For Canadian Herb Conference: Nov. 23 @ 2:15 PST – https://herbconference.com

By Terry Willard ClH, PhD

In our first blog in this series, (https://www.drterrywillard.com/__trashed/ ) we saw that the mitochondria, the Hearth of our cells, where mitochondria Qi Translator from the Quantum realm. In the Second blog the Mitochondria and aging( https://www.drterrywillard.com/back-to-the-winter-hearth-mitochondria-and-aging-2-4/). I the third blog (https://www.drterrywillard.com/back-to-the-winter-hearth-treatment-for-mitochondria-dysfunction-md-3-4/) we looked at exercise and lifestyle issue that influence MD. In this blog we are going to finish out our Winter Hearth series with various supplement and botanicals that can improve mitochondria function.

Mitochondria Supplements of Interest

To rejuvenate the mitochondria, we need to:

• Prevent mitochondrial impairment.
• Purge damaged mitochondria.
• Produce and protect healthy, new mitochondria.

The key to these steps is making particular 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 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-vitamin, 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 seemingly good reason (e.g. 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.

More detail found in:

Mitochondria Supplements of Interest — Part 5

CoQ₁₀

Coenzyme Q₁₀ (CoQ₁₀) is a rate-limiting nutrient factor in the electron transport chain (ETC) 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-modulating, 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.

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.

CoQ₁₀ is very important for working on congestive heart failure (CHF) and dilated cardiomyopathy. Many studies from both sides of the aisle of pharmaceutical and natural medicine have shown it to be completely essential. Formulation here can really separate the results with the ubiquinol outshining the simple CoQ₁₀ products. It has also shown to be a great benefit to aiding in lowering high blood pressure. CoQ₁₀ reduces damage done by statin medications, one of the most over-prescribed pharmaceuticals. Often being able to replace the use of statins, it should certainly be consumed by anyone taking them. 

CoQ₁₀ is one of the safest nutrients taken with pharmaceutical cocktails, helping reduce damage created by them. It should certainly be taken when prescribed beta-blockers, a group of drugs typically prescribed for hypertension and arrhythmias, as they have been shown to deplete CoQ₁₀ levels—meaning for those who take beta-blockers, CoQ₁₀supplementation is recommended (as it is in statin therapy). In fact, CoQ₁₀, when given concomitantly with beta-blockers, was shown to reduce the fatigue that is usually induced by these drugs. However, people taking beta-blockers should be aware that there could be possible additive effects as there sometimes are when CoQ₁₀ is taken with blood pressure medications. The main drug that is of concern when supplementing with CoQ₁₀ is warfarin, a blood thinner. Many practitioners warn against taking the two together. Until recently, warfarin was considered first-line therapy for atrial fibrillation (fluttering of the heart—when the heart flutters and creates turbulence in blood flow, there is a greater risk of clots forming). Accompanied with suitable blood testing often starting off with low levels of CoQ₁₀ while slowly lowering warfarin can either reduce or eliminate warfarin use.

Research into neurodegenerative diseases has shown the CoQ₁₀ can help reduce issues like Huntington’s disease, amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and reduce ataxia (reduced control over voluntary movement). Parkinson’s disease has also been shown to be reduced by CoQ₁₀. 

As a person ages, they often have reduced recovery from stress responses. CoQ₁₀ has been shown to reduce and often abolish the recovery time.   

Dosage: 100–300 mg per day of regular CoQ₁₀, can cut in half if ubiquinol, but I still maintain that amount anyway.

CoQ₁₀ can be found in:

• Organ meats — heart, liver, and kidney.
• Some muscle meats — pork, beef, and chicken.
• Fatty fish — trout, herring, mackerel, and sardine.
• Vegetables — spinach, cauliflower, and broccoli.
• Fruit — oranges and strawberries.
• Legumes — soybeans, lentils, and peanuts.
• Nuts and seeds — sesame seeds and pistachios

CoQ₁₀ lives in cells throughout the body mostly concentrated in vital organs, which means animal organ meats have the highest amounts of CoQ₁₀ per 100 grams. For instance, a beef heart has 11.3 milligrams, and a beef liver has 3.9 milligrams. A chicken heart has 9.2 milligrams and chicken liver has 11.6 milligrams.

Fatty Fish: Fatty fish like trout, mackerel, and sardines contain CoQ₁₀. Mackerel provides about 6.75 milligrams per 100 grams and trout provides 0.85 milligrams per 100 grams. 

Meat: It’s not just animal organs that provide CoQ₁₀. Since it lives throughout the body, it is present in all meat forms. Beef muscle meat offers about 3.1 milligrams per 100 grams, chicken has 1.4 milligrams, and pork has 2.4 milligrams, while reindeer meat provides about 15.8 milligrams per 100 grams.

Soybeans: Products such as tofu, soy milk, and soy yogurt are a valuable protein source for people who don’t eat meat. Soybeans also have many other vitamins and minerals, as well as CoQ₁₀. Boiled soybeans have 1.2 milligrams per 100 grams. Other soy products contain less CoQ₁₀, with tofu at 0.3 milligrams and soy milk at 0.25 milligrams. 

Vegetables: Along with many vitamins and minerals, a lot of vegetables contain CoQ₁₀. Among them, broccoli has high CoQ₁₀ content, weighing in at 0.6 to 0.86 milligrams per 100 grams. 

Nuts and Seeds: Along with protein, heart-healthy fats, and other important nutrients, nuts and seeds provide CoQ₁₀ as well. Pistachios have 2 milligrams of CoQ₁₀ per 100-gram serving, peanuts have 2.6 milligrams, and sesame seeds have 1.7 milligrams.

L-Carnitine

L-carnitine’s importance is like CoQ₁₀ and is a key ingredient to help shuttle lipids (fats) 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 it 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.

Dosage: 400–500 mg per day

Food high in L-carnitine are:

• Red meat has the highest levels. A 4-ounce beef steak has an estimated 56 mg to 162 mg of carnitine. 
• Chicken, milk and dairy products, fish, beans, and avocado in smaller amounts. 

Vegans tend to get less carnitine from foods, but their bodies usually produce enough anyway.

Mitochondrial Membrane Lipids: Phosphatidylcholine and Omega-3 Fatty Acid (especially Docosahexaenoic Acid, DHA) 

Omega-3 fatty acids are key to restoring mitochondrial and other cellular membranes. I typically 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. 

Foods that are very high in omega-3:

• Mackerel (4,107 mg per serving)
• Salmon (4,123 mg per serving) 
• Cod liver oil (2,682 mg per serving) 
• Herring (946 mg per serving)
• Oysters (370 mg per serving) 
• Sardines (2,205 mg per serving) 
• Anchovies (951 mg per serving) 
• Caviar (1,086 mg per serving)
• Chia seeds (5,060 mg per serving)

Chia seeds are incredibly nutritious—they’re rich in manganese, selenium, magnesium, and a few other nutrients. A standard 1-ounce (28-gram) serving of chia seeds contains 5 grams of protein, including all eight essential amino acids, as well as 5,060 mg of omega-3 oil per ounce.

Walnuts are also very nutritious and loaded with fiber. They contain high amounts of copper, manganese, vitamin E, as well as important plant compounds. Make sure not to remove the skin, as it packs most of walnuts’ phenol antioxidants, which offer important health benefits. Omega-3 content: 2,570 mg per ounce (28 grams), or about 14 walnut halves.

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 presence in interstellar stardust and 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 effective compounds for longevity by the Children’s Hospital Oakland Research Institute. The science on PQQ is still young; most of the research has only been done in animal studies. 

In mice supplemented with PQQ for 8 weeks, mitochondrial function and number were increased significantly. This was seen as an increase in the amount of mitochondrial DNA found in the cells of these mice. Multiple cell tests investigated the effects of PQQ on mitochondrial number and function. PQQ seems to alter a number of proteins (increasing SIRT1, promoting PGC-1alpha production and CREB-phosphorylation) while reducing oxidative stress. 

While there are some human studies, it isn’t clear exactly how it can help your body. However, research shows that there may be some health benefits. PQQ is an antioxidant and based on research, it is shown to be more powerful at fighting free radicals than vitamin C. Antioxidants work better together, so it’s unclear if taking PQQ alone as a supplement can help stop any diseases.

PQQ might lower inflammation by lowering the C-reactive protein, interleukin-6, and other markers in your blood.‌ Substances that help memory, attention, and learning are sometimes called nootropics. Studies show that PQQ raises blood flow to the cerebral cortex. This is the part of your brain that helps with attention, thinking, and memory. This supplement also seems to prevent memory problems in older people.

PQQ is a potent antioxidant that promotes the production of mitochondria, increasing size and density in the cell. There is strong evidence that PQQ might play an important role in pathways important to cell signalling. PQQ also is a defense against mitochondrial impairment, mostly due to its antioxidant properties. If mammals are stopped from consuming PQQ, there is a wide range of systemic responses, including growth impairment, compromised immune responses, and abnormal reproductive performance. 

The stability of PQQ helps it be capable of carrying out thousands of redox catalytic cycles, whereas other bioactive quinones capable of redox cycles (e.g., epicatechin in green tea) tend to self-oxidize or form polymers (e.g., tannins), rendering then useless in further redox reactions. PQQ and its derivatives, IPQ, are widely distributed in animal and plant tissue ranging from pico- to nanomolar concentration.

Our bodies cannot make it, but PQQ can be found in a variety of foods including chocolate, parsley, green tea, peppers, kiwi fruit, celery, and papaya. From an evolutionary perspective, current evidence suggests PQQ is a component of interstellar dust, and since it’s been postulated that strong redox catalysts were required to trigger the earliest chemical evolutionary steps, the extraterrestrial origin of PQQ raises the question of its evolutionary importance to simpler life forms. This theory is especially interesting when you consider PQQ’s wide range of chemical properties, such as a redox catalyst and the ability to modify amino acids (e.g. oxidative deamination reactions). Could PQQ be our common point of origin with life in other areas of the galaxy?

Dosage: 10 – 20 mg daily

PQQ-rich foods include:

• cocoa
• parsley
• green peppers
• celery
• kiwi fruit
• papaya
• tofu
    These foods contain about 2-3 mcg per 100 grams. Green tea provides about the same amount per 120 mL serving.

• Fermented soybean products (e.g. Nattō)
• Green soybeans
• Spinach
• Field mustard (5.54 +/-1.50ng /g fresh weight)
• The PQQ content of even the most PQQ-rich foods is much lower than the amount you can get from a supplement (5 to 20 mg).

PQQ is also often found in breast milk. This is probably because it is absorbed from the fruits and vegetables consumed and passed into milk. Some people say that PQQ is an essential vitamin because at least one animal enzyme needs PQQ to make other compounds. Animals seem to need it for normal growth and development, but while you often have PQQ in your body, it’s unclear whether it’s vital for people.

NADH: Reduced Nicotinamide Adenine Dinucleotide 

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.

Food sources include:

• Seafood and animal protein
• Avocados
• Nuts
• Green peas
• Sunflower seeds
• Chia seeds. 

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

Vitamin D₃

Vitamin D₃ is an orthomolecular prohormone, and if the body is deficient there can be challenges in energy storage and energy production during recover phase from moderate exercise. Some individuals have genetic variants such as VDR Taq or VDR Bsm that block the metabolism and utilization of vitamin D₃.

The results of studies in mice suggest that vitamin D deficiency may impair muscle mitochondrial function, impacting on energy production in muscle cells and thus 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 and reduce age related muscle deterioration.

Dosage: 1000-3000 IU per day (get a vitamin D 25-10 blood test for best dosage levels)

Vitamin C 

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

Dosage: 500 mg three times daily.

Ginseng (Panax ginseng) 

Ginseng and their ginsenosides have been shown to be a powerhouse that can remedy many health issues. One of the reasons the ginsenosides play beneficial roles in the molecular pathophysiology of these diseases is by targeting mitochondrial dysfunction. Recent findings have shown that the ginsenosides target mitochondria regeneration and thus are useful for the treatment of multiple diseases including neurological disorders, cancer, heart disease, hyperglycemia, congestive heart failures, and inflammation.

Due to the extreme level of research done in China on ginseng and their ginsenosides, this following section is quite geeky. If you enjoy that kind of stuff, continue reading. If that is not your cup of tea, I suggest you just sit back and drink some ginseng and accept that ginseng does wonders to mitochondria health, going right to the core of mitochondria function, and this is why it is considered one of the greatest herbs used. 

Ginsenosides Target Mitochondria, Treating Different Diseases

Some studies have demonstrated that ginsenosides act as protective agents of mitochondrial function, mainly by direct or indirect enhancement of mitochondrial biosynthesis, mitophagy, or electron transport chain (ETC) efficiency or inhibition of mito-ROS. Conversely, ginsenosides also can treat cancer and other diseases by promoting mito-apoptosis and mitophagy. In the models of different diseases, including nervous system disorders, cardiovascular system disorders, and tumors, different ginsenoside monomers cause mitochondrial function alterations by regulating transcription factors, the expression of mitochondria-related genes, and mitochondrial dysfunction pathway networks, which are discussed here.

Neurological Disorders

In the resting state of the human body, the brain consumes 20% of body energy, although it only has 2% of the total body mass. Mitochondrial function can directly influence neuronal function, such as synaptic plasticity, axonal transport, and the release of neurotransmitters, and

abnormal mitochondrial function in neurons precedes neurological changes and neuronal loss. Multiple neurological diseases have been associated with mitochondrial dysfunction, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and ischemic stroke. Ginsenoside monomers can target different functions of mitochondria to preventing and treating neurological disorders.

Cannabis

In 2012, French scientists discovered that mitochondria contain 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. Almost for sure other cannabinoids will also be found to have function here. It turns out that many of the biological processes that involve mitochondria are modulated by endo- and phytocannabinoids. 

There are three major ways that plant and endogenous cannabinoids can directly modulate mitochondrial function:

1. Activating CB1 receptors on the mitochondria
2. Perturbing the mitochondrial membrane
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 (MD) 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.

There is now substantial evidence supporting a role for the ECS in the modulation of energy balance and metabolism. First, various components of the ECS, including the cannabinoid receptors, their endocannabinoid ligands, and those enzymes involved in their synthesis and degradation, have been shown form part of a body-wide communication system. The cannabinoid type 1 (CB1) receptors are widely distributed in the brain and peripheral organs where they regulate cellular functions and metabolism. In the brain, CB1 is mainly localized on presynaptic axon terminals but is also found on mitochondria (mtCB), where it regulates cellular respiration and energy production. Likewise, CB is localized on muscle mitochondria, but very little is known about it.

CB receptors are also distributed in the periphery, e.g., skeletal muscle, liver, pancreas, and adipose tissue, where they are involved in cellular functions and energy metabolism. The function and dysfunction of the endocannabinoid system in muscle is a great focus of research interest to better understand the underlying mechanisms of metabolic disorders.

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 its biphasic function which is related to dosage and length of consumption without a break. 

How are CBD and THC able to balance physiological excess as well as deficiency? Why does a small dose of cannabis stimulate while a large dose tends to sedate? How is it possible that cannabinoid compounds can destroy cancer cells while leaving healthy cells unscathed? Examining the role of mitochondria sheds light on these questions and other perplexing aspects of the endocannabinoid system. You might want to explore this deeper in a separate course at Wild Rose College on Cannabis(  https://wildrosecollege.com/product/cannabis-for-healthcare-providers/  ).

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.” 

Aging, neurodegeneration, metabolic disorders, and cancers are all linked to mitochondrial activity—or lack thereof.

Preclinical studies indicate that THC can inhibit the formation of amyloid plaque in the brain, a hallmark of Alzheimer’s dementia, by enhancing mitochondrial function. And CBD has been shown to stimulate mitochondrial biogenesis and reverse symptoms of memory loss in animals. (The discovery of minimal mitochondrial activity in cancer cells, called the Warburg effect, earned Otto Heinrich Warburg a Nobel prize in 1931.)

Tere is growing evidence that supports an important role for the ECS in regulating the biogenesis, integrity, and oxidative capacity of mitochondria. Collectively, the evidence presented in this review indicates that ECS activation and inhibition can convey detrimental and beneficial effects upon mitochondrial biogenesis and respiratory activity, respectively. Indeed, the studies discussed show that ECS modulation can impact mitochondrial oxidative function in several different ways and through a variety of different mechanisms. However, it may be erroneous to assume that ECS stimulation only leads to mitochondrial dysfunction. Indeed, several studies suggest that cannabinoid receptor activation may also protect against reduced respiratory capacity under certain pathological conditions. Crucially, given the importance of maintaining mitochondrial respiratory capacity in the regulation of energy balance and homeostasis, these studies highlight the potential benefits of therapies aimed at targeting ECS components in order to counteract obesity-induced mitochondrial dysfunction.

Phytocannabinoids have been shown to be able to destroy cancer cells while leaving the healthy cells alone. While these aspects might be expected by those who know the “modulating” or balancing effects of cannabinoids, newer research is revealing how the mitochondria can explain these and other confusing aspects of the ECS. 

In fact, growing evidence suggests that crosstalk 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 crosstalk 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.

Other research suggests that THC can inhibit the formation of amyloid plaques in the brain by enhancing mitochondrial function. Further, CBD has been shown to induce mitochondrial biogenesis and reverse memory loss in animals.

Investigations into CBD’s effect on mitochondria have shed light on how CBD can protect against brain injury by regulating fluctuations in intracellular calcium. These results could be good news for future stroke victims and might suggest that CBD could reduce the severity of ischemic damage (by modulating the activity of intracellular calcium ions). Further, in 2017, a study found that an imbalance of calcium ions in the mitochondria might drive Alzheimer’s disease, further strengthening the connection between the benefits of cannabis and this debilitating disease.

CB1 receptors live right on the surface of the mitochondrial membrane. Interestingly, when the

cell receives a signal from the binding of cell membrane CB receptors, the signal is transmitted

to the mitochondria first and then to the nucleus after. This relationship is instinctive as it acts

largely as the central command and mitochondria acts as the powerhouse behind it. Further, the ECS protects from accelerated aging, protecting the separation of charge to keep our energy currency of ATP pumping out. Mitigating calcium pore formation and leakage of toxic glutamate out of the cell prevents the dysregulated neuronal activity behind the progression of aging in our nerve cells.

In short, keeping our endocannabinoid system in balance supports our energy source that keeps us alive.

Medicinal Mushrooms

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 mushrooms, 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 activate the mitochondria-mediated apoptosis pathway by stimulating the activation of a family of 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.

Reactive Oxygen Species (ROS)-dependent mitochondrial molecular mechanisms underlie antitumor activity of 

polysaccharides in human breast cancer.

Turkey tail mushroom (Coriolus versicolor aka Trametes versicolor) has been shown to dramatically reduce oxidative stress and neuroinflammation in neurodegenerative disorders. By reducing ROS turkey tail mushroom has been shown to downgrade cancer and Alzheimer’s via mitochondria function.

Other Botanicals that Show Some Promise with Mitochondria:

Gotu Kola (Centella asiatica)

This herb is used in both Ayurvedic and Chinese medicine and has been shown to increase mitochondria in brain cells after 2 weeks of consumption in both mice and rats. It was also linked to increasing cognitive function. In a rat model of Parkinson’s disease, gotu kola supplementation for several weeks prevented mitochondrial damage associated with neurotoxicity. The exact effects of gotu kola on mitochondrial function in humans has not been studied, but cognitive improvements have been demonstrated in 48 patients who suffered a stroke. This improvement may be a result of gotu kola’s protective and regenerative effects on the mitochondria, but additional research is needed to show dosage and duration of treatment.  

Gynostemma (Gynostemma pentaphyllum)

Also known as jiaogulan, is a plant found in eastern Asian countries and is used for a variety of health benefits. In obese mice with mitochondrial dysfunction, gynostemma supplementation for 8 weeks improved energy metabolism by increasing mitochondrial proteins (AMPK). Multiple cell studies have found that gynostemma exhibits an antioxidant effect on cells with mitochondrial dysfunction by modifying specific proteins that play a role in mitochondrial activity. 

Chinese Skullcap (Scutellaria baicalensis)

A plant used in traditional Chinese medicine; Chinese skullcap may benefit mitochondrial function. The effects of Chinese skullcap on mitochondria are being investigated in cells. This herb can increase SIRT3, a protein involved in maintaining only normal mitochondria and sensing dysfunctional activity within the cell. In rat cells, Chinese skullcap protected against mitochondrial dysfunction caused by Antimycin A, a component of bacteria. It did so by reducing the free radical formation and promoting the activity of the electron transport chain. We can’t draw any conclusions about the health benefits of Chinese skullcap from cell-based studies.

Danshen (Salvianolic acid A)

Danshen comes from the roots of Salvia miltiorrhiza or red sage. It has been used historically in traditional Chinese medicine. In diabetic rats, danshen treatment for 3 weeks increased the activity of mitochondrial proteins (SIRT3, PGC-1alpha, and AMPK) involved in both the proper functioning of mitochondria and the generation of new mitochondria. In rats with induced ischemic injury (loss of oxygen to tissue), pre-treatment with danshen for 10 days before the injury prevented most mitochondrial dysfunction by acting as an antioxidant. Danshen reduced oxidative damage and therefore improved cognitive function. In heart cells, danshen prevented mitochondrial instability that leads to cell death. More research is needed.  

Caffeic Acid

This is an antioxidant molecule found in many plants. In ischemic (loss of oxygen) rat kidney cells, caffeic acid reduced mitochondrial dysfunction and oxidative damage. Additionally, it improved oxidative phosphorylation and prevented apoptosis caused by the mitochondria. Similar improvements to energy dynamics by the mitochondria were seen in rat liver cells. Human studies are needed.

EGCG (Green tea)

Green tea is notorious for its alleged health benefits. Some scientists believe it can improve mitochondrial function. One of the main active ingredients, epigallocatechin gallate (EGCG), accumulates within the mitochondria and activates several proteins (AMPK and PGC-1alpha) related to mitochondrial function and number. In rats given powdered green tea for 3 weeks, kidney function was restored after injury by improving the number and activity of mitochondrial proteins (PGC-1alpha andSIRT1/3) and increasing mitochondrial DNA levels. 

Curcumin

Curcumin is the active compound found in the spice turmeric. It has many purported health benefits. In the livers and kidneys of diabetic mice, curcumin supplementation for 4 weeks restored mitochondrial function by:

• Increasing ATPase activity 
• Coupling oxygen consumption to energy production 
• Restoring nitric oxide synthesis
• Decreasing blood glucose levels

In rats injected with curcumin for 28 days, increased numbers of mitochondria were observed in skeletal muscle cells after exercise. This was mediated by increased levels of molecules involved in mitochondrial function and activating them (cAMP, AMPK, SIRT1, and PGC-1alpha). Similarly, multiple cell studies suggest that curcumin may:

• Activate AMPK
• Protect against oxidative damage
• Prevent cell death (apoptosis)
• Increase the number of mitochondria
• Improve the efficiency of mitochondrial function

These effects have yet to be explored in animals and humans. 

Berberine

Berberine is a compound found in plants and traditionally used in Western and Chinese medicine. Scientists believeberberine has a direct effect on mitochondrial function. However,

because berberine accumulates in the mitochondria, high doses may be toxic and could induce mitochondrial dysfunction. Additional research is needed. In fish fed high-fat diets, berberine supplementation for 8 weeks improved liver mitochondrial function and prevented cell death. In skeletal muscle cells, berberine prevented mitochondrial dysfunction by increasing

SIRT1 levels and subsequently increased the generation of new mitochondria.

Bitter Melon (Momordica charantia)

Bitter melon is a fruit grown in Asian countries that is a powerful antioxidant. Scientists suggest that bitter melon can induce proteins that increase mitochondrial manufacturing and function (PGC-1alpha and PPAR-alpha) in cells. In rats fed high-fat diets, bitter melon prevented the loss of mitochondrial function by a process known as mitochondrial uncoupling. During uncoupling, the mitochondria produce heat instead of ATP and this results in a loss of energy to the cell. Similar results were seen in mice, where bitter melon supplementation improved mitochondrial function and reduced oxidative stress. Human studies are needed.

Resveratrol

This potent antioxidant is a supplement used for a variety of alleged health benefits. Found naturally in the skin of red grapes, researchers think it might improve mitochondrial function and increase the number of mitochondria per cell.

In a rat model of Parkinson’s disease, resveratrol prevented neurotoxicity by increasing

mitochondrial synthesis and improving mitochondrial function. Similarly, in mice given resveratrol for 15 weeks, resveratrol increased exercise capacity and muscle oxygen consumption. There was also an increase in proteins (SIRT1/PGC-1 alpha/AMPK) that are linked to mitochondrial synthesis and oxidative phosphorylation.

Conversely, resveratrol given to both rats and mice for 8 weeks did not show improvements in mitochondrial function or synthesis. This was attributed to low oral absorption of resveratrol, which may be responsible for the lack of effect seen. In multiple types of cells, resveratrol increased the levels of proteins (SIRT1/PGC-1 alpha/AMPK) involved in manufacturing new mitochondria. Clinical trials about the effects of resveratrol on general and mitochondrial health are needed. Low bioavailability casts doubt on resveratrol’s purported benefits.

Exercise and Physical Activity 

The beneficial effects of regular, non-exhaustive 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. An interesting study published in 2014 also showed exercise can lower the risk of age-related macular degeneration; a separate study, also published in 2014, showed that being sedentary ranks higher than smoking, obesity, or high blood pressure as a risk factor for heart disease. What this latter study would suggest is that a physically active smoker is healthier than a sedentary non-smoker! Yes, exercise is that important.

Cold Exposure

Cold temperatures have a profound effect on the mitochondrial number in animals. Exposing rats to swimming in cold temperatures (23 °C) 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

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 improved 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.

Diet is an important factor in the development of Alzheimer’s disease (AD). Eating the Standard American Diet (SAD), high in saturated and trans-fatty acids as well as low in dietary antioxidants, is quite bad for AD. It can increase levels of aluminum and help to transition metal ions into the blood and brain, both of which are known to cause oxidative damage and consequent neurological damage associated with AD. Poor dietary choices may also lead to inflammation of the brain, which can bring about neurological damage resulting in AD. 

In comparison to the typical American diet, Mediterranean diets have been linked with a slower rate of cognitive decline as well as a reduced risk for cardiovascular illnesses. Numerous prospective studies have shown that Mediterranean diets are associated with lower cognitive decline, decreased risk of progression from mild cognitive impairment (MCI) to AD, lowered risk of developing AD, and even a lower death rate from AD among those already suffering from the disease.

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. 

A version of the ketogenic diet, the KetoFLEX 12/3 diet developed by Dr. Bredesen, has not only been shown to slow down the cognitive decline in mitochondria function, but it has also shown to aid in reversing it in some patients.

Suggested Mitochondria Program

Diet:

• Low simple carbohydrates and high fats, possibly short-term keto diet varied with intermittent fasting – KetoFLEX 12/3 diet.

Exercise:

• Any kind of exercise increases mitochondria, especially soleus pushups (SPU)

Supplementation:

• Glutathione (GSH): Dosage: 200–500 mg per day, best as food
• CoQ_10: Dosage: 100–300 mg per day of regular CoQ₁₀, can cut in half if ubiquinol
• L-Carnitine: Dosage: 400–500 mg per day
• Phosphatidylcholine and Omega-3 Fatty Acid (especially Docosahexaenoic Acid, DHA): Krill as the best source. Dosage: 1000 mg twice a day. 
• Magnesium: Dosage: 300 mg twice a day
• Pyrroloquinoline Quinone (PQQ): Dosage: 10–20 mg daily
• Alpha-Lipoic Acid (ALA): Dosage: 100–300 mg daily
• Vitamin D₃ : Dosage: 1000–3000 IU per day
• NAC (N-Acetyl Cysteine): Dosage: 300–600 mg per day
• Ginseng (Panax ginseng): 1 cup of tea daily
• Cannabis: 25 mg of mixed cannabinols daily, should be customised.
• Medicinal Mushrooms: Reishi, often mixed with others , 2 capsules twice daily

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 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). Care of the microbiome in the gut also plays a huge role here.

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. 

There are numerous options available to those looking to enhance the function of increased energy, Qi, and their mitochondria. While there is no single therapy that can be considered perfect, it has been found that a combination of various therapeutic agents and regular exercise (which should always be included in any mitochondrial regimen) has shown the best results. The use of Soleus pushups has been quite successful. Other areas that are currently being studied include ketogenic diet and intermittent fasting, and we can expect to see some significant findings and recommendations from these studies in the future. It is important to remain open-minded and adapt as needed.

Mitochondrial medicine is a constantly evolving field of study, with new discoveries being made about the beneficial effects of different nutrients and botanicals on our mitochondria every day. While some of these therapies may be more appropriate for individuals with specific health conditions, others have been shown to have overall benefits for improving energy and quality of life. 

So, while there may not be a perfect solution for everyone, we can all take proactive steps towards better energy and quality of life through proper care and maintenance of our mitochondria. Keep learning, keep exploring the possibilities are endless. For sure just sitting in front of a nice fire, around the hearth will warm your winter and bring joy to your health. Your mitochondria will thank you! 

After all, mitochondria are your personal universal Qi translator.

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