because they usually have less-than-optimal gut health. If you have a compromised gut system and you consume complex carbs, the fiber and prebiotics in these carbs can feed oxygen-tolerant gut bacteria and worsen your symptoms. If you have dysbiosis, avoid fiber until your gut heals. In an unhealthy gut environment, complex carbohydrates like fiber feed harmful bacteria that multiply and eventually die off, releasing a highly virulent endotoxin called lipopolysaccharide (LPS). In addition to causing digestive issues, when LPS enters your bloodstream through a compromised gut barrier, it leads to a severe condition known as endotoxemia.

The following chart breaks down several types of carbohydrate sources and how they fit into this plan. We can categorize them into three groups: green, yellow and red.

In the green category are the most easily digestible simple carbs that provide quick energy without overtaxing your compromised digestive system. You will focus on these carbs initially, because simple carbs provide a quick energy boost for your cells and mitochondria. It's like giving your body's energy factories an immediate fuel injection, while allowing your gut to rest and heal at the same time.

Next is the yellow category, which includes carbs that offer more nutrients and fiber compared to the green category, yet are still relatively easy on the digestive system. Finally the red category, the most complex carbs, offers many health benefits but can be challenging for a compromised gut to handle.

So how can you begin implementing this approach? If you have severely compromised gut health, start with pure sugar water or dextrose water. This is a temporary measure to jumpstart the healing process. Mix one-half pound, up to a full pound, of pure dextrose (glucose) into a half gallon of water and sip it slowly all day. Don't drink more than an ounce at a time to avoid spiking your insulin. Unlike complex carbohydrates, dextrose is absorbed in your small intestine and doesn't feed bacteria in your colon, minimizing the production of harmful endotoxins. This strategy allows for gradual gut healing without worsening dysbiosis.

Once your gut health has improved, you can switch your primary carb source to whole foods. More than likely, you'll also need to eat more frequently than you're used to during this transition to avoid hypoglycemia. Eating every three to four hours, with snacks throughout the day, is crucial when relying on simple carbs for energy.

If your gut is generally healthy or you have only minor gut issues, start with easily digestible options like white rice, fruit juices with pulp, and whole fruits. As your gut adjusts, consider adding root vegetables, then non-starchy vegetables, starchy vegetables like sweet potatoes or squash, beans, legumes and, finally, minimally processed whole grains.

As your mitochondrial energy production continues to improve and your gut starts to heal, you will begin the transition back to complex carbs. This is a slow and steady process — don't rush it.

Once you're able to include more complex carbohydrates in your diet, you'll start to notice significant benefits. You'll be able to extend the time between meals to between four and six hours, and many people find they can comfortably switch to a three-meals-a-day approach. This is because complex carbs digest more slowly, providing a steady stream of energy.

Intermittent Fasting

Using intermittent fasting methods such as timed eating and intermittently “going keto” are also mitochondrial boosters.

Exercising For Mitochondrial Health

Many types of exercise are mitochondria-healthy. Walking is great. Running is great. Weight training is great. Yet, the very best type of exercise for your mitochondria is high-intensity interval training (HIIT). This doesn’t need to be complicated, but do get medical clearance if this is a new activity for you.

You can do HIIT outside, too of course. If you have access to a track, great! If not, use a treadmill if you’re inside or run in your neighborhood if you’re outside. Whatever gets you short of breath. Then, walk until you catch your breath and you can even lie down on your back for faster autonomic neurological adaptation for up to 90 seconds if you need that long to catch your breath.

Exercise also upregulates genes like PGC-1 alpha and nuclear gene factors like Nrf2. These genes help your mitochondria become more efficient. Mitochondria are also vulnerable to emotional stress and environmental toxins, like heavy metals.

Heat Shock Proteins

Heat shock proteins produced by extreme cold or extreme heat are great for your mitochondria. Cold exposure is an easy way to give your mitochondria a boost. Studies have demonstrated benefits with “ice jackets”, facial submersion, and ice baths. Even cryotherapy tanks! And “ice swimming.” Based on what I personally find tolerable and affordable, you can get enough of a boost by doing the following. At the end of your daily hot shower, just turn the temperature to cold for 30 seconds. It is mostly quite invigorating!

Infrared Saunas

Far-infrared (FIR) and near-infrared saunas are another way to generate heat shock proteins. An FIR is a great investment in your health, as it is also a great way to do a bit of a detox.

Regular use of a near-infrared sauna may offer help for both detoxification and stress relief.

As an added benefit, 95% of melatonin is produced in your mitochondria in response to near-infrared light. Melatonin is an antioxidant that helps mop up ROS that damage your mitochondria. So, by getting plenty of near-infrared exposure, either from a near-infrared sauna or sun exposure during the day, your mitochondria will be bathed in melatonin, thereby reducing oxidative stress. (source)

Meditation and Yoga

Meditation and yoga also boost your mitochondrial output.

Other Lifestyle Strategies

Ten minutes of direct sunlight is great for a burst of mitochondrial activity. Conversely, most data suggest that fluorescent lighting puts a damper on ATP production and mitochondrial biogenesis. The data is rather murky when it comes to EMFs, blue-blocking glasses, and so on, but it’s something to watch, as there seems to be some correlation between better health and less high-level EMF exposure, as well as less blue light exposure.

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-l-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.

Read more: This article is part of the mitochondrial and cellular health series.

Sources and References:

https://www.onedaymd.com/2024/11/how-to-optimize-mitochondrial-health.html

https://kimcrawfordmd.com/2021/03/6-habits-and-the-7-best-supplements-to-improve-mitochondrial-function/

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