As functional medicine clinicians, our primary goal is to optimize patient health and well-being using a root cause approach. A vital component to achieve this is understanding the intricate mechanisms contributing to cellular energy production.
Mitochondrial Dysfunction: Fatigue and Beyond
Mitochondria, the powerhouses of our cells, are essential for generating energy. As such, mitochondrial dysfunction can result in excess fatigue as well as other symptoms that are common to almost every chronic disease. Mitochondrial dysfunction can manifest as a wide range of health problems, such as neurodegenerative diseases, metabolic disorders, cardiovascular disease, immune dysfunction and cancer.1 There are many triggers of mitochondrial dysfunction, including obesity, chronic infections, heavy metal toxicity, micronutrient deficiencies, drug-induced nutrient deficiencies and direct drug-induced mitochondrial toxicity.2-7
By improving mitochondrial health, we can enhance cellular energy production, leading to better overall health. In this blog post, we will explore the three pillars of mitochondrial support: salugenesis, membrane lipid replacement, and micronutrient and antioxidant support.
The term salugenesis refers to the process and steps of health promotion that must be accomplished for healing from any injury or stress.8 The key elements of salugenesis include a balanced diet, regular exercise, toxin elimination, adequate sleep, social connections and connecting with nature. Because our daily choices significantly impact mitochondrial health, it is paramount to encourage patients to adopt a healthy lifestyle to maximize their cellular energy levels.
Diet especially plays a pivotal role in supporting salugenesis and healthy mitochondrial function. The Mediterranean diet in particular has been well studied for its promotion of health and longevity. Rich in polyphenols, fiber and polyunsaturated omega-3 fatty acids, the Mediterranean diet has been shown in several experimental models to increase mitochondrial metabolism, biogenesis and antioxidant capacity.9
Intermittent fasting or time-restricted eating may also enhance mitochondrial function. Studies suggest that fasting promotes cellular autophagy, which helps eliminate damaged mitochondria and promote healthy mitochondrial generation.
Furthermore, fasting has been shown to upregulate antioxidant gene expression of the genes TFAM, SOD2 and Nrf2.10 These antioxidant genes, particularly Nrf2, protect our cells and mitochondria from environmental stressors by supporting detoxification processes, reducing mitochondrial free radical damage and maximizing mitochondrial function.11
Membrane Lipid Replacement
The integrity of mitochondrial lipid membranes is vital for optimal energy production. As oxidative stress increases, membrane lipids are oxidized, becoming more rigid and fragmented, which allows ATP to leak out. Membrane lipid replacement (MLR) is a promising therapeutic strategy for restoring and maintaining healthy mitochondrial membrane fluidity and mitochondrial membrane potential for energy generation.
MLR uses high doses (2-10 grams per day) of food-derived phospholipids to remove damaged, oxidized membrane lipids in the mitochondria, improving mitochondrial function and reducing fatigue.12 Specifically, MLR has been shown to increase mitochondrial function and decrease fatigue in chronic fatigue syndrome, fibromyalgia and other fatiguing conditions.13
Micronutrient and Antioxidant Support
Micronutrients and antioxidants play a crucial role in supporting mitochondrial health. The following micronutrients have been well studied for their ability to support energy and combat fatigue:14
- B vitamins
- Vitamins C and D
- Coenzyme Q10 (CoQ10)
- Alpha lipoic acid (ALA)
- Acetyl L-carnitine (ALC)
- N-acetyl cysteine (NAC)
L-carnitine supplementation demonstrated significant improvements in physical fatigue, mental fatigue and fatigue severity.15 In fact, combining these micronutrient strategies can result in significant clinical synergy. A 2006 study by Kaiser et al of HIV-infected patients taking stable HAART found that the patients who took the combination of 1,000 mg ALC, 400 mg ALA and 1,200 mg NAC daily along with key micronutrients significantly increased their CD4 lymphocyte counts by 24% after 12 weeks.16
Patients should also be encouraged to consume antioxidants in their diet, but given changes in nutritional density from modern agricultural practices, supplementation with plant-derived antioxidants, such as sulforaphane from broccoli, EGCG from green tea and resveratrol from grapes, can give mitochondria a much-needed boost by reducing oxidative stress.17-19
Strategic Synergy for Mitochondrial Energy
Addressing lifestyle factors, particularly a nutrient-dense diet rich in polyphenols, as well as adequate sleep and movement, can all help to optimize mitochondrial function and recovery. By focusing on these three key categories—salugenesis, MLR, and micronutrient and antioxidant support—clinicians can help improve mitochondrial health and enhance cellular energy production. Educating patients about the importance of these interventions and encouraging healthy habits can improve health outcomes, vitality and overall well-being.
For more information on addressing mitochondrial dysfunction with lifestyle and nutrition, click here to download our new mitochondria white paper!
- For a useful clinical resource that educates patients on boosting their cellular energy, check out our Mitochondrial Health Presentation Pad, featuring lifestyle and nutraceutical support strategies.
- If you’re looking for a comprehensive clinical practice guide for supporting immune health and addressing numerous potential causes of fatigue, check out our Immune Foundations Program In-Practice Guide.
- Are you just getting started on or looking to level up your functional medicine practice? Our resources provide you with the confidence and knowledge you need to achieve success. The Immune Foundations Program includes essential clinical, patient education and marketing resources. Access all the program content and more with an LMRC membership.
Kareem Kandil, MD, ND is the Immune Foundations Clinical Brand Manager at Lifestyle Matrix Resource Center. Upon graduating from medical school at Ross University School of Medicine, Dr. Kandil went on to do an observership in integrative medicine and then pursued his Doctorate of Naturopathic Medicine (ND) at National University of Health Sciences in Lombard, IL.
- Nicolson GL. Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements. Integr Med (Encinitas). 2014 Aug;13(4):35-43.
- Kusminski CM, Scherer PE. Mitochondrial dysfunction in white adipose tissue. Trends Endocrinol Metab. 2012;23(9):435-443. doi:10.1016/j.tem.2012.06.004
- Jaishankar M, Tseten T, Anbalagan N, Mathew BB, Beeregowda KN. Toxicity, mechanism and health effects of some heavy metals. Interdiscip Toxicol. 2014;7(2):60-72. doi:10.2478/intox-2014-0009
- Peacock BN, Gherezghiher TB, Hilario JD, Kellermann GH. New insights into Lyme disease. Redox Biol. 2015;5:66-70. doi:10.1016/j.redox.2015.03.002
- Bailey RL, West KP Jr, Black RE. The epidemiology of global micronutrient deficiencies. Ann Nutr Metab. 2015;66 Suppl 2:22-33. doi:10.1159/000371618
- Yalcin N, Armut M, Kelleci Cakir B, Demirkan K. Drug-induced nutritional disorders. Clin Sci Nutr. 2020;1(3):113-122. https://doi.org/10.5152/clinscinutr.2020.962
- Brinkman K, Kakuda TN. Mitochondrial toxicity of nucleoside analogue reverse transcriptase inhibitors: a looming obstacle for long-term antiretroviral therapy?. Curr Opin Infect Dis. 2000;13(1):5-11. doi:10.1097/00001432-200002000-00002
- Naviaux RK. Mitochondrial and metabolic features of salugenesis and the healing cycle. Mitochondrion. 2023;70:131-163. https://doi.org/10.1016/j.mito.2023.04.003
- Khalil M, Shanmugam H, Abdallah H, et al. The Potential of the Mediterranean Diet to Improve Mitochondrial Function in Experimental Models of Obesity and Metabolic Syndrome. Nutrients. 2022;14(15):3112. Published 2022 Jul 28. doi:10.3390/nu14153112
- Madkour MI, T El-Serafi A, Jahrami HA, et al. Ramadan diurnal intermittent fasting modulates SOD2, TFAM, Nrf2, and sirtuins (SIRT1, SIRT3) gene expressions in subjects with overweight and obesity. Diabetes Res Clin Pract. 2019;155:107801. doi:10.1016/j.diabres.2019.107801
- Buendia I, Michalska P1, Navarro E, et al. Nrf2-ARE pathway: An emerging target against oxidative stress and neuroinflammation in neurodegenerative diseases. Pharmacol Ther. 2016 Jan;157:84-104.
- Nicolson GL, Settineri R. Lipid Replacement Therapy: a functional food approach with new formulations for reducing cellular oxidative damage, cancer-associated fatigue and the adverse effects of cancer therapy. Funct Foods Health Dis. 2011;1(4):135–160.
- Ellithorpe RR, Settineri RA, Nicolson GL. Pilot study: reduction of fatigue by use of a dietary supplement containing glycophospholipids. J Am Nutraceutical Assoc. 2003;6(1):23-28.
- Tardy AL, Pouteau E, Marquez D, Yilmaz C, Scholey A. Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence. Nutrients. 2020;12(1):228. Published 2020 Jan 16. doi:10.3390/nu12010228
- Malaguarnera M, Cammalleri L, Gargante MP, et al. L-carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr. 2007;86(6):1738–1744.
- Kaiser JD, Campa AM, Ondercin JP, Leoung GS, Pless RF, Baum MK. Micronutrient supplementation increases CD4 count in HIV-infected individuals on highly active antiretroviral therapy: a prospective, double-blinded, placebo-controlled trial. J Acquir Immune Defic Syndr. 2006;42(5):523-528. doi:10.1097/01.qai.0000230529.25083.42
- Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell. 2006; 127:1109–1122.
- Oliveira MR, Nabavi SF, Daglia M, Rastrelli L, Nabavi SM. Epigallocatechin gallate and mitochondria-A story of life and death. Pharmacol Res. 2016;104:70-85. doi:10.1016/j.phrs.2015.12.027
- Carrasco-Pozo C, Tan KN, Borges K. Sulforaphane is anticonvulsant and improves mitochondrial function. J Neurochem. 2015;135(5):932-942. doi:10.1111/jnc.133