Fire Up Your Mitochondria For Energy and Health

Remember those mitochondria…those little energy powerhouses within the cells that you studied in Biology? Well, those tiny cellular parts consume about 90% of the oxygen used by the body for oxidative phosphorylation, the process used to make ATP from the foods we eat [i]. ATP or adenosine triphosphate is the primary energy carrier within our cells making most of our energy needs. It should be no surprise that the heart and the brain are organs with the highest energy requirements. When we don’t have enough ATP or when they are not functioning well, we can experience a variety of diseases or symptoms. Mitochondria are fundamental to life and health. [ii]

The essential keys to mitochondrial function are oxygen, magnesium, and CoQ10. B vitamins are also required for their relationship to enzyme functions in the citric acid cycle, carbohydrate and fat metabolism.[iii] Oxygen serves as the ultimate electron receptor from the electron transport chain, allowing ATP to be generated by the mitochondria. When there is not enough oxygen, the result is the decreased ATP.

Damaged mitochondria also cannot produce sufficient ATP for the energy needs of the body which may impact the liver, heart, and muscle tissue. The greatest number of mitochondria are in muscle tissue. As mitochondria are central regulators of the aging process in the heart and skeletal muscle, a decline in mitochondrial content and function plays a major role in aging heart and skeletal muscle which contributes to the development of cardiac dysfunction or muscle loss (sarcopenia).[iv]

Mitochondrial dysfunction occurs in many diseases. This is when mitochondria are not working well. Manifestations of mitochondrial dysfunction are complex and poorly understood.[v] There are primary inherited genetic mitochondrial diseases (PMD) where the mitochondrial DNA is dysfunctional through inherited DNA. Genetic mitochondrial disease can affect the heart, liver, brain, kidneys, eyes, ears, pancreas, or overall growth and development and are clinically diagnosed and confirmed with testing mitochondrial DNA and other clinical testing. Inherited mitochondrial dysfunction may be related to autism, seizure disorders, learning disabilities, pancreatic failure, diabetes, pain, heat/cold intolerance, hypotonia, parathyroid failure, autism, cardiomyopathy, and other conditions. One resource is the United Mitochondrial Disease Foundation. 

Mitochondrial dysfunction also occurs when the mitochondria don’t work as well as they should due to another disease or condition. These are secondary mitochondrial dysfunctions (SMD) which may be either inherited or acquired and the diagnosis is complicated as there is much overlap with PMD signs and symptoms.[vi] Secondary dysfunctions may affect diseases, including Alzheimer’s disease, muscular dystrophy, obesity, Lou Gehrig’s disease, diabetes, cancer, and others.

Unfortunately, these little energy powerhouses are often destroyed and we are not aware until we ultimately experience disease or symptoms. So, how do you know that your mitochondria are not functioning well? Well here are some signs and symptoms of mitochondrial dysfunction:

• Overweight
• Cardiovascular issues
• Chronic Fatigue
• Brain Fog
• Pain such as migraines (see my blog on migraines here)
• Depression
• Toxin Exposure
• Chronic stress
• Seizures
• Strokes
• Significant developmental delays
• Heart and kidney issues
• Speech issues
• Sight issues
• Digestion Issues

What causes mitochondrial dysfunction?

• Chronic inflammation-This can be due to things like oxidative stress, diet, pathogens, or detoxification issues.
• Chronic Stress-Emotional or environmental stress can change how ATP is produced and the mitochondria instead of going through the normal citric acid cycle to produce ATP goes through the Cori cycle, resulting in a net loss of ATP. This is why many people under stress feel fatigued because their mitochondria produce less energy. Stress results in anaerobic metabolism and the build-up of lactate, which is inefficient energy production. Aerobic metabolism is the best way to avoid lactic acid buildup and promote normal physiology through the citric acid cycle. Too much anaerobic results in lactate buildup.
• Toxins-Exposure to pesticides, smoke, chemicals whether occupational or even in self-care products such as cosmetics and lotions. Glyphosate has been linked to mitochondrial disease. [vii]
• Detoxification Issues-Mitochondria support kidney detoxification. The kidney is only secondary to the heart in terms of number of mitochondria and it is thought that mitochondrial homeostasis can prevent or help with progression of kidney disease. [viii] Mitochondria help regulate liver function. When detoxification is impaired with liver disease from chronic alcoholism or non-alchoholic fatty liver disease, mitochondrial dysfunction also occurs.
• Leaky gut- Dysbiosis of the gut microbiota and mitochondrial dysfunction are associated with chronic intestinal inflammation in cancer and irritable bowel disease (IBD). [ix]
• Medications-Tryptophan is depleted with SSRI therapy, which can increase anxiety. Tryotophan is required to make serotonin. Drugs such as antibiotics, aspirin, AZT, cocaine, grisepfulvin, indomethacin, methamphetamine, l-DOPA, NSAIDs, propofol, statins, doxoribucin, risperidone, and acetaminophen can impact mitochondrial function as well as others.[x]
• Nutrient Deficiencies-Depletion of key nutrients such as magnesium and glutathione.
• Oxidative stress-accumulation of free radicals and less energy production. This can be due to over-exercise, toxins, pathogens, heavy metal accumulation, acute infection. Oxidative stress can lead to premature aging and disease. Oxidative stress and mitochondrial dysfunction are linked to many neurogenerative diseases such as Alzheimer diseases, Amyotrophic lateral sclerosis, Friedreich’s ataxia, Huntington’s disease, Multiple sclerosis, and Parkinson’s diseases.[xi]
• Insulin Resistance: High glucose and diabetes is associated with mitochondrial dysfunction. [xii]
• Acid-Alkaline Balance issues-Lactic acid build up and a chronic metabolic acidosis have been associated with mitochondrial dysfunction and chronic diseases such as diabetes.

Ways to fire up your mitochondria:

• Breathing Exercises: There are a variety of breathing exercises such as box breathing or the 4,7,8 method that can support oxygenation to your tissues and decrease stress.
• Diet:
  • Eating the right diet and amount of macronutrients (carbs,7, 8 fats, proteins) for your body type. I do Metabolic Typing® as part of my coaching packages. Metabolic typing identifies each person’s fundamental metabolic level and macronutrient diet allowing for increased energy, weight loss, and greater disease resistance. The right amount of fats, proteins, and carbs are the first line in addressing energy production issues.
  • A short-term ketogenic diet with exercise was shown to improve skeletal muscle and mitochondrial function for insulin-resistant patients. [xiii] For some individuals, who may have insulin resistance, a ketogenic diet may be indicated short-term.
  • A diet rich in proanthocyanidins such as found in grapes, pomegranates, apples, and red fruits may help as nutraceuticals in the management of chronic illnesses associated with mitochondrial function.[xiv]
  • A diet high in astaxanthins which is found in aquatic animal foods such as salmon, trout, shrimp and lobster provides anti-oxidants shown to reduce oxidative stress and improves mitochondrial function. [xv]
  • Citrus fruits contain bioflavonoids which are important regulators of mitochondrial function.
• Digestion-Adequate digestion and absorption of carbs, protein, and fats (macronutrients) are also important. Many people have inadequate digestion or absorption and may need support with digestive enzymes.
• Supplementation: Based on a lab test called an organic acids test (OAT), support of mitochondrial production and function may be needed with either or both amino acids and specific mitochondrial support. Dr. Dan Kalish reviewed nutrients to increase mitochondrial production that is contained in products such as Mitochondrial NRG™ which are listed below in addition to others:[xvi] Based on whether the mitochondrial markers on the test, different supplements may be recommended depending on whether the markers are high or low. The role of micronutrient support for mitochondrial function for critically ill patients is emerging and it will be important to understand the interplay of specific micronutrients.[xvii]  

Below are examples of potential natural supplements for mitochondrial dysfunction. Many of these have been used by functional practitioners.[xviii] As always, these should be taken with supervision by your medical provider. For individuals who have PMD, the National Institute of Health (NIH) provides recommendations for health professionals for these disorders.

• Alpha Lipoic Acid (ALA): ALA may be beneficial for Alzheimer’s Disease and other diseases of mitochondrial dysfunction as it promotes mitochondrial homeostasis and supports an anti-oxidant response. [xix]
  • Ribose: D-ribose is a naturally occurring monosaccharide found in the cells’ mitochondria and is essential in energy production. It has been used to treat mitochondrial dysfunction.[xx]
  • B Vitamins: Vitamins B1, B2, B6, niacin, biotin, folic acid and pantothenic acid are important for metabolic pathways in mitochondrial respiration and energy production. Pantethine is stable form of the active form of vitamin B5 or pantothenic acid. Pantothenic acid is key to transport of fats within cells and energy-producing mitochondria. It is a critical component of an enzyme called coenzyme CoA. Without it, fats could not be metabolized to energy.
  • Magnesium: Mitochondrial magnesium regulates the cellular energy status, changes mitochondrial morphology, and affects cell vulnerability against biological stress.[xxi]
  • Manganese: This is a trace element and most of it is contained within our mitochondria where it serves to activate a number of enzymes. It is especially critical to anti-oxidant enzyme systems within the mitochondria.[xxii]
  • Resveratrol: resveratrol is a powerful mitochondrial nutrient that can fight fatigue, memory loss, and metabolic dysfunction but higher doses are not necessarily better.[xxiii]
  • Glutathione: Glutathione which is a powerful anti-oxidant or substances such as N-acetyl cycteine (NAC) which increase glutathione production help address free radicals produced within the body.
  • Coenzyme Q10 (CoQ10 or also called ubiquinone):CpQ10 has been used widely for mitochondrial function. This enzyme works directly within the mitochondria to support function and supplementation has positive anecdotal evidence along with little toxicity.[xxiv]^{, [xxv]}
  • Free Form Amino Acids: Free form amino acids may be recommended for hypometabolic conditions as they stimulate mTOR, a central regulator of metabolism. As a precaution, when used long-term can be carcinogenic and should only be used when clinical and laboratory evidence indicates metabolic slowdown.
  • Selenium: Selenium is required for mitochondrial biogenesis.
• Exercise: Increase muscle mass with exercise. The right amount of exercise and not over-exercise is important, particularly with those people with chronic stress. Exercise plus resveratrol was shown to improve physical function as measured by citrate synthase, a measure of skeletal muscle mitochondrial function.[xxvi]
• Sunlight: Get 15 minutes of sunlight daily to get enough vitamin D. Mitochondria also capture the energy from sunlight from the intake of food. Vitamin D has been shown to be important in mitochondrial function through regulating respiratory activity, protection from oxidative damage and preserving mitochondrial integrity and cell survival.[xxvii]
• Heat/Cold Therapy: Heat therapy may increase mitochondria in muscle tissue.[xxviii] Cold therapy using cold showers at the end of a warm shower and ice baths have become popular through with Wim Hof and his methods to increase energy. 
• Red Light Therapy: Mitochondrial photostimulation has been shown to increase ATP production.[xxix] Red light has been used to reduce inflammation, reduce pain and stimulate healing, one of the mechanisms being cytochrome c oxidase in mitochondria. [xxx]
• Stress Management: Support positive emotions with medication, relaxation techniques, guided imagery, or tapping. I provide a coaching program to help deal with toxic emotions, using the emotional freedom technique (EFT), otherwise known as tapping.
• Sleep/Rest: Go to bed by 10P and get up by 7 AM to keep your sleep pattern consistent with day and night. Impaired sleep rhythms have been associated with mitochondrial dysfunction and circadian patterns has been shown to set the rhythm for mitochondria. [xxxi]
• Protection from Oxidative Stress: Adequate antioxidants to protect against free radicals.
• Intermittent Fasting: When fasting, During ketogenesis, fatty acids are broken down in the mitochondria of cells by a process called beta-oxidation and converted to the ketones acetoacetate and beta-hydroxybutyrate. These ketones are used by muscle cells and neurons (brain cells) to generate ATP used to fuel cellular processes.
• Pathogens-Gut pathogens as a result of dysbiosis and leaky gut may be a root cause of dysfunction and need to be corrected.
• Water-Adequate water intake is needed to support digestion and the chemical breakdown of food and production of ATP.

Ways to test for mitochondrial dysfunction: Did you know that you can actually measure your mitochondrial function? An organic acid test, known as an OATS test can measure mitochondrial function as well as toxin build-up and oxidative stress which is an indicator of mitochondrial damage. Most organic acids are intermediate or end-stage metabolism of energy production. High levels of intermediates indicate nutrient deficiencies, especially CoQ10, magnesium, carnitine, and B vitamins. Low OAT markers most often mean that the Cori cycle is making ATP instead of the citric acid cycle.  The amount of damage to the mitochondrial DNA can also be estimated by 8-OHdG in the urine. 

At Peace x Piece Wellness Coaching, both OAT testing and urinary 8-OHdG are available as well as gut pathogen and cortisol (stress hormone) testing.  While Peace x Piece Wellness Coaching does not diagnose mitochondrial disease or dysfunction, the main goal with symptoms of mitochondrial dysfunction is to use labs to reveal hidden cues of mitochondrial dysfunction. The main focus is to rebalance the body with diet, rest, exercise, stress management, and supplementation through coaching. So, learn how you can fire up those mitochondria to feel better, move better, and live better. Find out more through a free discovery call.

References:

---

[i] Kalish, Dan. https://www.youtube.com/watch?v=Xz8sUXVt7Ac, May 26, 2016. The Kalish Institute.

[ii] Pizzorno J. Mitochondria-Fundamental to Life and Health. Integr Med (Encinitas). 2014;13(2):8-15.

[iii] Kalish, Dan. Supporting Mitochondrial Function: Fatigue and Metabolic Issues Revealed by Organic Acid Testing. https://www.youtube.com/watch?v=Jlc9BsBza_A. March 24, 2021. The Kalish Institute and Genova Diagnostics.

[iv] Boengler K, Kosiol M, Mayr M, Schulz R, Rohrbach S. Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue. J Cachexia Sarcopenia Muscle. 2017;8(3):349-369. doi:10.1002/jcsm.12178.

[v] Niyazov DM, Kahler SG, Frye RE. Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment. Mol Syndromol. 2016;7(3):122-137. doi:10.1159/000446586

[vi] Fernandes, Joana. Distinguishing Between Primary and Secondary Mitochondrial Disease Important for Diagnosis, Treatment. https://mitochondrialdiseasenews.com/2016/09/16/distinction-between-primary-secondary-mitochondrial-disease-important-diagnosis-treatment/. Sept 16, 2016.

[vii] Swanson, Nancy L. Hoy, Judy, Seneff, Stephanie. https://www.researchgate.net/profile/Nancy-Swanson-2/publication/299532136_Evidence_that_glyphosate_is_a_causative_agent_in_chronic_sub-clinical_metabolic_acidosis_and_mitochondrial_dysfunction/links/57acafaa08ae7a6420c30b30/Evidence-that-glyphosate-is-a-causative-agent-in-chronic-sub-clinical-metabolic-acidosis-and-mitochondrial-dysfunction.pdf. International Journal of Human Nutrition and Functional Medicine,  2016, http://www.ichnfm.org/. 

[viii] Duann P, Lin PH. Mitochondria Damage and Kidney Disease. Adv Exp Med Biol. 2017;982:529-551. doi:10.1007/978-3-319-55330-6_27.

[ix] Jackson DN, Theiss AL. Gut bacteria signaling to mitochondria in intestinal inflammation and cancer. Gut Microbes. 2020;11(3):285-304. doi:10.1080/19490976.2019.1592421

[x] Orsucci D, Ienco EC, Siciliano G, Mancuso M. Mitochondrial disorders and drugs: what every physician should know. Drugs Context. 2019;8:212588. Published 2019 Jul 4. doi:10.7573/dic.212588

[xi] Islam MT. Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res. 2017;39(1):73-82. doi:10.1080/01616412.2016.1251711

[xii] Dassanayaka S, Readnower RD, Salabei JK, et al. High glucose induces mitochondrial dysfunction independently of protein O-GlcNAcylation. Biochem J. 2015;467(1):115-126. doi:10.1042/BJ20141018

[xiii] Miller VJ, LaFountain RA, Barnhart E, et al. A ketogenic diet combined with exercise alters mitochondrial function in human skeletal muscle while improving metabolic health. Am J Physiol Endocrinol Metab. 2020;319(6):E995-E1007. doi:10.1152/ajpendo.00305.2020

[xiv] Rigotti M, Cerbaro AF, da Silva IDR, et al. Grape seed proanthocyanidins prevent H2 O2 -induced mitochondrial dysfunction and apoptosis via SIRT 1 activation in embryonic kidney cells. J Food Biochem. 2020;44(3):e13147. doi:10.1111/jfbc.13147

[xv] Kim SH, Kim H. Inhibitory Effect of Astaxanthin on Oxidative Stress-Induced Mitochondrial Dysfunction-A Mini-Review. Nutrients. 2018; 10(9):1137. https://doi.org/10.3390/nu10091137. https://www.mdpi.com/329950.

[xvi] Kalish, D. https://kalishinstitute.com/blog/mitochondrial-nrg-supplement-video/. The Kalish Institute.

[xvii] Wesselink E., Koekkoek W.A.C., Grefte S., et al. Feeding mitochondria: Potential role of nutritional components to improve critical illness convalescence. Clinical Nutrition,  Vol. 38, (3), P982-995, June 01, 2019. https://www.clinicalnutritionjournal.com/article/S0261-5614(18)32426-9/fulltext.

[xviii] Nicolson GL. Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements. Integr Med (Encinitas). 2014;13(4):35-43.

[xix] Sávio Monteiro dos Santos, Camila Fernanda Rodrigues Romeiro, Caroline Azulay Rodrigues, Alícia Renata Lima Cerqueira, Marta Chagas Monteiro, “Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer’s Disease?”, Oxidative Medicine and Cellular Longevity, vol. 2019, Article ID 8409329, 14 pages, 2019. https://doi.org/10.1155/2019/8409329

[xx] Mahoney DE, Hiebert JB, Thimmesch A, et al. Understanding D-Ribose and Mitochondrial Function. Adv Biosci Clin Med. 2018;6(1):1-5. doi:10.7575/aiac.abcmed.v.6n.1p.1

[xxi] Yamanaka R, Tabata S, Shindo Y, et al. Mitochondrial Mg(2+) homeostasis decides cellular energy metabolism and vulnerability to stress. Sci Rep. 2016;6:30027. Published 2016 Jul 26. doi:10.1038/srep30027

[xxii] Holley AK, Bakthavatchalu V, Velez-Roman JM, St Clair DK. Manganese superoxide dismutase: guardian of the powerhouse. Int J Mol Sci. 2011;12(10):7114-7162. doi:10.3390/ijms12107114

[xxiii] Leaf, Alex. Resveratrol For Mitochondria, Brain, And Heart Health. https://theenergyblueprint.com/resveratrol-alex-leaf/.

[xxiv] Mancuso M, Orsucci D, Filosto M, Simoncini C, Siciliano G. Expert Opin Pharmacother. 2012 Mar; 13(4):527-43.

[xxv] Díaz-Casado ME, Quiles JL, Barriocanal-Casado E, et al. The Paradox of Coenzyme Q10 in Aging. Nutrients. 2019;11(9):2221. Published 2019 Sep 14. doi:10.3390/nu11092221

[xxvi] Harper SA, Bassler JR, Peramsetty S, et al. Resveratrol and exercise combined to treat functional limitations in late life: A pilot randomized controlled trial. Exp Gerontol. 2021;143:111111. doi:10.1016/j.exger.2020.111111

[xxvii] Ricca C, Aillon A, Bergandi L, Alotto D, Castagnoli C, Silvagno F. Vitamin D Receptor Is Necessary for Mitochondrial Function and Cell Health. Int J Mol Sci. 2018;19(6):1672. Published 2018 Jun 5. doi:10.3390/ijms19061672.

[xxviii] https://www.sciencedaily.com/releases/2018/07/180731092029.htm. Science Daily. From the Journal of Applied Physiology, July 31, 2018.

[xxix] Tafur J, Mills PJ. Low-intensity light therapy: exploring the role of redox mechanisms. Photomed Laser Surg. 2008;26(4):323-328. doi:10.1089/pho.2007.2184

[xxx] Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys. 2017;4(3):337-361. doi:10.3934/biophy.2017.3.337

[xxxi] https://www.sciencedaily.com/releases/2018/03/180306093116.htm. Our circadian clock sets the rhythm for our cells’ powerhouses. Science Daily, March 6, 2018.

---