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Increase Your ENERGY Source: (Optimizing ATP — Mitochondria)

(The Top 6 Natural Energy Supplements)


The core energy currency of the human body is adenosine triphosphate (ATP), which we produce naturally from healthy mitochondria function.

[References to this Article]

Our mitochondria are the engines of our cells.

In fact, mitochondria create over 90% of the energy to maintain our life, while supporting our major organ function.

Converting our food into energy, mitochondria are the part of the cell responsible for our power.

[Related Article: Supercharge Your Brain, Mood, and Sexual Health with Nitric Oxide]

Responsible for the conversion of carbohydrates and fat into usable energy, our mitochondria is the superstar of our body and bodily processes.

Mitochondria convert the oxygen we breathe into energy.

The primary function of the mitochondria is to produce ATP, the principal source of energy used by all cells.

We use ATP for all cellular activity, as we must eat to replenish ATP production


  1. ATP production, our source of cellular energy.
  2. Removal of old and damaged cells, lowering cellular waste and DNA mutations.
  3. Recycling cellular parts and repairing DNA and other critical structures.
  4. Monitoring cellular calcium levels to coordinate energy production and needs.

Mitochondria use oxygen to produce ATP in creating aerobic or cellular respiration.

This is a reaction using oxygen and producing carbon dioxide, a waste product we exhale through the lungs.


  1. Occurring outside the mitochondria, glycolysis produces some energy, but not nearly enough to meet cellular needs.
  2. Using oxygen in the mitochondria, the Kreb’s or citric acid cycle — (TCA cycle), creates large amounts of energy, involving several phases of chemical processes.
  3. Generating the largest ATP amounts, oxidative phosphorylation is the most critical Kreb’s cycle phase.



  • Mitochondrial dysfunction is linked to hundreds of diseases.
  • If not eliminated, mitochondrial byproducts accumulate, producing free radicals.
  • Oxidative stress is the key cause of virtually all age-related diseases.
  • Free radicals flooding the cells with oxidative stress can cause age-related diseases, leading to the growth of tumor and cancer cells.
  • Genetic mutations can cause metabolic disorders or mitochondrial dysfunction.
  • Mitochondrial or nuclear DNA mutations may be inherited or occur organically.



Researchers believe improving mitochondrial function might be overall directly effective as a target for improving physical and mental health.

Mitochondria are now the target of promising cancer, heart failure, insulin resistance, and neurodegenerative therapies.

Much like methylation and the MTHFR gene, we link mitochondrial dysfunction in many medical conditions.

However, mitochondrial dysfunction is not always the underlying cause or causes of disease.

This means mitochondrial support strategies might not even help improve these diseases.


  • Alzheimer’s Disease
  • Autism
  • Cancer
  • Chronic Fatigue Syndrome (CFS)
  • DNA Damage
  • Diabetes (Type 1 and 2)
  • Fibromyalgia
  • Heart Failure
  • Parkinson’s Disease


  • Bone Issues
  • Cardiomyopathy
  • Developmental Issues
  • Difficulty Exercising
  • Memory Issues
  • Eye Issues
  • Fatigue
  • Gut Issues
  • Hearing Issues
  • Hormonal Issues
  • Infections
  • Kidney and Liver Disease
  • Migraines
  • Movement, Balance, and Coordination (Ataxia)
  • Muscle Pain and Weakness
  • Shortness of Breath
  • Strokes and Seizures
  • Talking Issues
  • Walking Issues


The human genome, comprising all of an individual’s DNA, comes in 23 pairs of chromosomes within the nucleus of the cell.

We refer to this as “nuclear” DNA”.

Nuclear DNA involves proteins we need to activate mitochondrial protein synthesis.

We carry a set of 37 genes we only find in the mitochondria.

Our mitochondrial DNA (mtDNA) is held in a single circular chromosome, with each mitochondrion carrying 2 to 10 chromosome copies.

Mitochondrial DNA involves proteins we needed for mitochondrial function.

We inherit from our parents these 23 pairs of chromosomes in the nucleus, which ultimately makes us “unique” as an individual.

Mitochondrial DNA is inherited from our mother, while mtDNA from our fathers is processed and discarded upon the sperm entering the egg.


Despite no apparent in vivo studies, researchers believe PQQ is the number one mitochondrial booster and often combined in formulas with ubiquinol.

We believe PQQ stimulates mitochondria biogenesis via the cAMP pathway, meaning it causes the cellular growth of mitochondrial mass.

PQQ might be suitable for diseases of mitochondrial dysfunction.

Although its role in humans is unclear, PQQ appears to regulate the expression of genes.

  • Best Mitochondrial and Energy-Stimulating Supplement
  • Cognition
  • Energy
  • Mood and Mental Health
  • Sleep

(Dosage and Use: Typically combined with COQ10 in the ubiquinol form, we see PQQ in dosages from 10 to 20 mg. Many cycle on and off PQQ.)



Similar findings suggest CoQ10, when supplemented in the ubiquinol form, is highly synergistic with PQQ in direct stimulation of mitochondrial biogenesis.

Coenzyme Q10 (CoQ10) is an important compound found in every cell in the body.

As a coenzyme, CoQ10 helps our enzymes work more effectively.

We find CoQ10 is mainly in the membrane of mitochondria, where the body uses it to make energy and antioxidants.

  • Antioxidants
  • Blood Pressure and Blood Sugar
  • Cardiovascular Health
  • Energy
  • Inflammation


(Dosage and Use: Those on statin drugs or individuals over 40 benefits from CoQ10 in the ubiquinol form. The dosage is 100 to 200 mg. As CoQ10 is fat-soluble, it is best taken with meals in divided doses.)



Benfotiamine is a fat soluble vitamin B1 analog, which improves mitochondrial glucose oxidation.

Reversal of reduced glucose oxidation and mitochondrial function is an increasingly desirable goal with global glucose levels on the rise, most notably in those with type 2 diabetes.

[Related Article: Exploring the Power of Benfotiamine and Pantethine]

While technically not a natural supplement, we regard benfotiamine as safe, non-toxic, with little to no side effects.

As we need more studies confirming all claims except for blood sugar benefits, researchers believe benfotiamine may increase ketones in the body.

  • Alzheimer’s Symptoms
  • Blood Sugar
  • Brain Health
  • Diabetes
  • Diabetic Nerve Pain
  • Inflammation and Oxidation
  • Protection from Alcohol Damage
  • Slowing of Cancer Cell Growth

(Dosage and Use: 300 to 600 mg per day in divided doses with meals and sometimes with Alpha Lipoic Acid is the believed dosage.)



Water-soluble vitamin B5 analog, pantethine improves lipid metabolism, in two ways: (1) increasing coenzyme A, (CoA) levels, profoundly lowering cholesterol and triglycerides, and by (2) modulating the activity of hydroxy-methyl-glutaryl-coenzyme A reductase.


[Related Article: Improving Cholesterol without Drugs]


This means to say, pantethine is a potent cholesterol weapon and offers a non-toxic, safe alternative to statin medications.

It appears to show strong synergy with benfotiamine, and also appears to increase both ketones in the body and glutathione, (GSH).

  • Athletic Performance
  • Cardiovascular Disease and Risk of Death
  • Cystinosis
  • Gastrointestinal Health
  • HDL Cholesterol
  • LDL Cholesterol
  • Immune Health
  • Lipid Peroxidation
  • Total Cholesterol
  • Triglycerides

(Dosage and Use: We see 300 mg in use in studies, three times daily. We often see it in combination with benfotiamine.)


As a naturally occurring sugar in our cells, D-ribose is a critical component in most of our biological pathways, with its most action involving glycation, the bonding between sugar, protein, or fat molecules.

Acting as the primary structural basis of RNA and DNA, D-ribose, along with adenine, comprises adenosine molecule of adenosine triphosphate (ATP).

D-ribose also makes flavin adenine dinucleotide (FAD), and nicotinamide adenine dinucleotide (NAD), our two cellular respiration molecules.

Effective in influencing the recovery of these energy molecules, D-ribose as a naturally occurring ATP supplement is a widely popular gym and athletic performance supplement.

Some cardiologists believe D-ribose is protective of the heart prior to, during, and after a cardiac event.

  • Athletic Performance
  • Chronic Fatigue
  • Fibromyalgia
  • Heart Disease

(Dosage and Use: 5 to 15 grams in divided doses. Many are combining D-Ribose with Creatine.)


Also marketed as a popular gym supplement, creatine in multiple cellular studies both in vitro and in vivo, is effective in restoring mitochondrial function, protecting against structural damage and oxidative stress, and reducing the overall impact of mitochondrial DNA mutations.

We believe creatine to be synergistic with D-ribose.

Creatine normally acts as a reserve for ATP by forming a compound called creatine, phosphate, or phosphocreatine.

When cellular demand for ATP is excessive, its mitochondria can produce creatine and release phosphate, (the “P” in ATP) to enhance the ATP supply.

In fact, creatine phosphate typically provides the initial burst of ATP required for strenuous muscle activity.

Recent evidence believes creatine is effective for depression and may be effective for dementia, testosterone, and brain protection.

  • Athletic Performance
  • Cognition
  • Energy
  • Focus
  • Mood and Mental Health
  • Muscle Strength

(Dosage and Use: The average daily creatine user takes 5 grams per day. We find vegans and females to have lower creatinine levels. Using micronized brands is optimal to avoid side effects. Creatine is often in combination with D-Ribose.)




Niacinamide might improve mitochondrial cellular quality by causing dysfunctional mitochondria to fragment, (autophagy).

As the precursor to NAD, niacinamide, (No flush vitamin B3), niacinamide may improve mitochondrial cellular quality, while at the same time stimulating cellular division of dysfunctional cells.

We see this effect was in human cells, reducing mitochondrial levels but increasing the function of healthy mitochondria.

(Dosage and Use: Many believe niacinamide is superior to niacin as a NAD precursor. One should avoid niacin products saying delayed, extended, or sustained release. We believe low to moderate 250 mg to 500 mg, three times daily dosages to be optimal.)


Magnesium, the second most abundant chemical element in our cells, is critical for many core cellular processes, forming many compounds including enzymatic reactions, ion channel functions, metabolic cycles, cellular signaling, and DNA/RNA stabilities.

Proven magnesium levels are essential in the homeostasis of intracellular, physiologically attributed growth, proliferation, differentiation, energy metabolism, and overall cellular health.)

In multiple cellular studies, the amino acid NAC and precursor to glutathione, (GSH), shows potent effects on mitochondrial function and oxidative stress.

NAC is so effective, we consider it an essential medicine in hospitals worldwide.

(Dosage and Use: We don’t likely know the dosage and many suggest it could be 250 to 500 mg, three times daily. If possible, it might be better absorbed on an empty stomach like any other amino acid.)


We find malic acid, the sour organic compound called alpha hydroxy acid (AHA), in many fruits.

Our bodies also produce malic acid, which creates energy powering our cells from malate.

Popular in the exercise and fibromyalgia communities, malic acid is used for energy, fatigue, strength, and endurance during exercise and most likely increases mitochondrial pathway function.

Large-scale studies should be able to replicate these findings.

(Dosage and Use: A popular mitochondria supplement is magnesium-malate. We see dosages of 600 to 800 mg as being the possibly effective malic acid amount. Oral sprays are also used and taken throughout the day.)


ALCAR, acetyl-l-carnitine, is another popular amino acid supplement.

Despite a lack of evidence, many view ALCAR as a mitochondrial supplement claiming it improves aging, blood vessels, and cognitive decline.

Proponents of ALCAR suggest it improves cellular death (apoptosis), mitochondrial generation, and oxidative stress while improving mitochondrial proteins.

In animal studies, we see ALCAR delivering protective benefits to the liver and kidneys.

(Dosage and Use: Up to 3,000 mg in 3 daily divided doses. Also, better when taken on an empty stomach.)


Often used with benfotiamine for blood sugar and diabetic issues, alpha-lipoic acid is a naturally occurring substance necessary for energy production via a process we call glycolysis.

Lipoic acid reduces age-associated mitochondrial dysfunction and is considered a mitochondrial supplement.

In animals, alpha-lipoic acid reduces mitochondrial DNA damage, improving the antioxidant activity of the mitochondria, while increasing the mitochondria cell count.

We see an improvement in mitochondrial function through the activation of the metabolic regulating and anti-cancer acting SIRT1/3 protein.

(Dosage and Use: Only the R-form is bioavailable. This means whereas only 50% of ALA is used, the body can use 100% of R-ALA. Dosages range widely in excess of 10 grams, depending on the condition, whereas the average daily dose is less than 1 gram.)


We believe nicotinamide riboside to have a very similar function to niacinamide, (vitamin B3), with its actions as a precursor to NAD+.

Contrasting vitamin B3, oral supplementation of NAD+ metabolites, nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), increases levels of NAD+, improving multiple physiological functions in animal models.

(Dosage and Use: This remains unclear. Follow us for updates as they unfold. Expect to hear more about this combination in time.)

Apigenin, Berberine, Beta-Alanine, Bitter Melon, Butyrate, Caffeic Acid, Chinese Skullcap, Curcumin, Danshen (Red Sage), ECGC (Green Tea), Gotu Kola, Gynostemma, Beta-Hydroxy Beta-Methyl Butyric Acid HMB, Hydroxytyrosol, Inosine, L-Carnitine, Luecine, MitoQ, Niacin B3, Oxaloacetate, Piracetam, Potassium, Pterostilbene, Resveratrol, Succinic Acid, Taurine, TMG, Vitamin B1, Vitamin B2, Vitamin B5, Vitamin B6, Vitamin B9, Vitamin B12, Vitamin C, Vitamin E, Methylene Blue.


As always, we need to consider the role of our lifestyle.

We believe the FOUR following lifestyle strategies can lead to healthy mitochondria function: (See Previous Articles on These)

  1. Cold Exposure (Cold Showers)
  2. Exercise (HIIT)
  3. Intermittent Fasting
  4. Ketogenic Diets*

*(Or no/ low processed sugar or complex over simple carbs)

We next need to consider coverage of key micronutrients such as B-vitamins, C, D3, E, K2, magnesium, omega-3’s, and others.

For the top overall mitochondrial support combination, PQQ with Ubiquinol appears to stand at the top of the charts.

For those with metabolic issues and or wanting to improve blood sugar and fat, combining pantethine with benfotiamine makes the most sense.

For the gym, sports, and overall energy, taking micronized creatine with D-ribose can be a winning game plan. (My favorite combination).

Based on extensive studies, it is our firm conclusion for both mitochondrial support and a wide array of other essentials, vegans should consider creatine supplementation as an essential supplement.

What did you think of this review?

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What’s your favorite mitochondrial supplement?

Your Friend in Health

Mark Stein

[Get The Essential 3 Sugars and Fat for Every Health Optimizer]