The mitochondria are commonly known as the “powerhouse” of the cell, but energy production is only one of the critical roles played by these organelles. This is why mitochondrial dysfunction tends to have many different signs and symptoms, causing practitioners to chase the wrong things. In fact, the average person with a disorder of the mitochondria will see at least 8 doctors before being properly diagnosed.

Dr. Bryan Walsh, ND is with me today to take an in-depth look at how the mitochondria operate and their roles in the body.  We discuss free radicals and antioxidants (hint - those supplements don’t do what we think they do!). Bryan describes mitochondrial dysfunction - what causes it, how to assess for it, and what can happen when it goes untreated. If you want to take a deep dive into this subject, go take Bryan’s new course, Everything You Ever Wanted to Know About the Mitochondria - an amazing 16-hour training for practitioners and biochemistry enthusiasts.

[00:03:30] Patients seeing an average of 8.19 doctors before getting diagnosis; Study: Grier, Johnston, et al. "Diagnostic odyssey of patients with mitochondrial disease: Results of a survey." Neurology Genetics 4.2 (2018): e230.

[00:04:20] Functions of mitochondria.

[00:07:22] Systemic problems; widespread hormonal effects.

[00:08:10] Signs of mitochondrial dysfunction.

[00:10:44] STEM-Talk podcast Episode 67: Doug Wallace talks about mitochondria, our human origins and the possibility of mitochondria-targeted therapies.

[00:11:30] Podcasts: How to Track Effectively and The Ideal Weight Program with Dan Pardi.

[00:13:46] Khan Academy.

[00:14:05] Insulin resistance as cellular antioxidant defense mechanism; Study: Hoehn, Kyle L., et al. "Insulin resistance is a cellular antioxidant defense mechanism." Proceedings of the National Academy of Sciences(2009): pnas-0902380106.

[00:16:47] Antioxidants.

[00:20:01] Poor outcomes associated with antioxidant supplementation; Studies: 1, 2, 3, 4, 5.

[00:20:39] Ben Goldacre.

[00:24:22] How mitochondria work; Free radicals.

[00:26:47] Podcast: How Oxidative Stress Impacts Performance and Healthspan, with Megan Roberts.

[00:27:32] Blood markers of oxidative stress: Bilirubin, GGT, Uric Acid.

[00:29:05] GGT as a marker of oxidative stress; Study: Lee, Duk-Hee, Rune Blomhoff, and David R. Jacobs. "Review is serum gamma glutamyltransferase a marker of oxidative stress?." Free radical research 38.6 (2004): 535-539.

[00:29:11] GGT as a marker of xenobiotic exposure; Study: Lee, Duk-Hee, and David R. Jacobs Jr. "Is serum gamma-glutamyltransferase a marker of exposure to various environmental pollutants?." Free radical research 43.6 (2009): 533-537.

[00:29:16] GGT as a marker of glutathione deficiency in the liver; Study: Koenig, Gerald, and Stephanie Seneff. "Gamma-glutamyltransferase: a predictive biomarker of cellular antioxidant inadequacy and disease risk." Disease markers 2015 (2015).

[00:30:00] Bilirubin 0.4 or below associated with all-cause mortality; Study: Ong, Kwok-Leung, et al. "The relationship between total bilirubin levels and total mortality in older adults: the United States National Health and Nutrition Examination Survey (NHANES) 1999-2004." PLoS One 9.4 (2014): e94479.

[00:31:35] Study: Siems, Werner G., et al. "Uric acid and glutathione levels during short-term whole body cold exposure." Free Radical Biology and Medicine 16.3 (1994): 299-305.

[00:32:20] Uric acid and the ketogenic diet.

[00:37:01] Causes of mitochondrial dysfunction.

[00:39:02] Nutrient deficiencies; Study: Ames, Bruce N., Hani Atamna, and David W. Killilea. "Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging." Molecular aspects of medicine 26.4-5 (2005): 363-378.

[00:43:26] Infections.

[00:43:41] Do Mitochondria Have An Immune System? Study: Popkov, V. A., et al. "Do mitochondria have an immune system?." Biochemistry (Moscow) 81.10 (2016): 1229-1236.

[00:43:54] Theory: Mitochondria as bacteria.

[00:45:06] Bacteria, viruses target mitochondria; Studies: Lobet, Elodie, Jean-Jacques Letesson, and Thierry Arnould. "Mitochondria: a target for bacteria." Biochemical pharmacology 94.3 (2015): 173-185, and D Williamson, Chad, Roberta L DeBiasi, and Anamaris M Colberg-Poley. "Viral product trafficking to mitochondria, mechanisms and roles in pathogenesis." Infectious Disorders-Drug Targets (Formerly Current Drug Targets-Infectious Disorders) 12.1 (2012): 18-37.

[00:45:50] Podcast: Everything You Wanted to Know about Detoxification, with Bryan Walsh.

[00:45:52] Walsh detox protocol; Elite Performance Program.

[00:46:17] Mitochondria as a target of xenobiotic exposure; Study: Meyer, Joel N., et al. "Mitochondria as a target of environmental toxicants." toxicological sciences 134.1 (2013): 1-17.

[00:47:26] 35% of pharmaceuticals tested caused mitochondrial dysfunction; Studies: Dykens, James A., and Yvonne Will. "The significance of mitochondrial toxicity testing in drug development." Drug discovery today 12.17-18 (2007): 777-785, and Meyer, Joel N., and Sherine SL Chan. "Sources, mechanisms, and consequences of chemical-induced mitochondrial toxicity." (2017): 2-4.

[00:48:59] Classes of medications that cause dysfunction.

[00:49:20] Absence of exposure to physical stressors.

[00:52:08] Hormetea; Podcast: Hormesis, Nootropics and Organic Acids Testing.

[00:53:37] Book: Why Buddhism is True: The Science and Philosophy of Meditation and Enlightenment, by Robert Wright.

[00:57:12] Resveratrol study: Kjær, Thomas Nordstrøm, et al. "No beneficial effects of resveratrol on the metabolic syndrome: a randomized placebo-controlled clinical trial." The Journal of Clinical Endocrinology & Metabolism 102.5 (2017): 1642-1651. From our Highlights email series.

[00:57:13] Appropriately applied stress in the right amount.

[00:58:10] Dietary interventions.

[00:58:27] Ketogenic, low carb, calorie restriction, time restricted feeding; Study: Vidali, Silvia, et al. "Mitochondria: The ketogenic diet—A metabolism-based therapy." The international journal of biochemistry & cell biology 63 (2015): 55-59.

[00:59:47] Therapeutic uncoupling; protonophore.

[01:02:27] 2,4-Dinitrophenol (DNP).

[01:05:33] DNP mouse study: Perry, Rachel J., et al. "Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats." Science 347.6227 (2015): 1253-1256.

[01:07:21] Curcumin.

[01:08:56] Podcast: A Guide to Flawed Studies with Richard Feinman. Cartoon: The car analogy of metabolic inhibitors.

[01:10:37] Metabolic Fitness Pro.

[01:11:40] Course: Everything You Ever Wanted to Know About the Mitochondria.