In our first 4 blogs on the mitochondria, we looked at what they do, as well as various aspects that created MD. Here we are going to take a deeper dive into what supplements and lifestyle issues that can be done to improve mitochondrial health.

To rejuvenate the mitochondria, we need to:

• Prevent mitochondrial impairment
• Purge damaged mitochondria
• Protect and produce healthy, new mitochondria

The key to these steps is making certain lifestyle changes that go deep down to the biological level to improve your mitochondria’s ability to process food and oxygen and convert them to energy. 

These include: 

• Minimizing exposure to mitochondria-damaging molecules (free radicals) 
• Eating healthful foods rich in antioxidants (to fight free radicals) 
• Eating a protein- and fat-rich oxygenating foods to supercharge the mitochondria 
• Avoiding foods that harm mitochondrial functioning 
• Taking the ideal supplements for mitochondrial health 
• Using exercise to eliminate damaged mitochondria 
• Building muscle for higher concentrations of mitochondria 
• Improving your breathing hygiene and oxygenation 
• Practicing stress reduction techniques
• Getting adequate sleep for mitochondrial regeneration

This simple and proven program not only helps short-term issues like inflammation, fatigue, and insomnia, but can prevent premature aging, Alzheimer’s, cancer, cardiovascular disease, and many other chronic health issues.

Important Nutrient Supplements

Top of the list of supplements needed to repair mitochondria health are antioxidants. We will be reviewing several in the following section. We will also need a high-quality multivitamin/mineral full of essential or orthomolecular nutrients including vitamins A, B complex, C, D, E and K, and essential minerals such as magnesium, calcium, zinc, selenium, chromium, potassium and more. When buying a multi, it is best if it is one that has natural folates instead of “folic acid” which is synthetic. Synthetic “folic acid” is not the same as “folates.” Studies are now showing that folic acid that’s been added for good reason (to processed foods such as bread and pasta to fortify the B vitamins stripped by the manufacturing process), can be harmful to your body, mitochondria, and methylation pathways. It’s particularly important for pregnant mothers, so make sure your prenatal vitamins have natural folates, rather than folic acid.

D-Ribose: Any amount of D – ribose given to energy – depleted cells will help. Even doses as low as 500 milligrams could be beneficial, although likely are not nearly enough to make a real improvement in health. Standard dosages range from 3 to 5 grams per day.

Glutathione (GSH): Glutathione (GSH) is one of the masters of all antioxidants and production of it depends on the availability of three amino acids—glutamate, glycine, and cysteine. It will help neutralize free radicals, viruses, and all types of toxins, and will also facilitate DNA synthesis and repair.

I do suggest you try to eat food high in GSH as that is both the best and the most economical form of it. We often do have to supplement this also. Folates (vitamin B₉) will boost glutathione production. 

Dosage: 200 – 1000 mg, but often using foods or NAC and folates is better.

CoQ₁₀: CoQ₁₀ Enzyme or Coenzyme Q-10 (CoQ₁₀) is a rate limiting nutrient factor in the electron transport chain and has a key role in producing ATP in the Krebs Cycle and improving energy levels in all tissues. It is at its peak levels at 20 years old, slowly reducing as we age. CoQ₁₀ helps to regulate insulin levels for diabetes while lowering high blood pressure. 

Not only is CoQ₁₀ a great antioxidant, but it is also vital for mitochondria stability and ETC function. It also regulates gene expression and apoptosis. It has been shown to have anti-inflammatory, redox modulation and neuroprotective effects. It should almost be classified as a vitamin, truly becoming so for most people over 55 years of age, starting to be reduce by early 30’s but barely created in people over 50 years of age.

Even though we obtain some from our food, it is usually way below therapeutic levels. The other problem is being fat soluble, it has a low absorption rate, which is a main factor limiting its therapeutic use. Research has shown that oil – based formulations (typically soft gels) are much better absorbed, and water – dispersible liposomal or pre – emulsified formulations are even better. Ubiquinol (reduced CoQ₁₀) seems to offer much better absorption than ubiquinone (oxidized CoQ₁₀), and water – soluble (solubilized) ubiquinol is even better absorbed.

I personally feel if a person can only afford one supplement for treating mitochondria dysfunction, this is the one. We usually suggest the ubiquinol form as it is substantially better. Even though 80% of CoQ₁₀ is found in the mitochondria, it is also used in microsomes, Golgi apparatus and plasma membrane, showing that it has other functions. Many long-lived mammalian species have much higher levels of CoQ₁₀ than short-lived species.

Dosage: 100–300 mg of regular CoQ₁₀, less of ubiquinol.

L-Carnitine: L-carnitine’s importance is like CoQ₁₀ and is a key ingredient to help shuttle lipids (fat) through the mitochondrial membrane and into the mitochondria, where it can be burned as fuel to produce energy, ATP. The rub here is even though it can be produced by our body, like CoQ₁₀ is reduced with aging. It is considered a nonessential amino acid since our body can make it in the liver and kidneys. It is readily stored in the skeletal muscles, heart, brain, and sperm. However, genetic variants may reduce the production of this essential nutrient.

The most important thing here is that L-carnitine is important for transport of long fatty acids into the mitochondria so can subsequent beta-oxidation to produce ATP. The take-home is that most of the dietary fatty acid we consume are long chained and L-carnitine is the ‘tugboat’ that help achieve this. This process is called acylcarnitine (‘acyl’ meaning attached to L-carnitine). 

Mitochondrial Membrane Lipids: Phosphatidylcholine and Omega 3 fatty acid (especially docosahexaenoic acid, DHA): Omega 3 fatty acid are key to restoring mitochondrial and other cellular membrane. I typical suggest Krill as the best source as it is mostly in a phosphatidylcholine form. These lipids are essential for protection of both inner and outer membranes for the mitochondria. Krill also contains astaxanthin a high-quality antioxidant that we will mention later.

Dosage 1000 mg twice daily. 

Magnesium: Magnesium has been linked to the reduction of mitochondrial DNA mutation. About 50 percent of us are magnesium deficient! Additionally, magnesium supports other health benefits such as helping maintain a healthy heart and muscles and a powerful immune system. Magnesium is also a key cofactor for energy production via the methylation pathway, particularly the methionine pathway. 

Dosage: 300 mg twice a day, with or without meals (reduce levels if you experience diarrhea).

Pyrroloquinoline Quinone (PQQ): Traditionally, it was believed that generating new mitochondria (mitochondrial biogenesis) could only occur because of strenuous exercise or extreme calorie restriction, which is why research on PQQ (pyrroloquinoline quinone) is so exciting. Early in 2010, researchers found PQQ not only protected mitochondria from oxidative damage, but it also stimulated the growth of new mitochondria! Pyrroloquinoline quinone is a coenzyme’s presence in interstellar stardust has led some experts to believe it played a pivotal role in the evolution of life on Earth.  PQQ is found in every plant species tested to date, but neither humans nor the bacteria that colonize the human digestive tract have shown the ability to naturally produce it. This has led researchers to classify PQQ as an essential micronutrient. Recently, PQQ was even chosen as one of the ten most important compounds for longevity by the Children’s Hospital Oakland Research Institute.

Dosage: 10 – 20 mg daily

Creatine: Buffered creatine monohydrate is a stable bioavailable form of creatine. It provides extra support for energy production, muscle enhancement and athletic performance. One of the issues of using it is the unpleasant side effect of nausea, diarrhea, cramps and bloating due to the conversion into the metabolite creatinine. To prevent this, use the buffered creatine monohydrate. 

Dosage 1000 – 2000 mg daily

Rhodiola rosea: also known as “golden root,” is a popular adaptogenic herb, which means it works in the cells to normalize their function and stimulate healing. Rhodiola support the adrenal glands, helping the body with stress, anxiety, and fatigue. It will enhance mitochondrial energy production by activating the synthesis of ATP as well as working as an antioxidant.  

Dosage: 200–400 mg per day, in the morning

Alpha-Lipoic Acid (ALA): helps restore other antioxidants if they’ve been used up in the body. ALA is a bit unique in that it can act as both water soluble and fat soluble. It is specific for its ability to target the mitochondria. Further, ALA has an important role in the production of glutathione, which it can shuttle into your brain easily. It can be especially helpful for people suffering from Alzheimer’s for this reason. 

When combined with L-carnitine – it has a profound antiaging benefit by restoring youthful activity levels, cognitive performance, and heart function. R (+) Alpha – Lipoic Acid and Its Stability I’ll add just a couple of quick notes on the types of nutritional supplements you will find on the market. As this is the only form the body can use. 

Dosage: 100–300 mg, divided twice a day, with a meal.

NADH: Reduced Nicotinamide Adenine Dinucleotide: is a nutrient essential to human health, and without it the person will display symptoms such as dermatitis, diarrhea, dementia and eventually death, called pellagra. Studies show that stabilized oral NADH can reduce symptoms of fatigue, cognitive dysfunction and dementia, and other neurological disorders such as Parkinson’s disease. Niacin, (B₃), nicotinamide or nicotinic acid can be ingested as precursor supplements to NADH and are also found in seafood and animal protein, avocado, nuts, green peas, sunflower seeds, and chia seeds. 

Dosage: 10–20 mg per day, in the morning

Astaxanthin: is one promising nutrient that may improve your endurance by boosting mitochondrial antioxidant defenses. It is a pinkish orange carotenoid found only in two ocean sources: a micro-algae rich in reddish pigment and seafood such as tiny crustaceans called krill and wild salmon.

Dosage 5-10 mg daily

Vitamin D₃: is an orthomolecular prohormone, and if deficient can challenge energy storage and energy production during recover phase from moderate exercise. The results of studies in mice suggest that vitamin D deficiency may impair muscle mitochondrial function, impacting on energy production in muscle cells and so potentially affecting muscle performance and recovery. While further research will be required, preventing vitamin D deficiency in older adults could feasibly help to maintain better muscle strength and function andreduce age related muscle deterioration.

Dosage: 1-3000 mg per day (get a vitamin D 25-10 blood test for best dosage levels)

Vitamin C: is a well-known antioxidant and required to synthesize l-carnitine. It takes 11 cups of fruits and vegetables to get at approximately 1000 mg of Vitamin C.

Dosage 500 mg three time daily

Vitamin E: is an antioxidant useful for lipid-based function. It is high in coconut, red bell pepper, walnuts cranberry rice bran, ground cinnamon, flax seeds, palm oil, cocoa butter, and oats.

Dosage 400 – 800 IU daily 

NAC (N-Acetyl Cysteine): is a precursor nutrient for the synthesis of glutathione. It’s also known for its potent antioxidant properties. It’s great to use during allergy season and respiratory infections to break up the congestion and clean up the lungs as a mucolytic. I call it the all-natural decongestant. 

Magnesium: Most practitioners highly under rate the need for magnesium. This of course has significance throughout the body. The mitochondria are stored in the body mostly in our intracellular, often bound to ATP. In fact, ATP production is really a Mg-ATP process. 

Cardiovascular health is quite dependent on magnesium as it plays a major role in heart muscle relaxation. Magnesium deficiency, hypertension, ischemic heart disease, CHT, mitral value prolapses. It’s also been linked to preeclampsia and eclampsia, asthma, insulin resistance and diabetes, metabolic syndrome, osteoporosis, and even colon cancer.

Shilajit: is a resin exudate that oozes from the rocks of the Himalayas during the summer months with anti-aging and life enhancement properties. It contains a substance called fulvic acid that provides potent antioxidant properties and magnifies the delivery of nutrients inside the cells to recharge the mitochondria. Shilajit also enhances the oxygen carrying capacity, improving blood circulation and combat high altitude sickness. I personally use a powdered form of nutritious superfoods and herbs—that includes both shilajit and ho shou wu—as part of my tonic called Jing Jing.

Dosage ½ teaspoon daily, usually in the morning

Ginseng: Panax ginseng has been known to regulated energy (Qi, Chi) in the body along with an extensive list of other functions from metabolic syndrome, cardiovascular, immunity, longivity and cognitive health. Ginseng has been shown to help regulate and protect mitochondrial function in the body. It can also modulate mitochondrial bioenergetic, significant improvement mitochondrial function. Ginsenosides have been shown to reduce harm done to mitochondrial from polluted environments by reduce oxidative stress. 

Dosage 1-3 gram of extract daily

Solar Flares: radiation from solar flares has shown to have a strong negative effect on mitochondria function responsible for a large range of health issues for astronauts. This has even started a strong debate if humans can travel, or spend long time in space, like a journey to mar. This ‘space weather’ does not affect most human on earth due to the ionosphere but has been shown to effect mitochondrial health of some sensitive people on earth. 

Cannabis: in 2012, French scientists discovered that mitochondria contained cannabinoid receptors on their membranes leading to research that the mitochondria have strong links to the endocannabinoid system (ECS). This research confirmed that cannabidiol (CBD) and tetrahydrocannabinol (THC) — the two main phytocannabinoids from the cannabis plant — can directly and indirectly impact the mitochondria. 

There are three major ways that plant and endogenous cannabinoids can directly modulate mitochondrial function – by 1) activating CB1 receptors on the mitochondria; 2) perturbing the mitochondrial membrane; and 3) binding to other (non-cannabinoid) receptors on the mitochondria’s surface.

The ECS regulates numerous cellular and physiological processes through the activation of receptors targeted by endogenously produced ligands called endocannabinoids. Importantly, this signaling system is known to play an important role in modulating energy balance and glucose homeostasis. The ECS modulates the function of mitochondria, which plays a pivotal role in maintaining cellular and systemic energy homeostasis, in large part due to their ability to tightly coordinate glucose and lipid utilization. Because of this, mitochondrial dysfunction is often associated with peripheral insulin resistance and glucose intolerance as well as the manifestation of excess lipid accumulation in the obese state. Many of the disease problems related to MD are directly correlated to either glucose and or lipid issues. A growing body of scientific data indicates that cannabidiol (CBD) and tetrahydrocannabinol (THC), Can affect mitochondria, both directly and indirectly. It turns out that many of the biological pathways that involve mitochondria—including energy homeostasis, neurotransmitter release, and oxidative stress—are modulated by endogenous and exogenous cannabinoids.

Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system. But research on cannabinoids often seems to be riddled with contradictions. Cannabinoids are notorious (in science and lived experience) for exerting opposite effects in different situations.  This is due to it biphasic function both to dosage and length of consumption without a break. 

According to a 2016 report in Philosophical Transactions of the Royal Society (London): “Cannabinoids as regulators of mitochondrial activity, as antioxidants and as modulators of clearance processes protect neurons on the molecular level… Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the aging process on the system level.” Ageing, neurodegeneration, metabolic disorders, and cancers are all linked to mitochondrial activity—or lack thereof.

In fact, growing evidence suggests that cross – talk between the ECS and the free – radical signaling systems acts to modulate functionality of both the ECS and redox homeostasis. Further, as just discussed, studies reveal that interactions between the ECS and free – radical signaling systems can be both stimulatory and inhibitory, depending on cell stimulus, the source of free radicals, and cell context. While such cross – talk might act to maintain cell function, abnormalities in either system could propagate and undermine the stability of both systems, thereby contributing to various pathologies associated with their dysregulation.

As mentioned above, by regulating innumerous cellular processes beyond energy production, mitochondria exert a plethora of functions that are particularly crucial for one of the most energy-demanding organs of the body, such as the brain. Thus, the elucidation of novel mitochondrial CB1-dependent functions can open great opportunities in the potential therapeutic aspect of cannabinoid drugs. Moreover, it will be very important to dissect the possible involvement of mitochondrial CB1 receptors in pathologic conditions were CB1 receptors exert a specific role. Overall, thanks to the use of new tools such as advanced imaging, genetic, viral, and behavioral techniques, researchers in the cannabinoid field must fully understand how CB1 receptors, with or without the involvement of the mitochondria, are specifically exerting their physiological or pathological functions.

Medicinal Mushrooms

Mitochondria play a central role in non-alcoholic fatty liver disease (NAFLD) progression and in the control of cell death signaling during the progression to hepatocellular carcinoma (HCC). Associated with the metabolic syndrome, NAFLD is mostly driven by insulin-resistant white adipose tissue lipolysis that results in an increased hepatic fatty acid influx and the ectopic accumulation of fat in the liver. Upregulation of beta-oxidation as one compensatory mechanism leads to an increase in mitochondrial tricarboxylic acid cycle flux and ATP generation. The progression of NAFLD is associated with alterations in the mitochondrial molecular composition and respiratory capacity, which increases their vulnerability to different stressors, including calcium and pro-inflammatory molecules, which result in an increased generation of reactive oxygen species (ROS) that, altogether, may ultimately lead to mitochondrial dysfunction. 

Mushroom-enriched diets, or the administration of their isolated bioactive compounds, have been shown to display beneficial effects on insulin resistance, hepatic steatosis, oxidative stress, and inflammation by regulating nutrient uptake and lipid metabolism as well as modulating the antioxidant activity of the cell. In addition, the gut microbiota has also been described to be modulated by mushroom bioactive molecules, with implications in reducing liver inflammation during NAFLD progression. Dietary mushroom extracts have been reported to have anti-tumorigenic properties and to induce cell-death via the mitochondrial apoptosis pathway. 

Polysaccharides found in several medicinal mushroom, especially Ganoderma species, can induce apoptosis by the elevation of p53 and Bax expression, downregulation of Bcl-2, activation of caspases 3 and 9, mitochondrial membrane potential loss, mitochondrial cytochrome c release, and intracellular ROS production. In addition, the polysaccharides increased immune organ index, induced lymphocyte proliferation, and enhanced cytokine levels in serum. This data suggests that these polysaccharides exert an antitumor activity by inducing mitochondria-mediated apoptosis and enhancing systematic immune functions. Similar results were also observed in sarcoma 180-bearing mice.

The polysaccharides activated the mitochondria-mediated apoptosis pathway by stimulating the activation of a family proteins to release cytochrome c and Smac having a potent effect on cell cycle arrest in G(1) and/or S phase and induce apoptosis in HepG2 and Bel-7404 cells.

ROS-Dependent mitochondria molecular mechanisms are underlying antitumor activity of polysaccharides in human breast cancer.

Turkey tail mushroom has shown to dramatically reduce oxidative stress and neuroinflammation in neurodegenerative disorders. By reducing Reactive Oxygen species (ROS,) Coriolus versicolor, has been shown to down grade cancer and Alzheimer’s via mitochondria function.

Other botanicals that show some promise in the area:

• Gotu Kola (Centella Asiatica)
• Gynostemma
• Ginseng
• Chinese skullcap 
• Danshen (Salvianolic acid A)
• Caffeic acid
• EGCG (Green tea)
• Curcumin 
• Bitter melon
• Resveratrol 
• Leucine

Exercise and Physical Activity 

The beneficial effects of regular, nonexhaustive physical activity have been known for a long time. Regular exercise is associated with diverse health benefits, such as reduced threat of cardiovascular diseases, cancers, diabetes, and, in general, a lower risk of all-cause mortality. 

The resulting mitochondrial biogenesis is the reason exercise has been linked to improvements in cardiovascular health, cognitive health, psychological well-being, lower diabetes risk, healthy muscles and bones, cancer prevention, reduced risk of premature death from all-cause mortality, and longevity. “Movement is medicine” is a catchphrase we should all live by. 

Cognitive Health and the New Frontier for Physical Activity

While much research has been conducted over the years on the cardiovascular benefits of exercise (so much in fact that I’ve decided against discussing it here), recent years have seen a focus on brain and cognitive function take center stage with an aging population. Both resistance and aerobic training have been shown to improve different types of memory, executive functioning, and functional plasticity. It’s been known for decades that aerobic exercise can increase the number of mitochondria in your muscle cells by up to 50 percent in as little as six weeks. To get the benefit, however, you need to do aerobic exercises (such as running, cycling, swimming, or walking) at an intensity that’s at least half of your maximum capacity. This intensity needs to be sustained for at least fifteen to twenty minutes per session, three to four times a week. 

Cold Exposure

Cold temperatures have a profound effect on the mitochondrial number in animals. Exposing rats to swimming in cold temperatures (23⁰C) increased mitochondrial generation by increasing the protein responsible for initiating mitochondrial synthesis. Similar results were seen in rats’ liver and skeletal muscle cells after cold exposure for 15 days. These findings have not been confirmed in humans.

Ketogenic diet

The ketogenic diet is a high-fat, low-carb diet that is claimed to switch your body from

running on carbs to running on fats. When fats are broken down for energy, small molecules called ketone bodies are produced. These molecules are used to produce ATP instead of glucose. Remember, as seen above the use of carnitine is important for this mechanism to work well. 

Some researchers believe that this results in improved mitochondrial function (PGC-

1alpha, SIRT1/3, AMPK activation), higher levels of ATP from the electron transport chain,

and overall cellular health. One study found that a ketogenic diet slowed down mitochondrial myopathy (a muscle disease) in mice in part by increasing the number of new mitochondria (mitochondrial biogenesis). Human studies are lacking.

Pulling It All Together

So, you can see there are many options readily available to most individuals who want to improve the health of their mitochondria. Not any one therapy is ideal, however, and it seems that the best outcomes are from a combination of numerous therapeutic agents and exercise (exercise must always be included in any program targeting mitochondria), especially high-intensity interval training. Other areas getting some current research attention include intermittent hypoxia and intermittent fasting—we can expect some eye-opening results to come from these studies (and their recommendations are sure to make their way into my personal mitochondrial regimen). There are many ways to approach developing a mitochondrial regimen, depending on what health objectives you’re trying to achieve and what medical history or pre-existing conditions are factors. Even then, as research shapes my approach, my recommendations and personal mitochondrial regimen could change, and likely will have changed by the time you read this. 

Mitochondrial medicine is a constantly evolving body of knowledge, and we’re learning more about the mitochondrial benefits of different nutrients and botanicals every day. 

We are still in the early days of understanding how mitochondria health has such a global effect on the health of a person. We hope that this introduction will give you answers to a few questions on MD and at least give you a starting point for being able to do more research on this area. 

We are also going to follow this series with a set of blogs looking deeper into the biochemistry and biomechanics of how the mitochondria produces most of the energy for our body.