Improve mitochondrial function
For optimal overall health and especially optimal mental health, we want to have large, strong mitochondria.
Dysfunctional mitochondria can contribute to a host of mental health issues such as depression, suicide, anxiety, insomnia, poor memory, poor attention and cognition, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
We get healthier mitochondria by:
- protecting mitochondria against excessive fission and stress
- maintaining an optimal balance between fission and fusion
- promoting appropriate mitophagy and mitochondrial biogenesis
- quenching ROS (reactive oxygen species) from dysfunctional mitochondria
We can support our mitochondria by following the guidelines below:
One of the keys to mitochondrial function is diet. As we have seen, overeating, eating too often, or eating the wrong things, especially high calorie low nutrient dense foods and refined carbohydrates has a very detrimental effect on our mitochondria. By improving our diets, we can very much improve the health of our mitochondria.
- olive oil polyphenols which support the mitochondrial electron transport chain, stimulate mitochondrial biogenesisKikusato, M., Muroi, H., Uwabe, Y., Furukawa, K., & Toyomizu, M. (2016). Oleuropein induces mitochondrial biogenesis and decreases reactive oxygen species generation in cultured avian muscle cells, possibly via an up-regulation of peroxisome proliferator-activated receptor γ coactivator-1α. Animal science journal = Nihon chikusan Gakkaiho, 87(11), 1371–1378. https://doi.org/10.1111/asj.12559, https://pubmed.ncbi.nlm.nih.gov/26916829/ [accessed 10th November 2020] Hao, J., Shen, W., Yu, G., Jia, H., Li, X., Feng, Z., Wang, Y., Weber, P., Wertz, K., Sharman, E., & Liu, J. (2010). Hydroxytyrosol promotes mitochondrial biogenesis and mitochondrial function in 3T3-L1 adipocytes. The Journal of nutritional biochemistry, 21(7), 634–644. https://doi.org/10.1016/j.jnutbio.2009.03.012, https://pubmed.ncbi.nlm.nih.gov/19576748/ [accessed 10th November 2020]
- olive oil polyphenols can also increase neurotrophins to protect against neurodegeneration and depressionHassen, I., Casabianca, H. and Hosni, K., 2014. Biological Activities Of The Natural Antioxidant Oleuropein: Exceeding The Expectation – A Mini-Review. [online] Science Direct. <https://www.sciencedirect.com/science/article/pii/S1756464614002850> [Accessed 10 November 2020]. Lee, B., Shim, I., Lee, H., & Hahm, D. H. (2018). Oleuropein reduces anxiety-like responses by activating of serotonergic and neuropeptide Y (NPY)-ergic systems in a rat model of post-traumatic stress disorder. Animal cells and systems, 22(2), 109–117. https://doi.org/10.1080/19768354.2018.1426699, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138302/ [accessed 10th November 2020]
- in addition to olive oil, the UNESCO definition of the Mediterranean diet includes communal preparation and consumption – using crockery and glasses produced locally
- social enrichment from a strong sense of community is another driver of brain-supportive neurotrophinsGriffiths, R., 2018. Mitochondria in Health and Disease: Personalized Nutrition for Healthcare Practitioners. Singing Dragon.
- ketones, derived from fats, are especially supportive to the mitochondrial electron transport chain, and mitochondrial biogenesis
- mitochondria do better with ketones than with glucose, providing a better fuel to produce ATP
- ketones trigger epigenetic changes that improve mitochondria number and functionHasan-Olive, M. M., Lauritzen, K. H., Ali, M., Rasmussen, L. J., Storm-Mathisen, J., & Bergersen, L. H. (2019). A Ketogenic Diet Improves Mitochondrial Biogenesis and Bioenergetics via the PGC1α-SIRT3-UCP2 Axis. Neurochemical research, 44(1), 22–37. https://doi.org/10.1007/s11064-018-2588-6, https://pubmed.ncbi.nlm.nih.gov/30027365/ [accessed 10th November 2020] Yang, H., Shan, W., Zhu, F., Wu, J., & Wang, Q. (2019). Ketone Bodies in Neurological Diseases: Focus on Neuroprotection and Underlying Mechanisms. Frontiers in neurology, 10, 585. https://doi.org/10.3389/fneur.2019.00585, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581710/ [accessed 10th November 2020] Ruan, H. B., & Crawford, P. A. (2018). Ketone bodies as epigenetic modifiers. Current opinion in clinical nutrition and metabolic care, 21(4), 260–266. https://doi.org/10.1097/MCO.0000000000000475, https://pubmed.ncbi.nlm.nih.gov/29697540/ [accessed 10th November 2020]
- however ketogenic diets don’t work for everyone, and for some, especially those with excessively damaged mitochondria, it can be too hard on the system
- rich in fruit and vegetables which contain many mitochondria supporting phytonutrients
- be careful to include sufficient vitamin B12 and choline
Certain nutrients are vital to protecting our mitochondria from inflammation, ROS and dysfunction.
Works as an essential cofactor within the Electron Transport Chain (ETC), which is vital for sufficient ATP and protects against ROS.Andalib, S., Mashhadi-Mousapour, M., Bijani, S., & Hosseini, M. J. (2019). Coenzyme Q10 Alleviated Behavioral Dysfunction and Bioenergetic Function in an Animal Model of Depression. Neurochemical research, 44(5), 1182–1191. https://doi.org/10.1007/s11064-019-02761-0, https://pubmed.ncbi.nlm.nih.gov/30820817/ [accessed 10 November 2020].
- in animal models, vitamin E supplementation has been found to reverse age-related declines in ATP and increases in mitochondrial ROS in the hippocampus and frontal cortex – both implicated in depression
- vitamin E was able to restore mitochondrial mass in the hippocampus and maintain synaptic mitochondrial biogenesisNavarro, A., Bandez, M. J., Lopez-Cepero, J. M., Gómez, C., & Boveris, A. (2011). High doses of vitamin E improve mitochondrial dysfunction in rat hippocampus and frontal cortex upon aging. American journal of physiology. Regulatory, integrative and comparative physiology, 300(4), R827–R834. https://doi.org/10.1152/ajpregu.00525.2010, https://pubmed.ncbi.nlm.nih.gov/21106913/ [ accessed 10 November 2020].
- acting via retinoic acid receptors, vitamin A can help support mitochondrial biogenesis and the utilisation of fat for energy (beta oxidation)Tripathy, S., Chapman, J. D., Han, C. Y., Hogarth, C. A., Arnold, S. L., Onken, J., Kent, T., Goodlett, D. R., & Isoherranen, N. (2016). All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver. Molecular pharmacology, 89(5), 560–574. https://doi.org/10.1124/mol.116.103697, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851298/ [accessed 10 November 2020].
- essential for thyroid hormone actionBrent G. A. (2012). Mechanisms of thyroid hormone action. The Journal of clinical investigation, 122(9), 3035–3043. https://doi.org/10.1172/JCI60047, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433956/ [accessed 10 November 2020]., which is also important for mitochondria
- important for nerve regeneration, particularly the outgrowth of axonsPuttagunta, R., & Di Giovanni, S. (2012). Retinoic acid signaling in axonal regeneration. Frontiers in molecular neuroscience, 4, 59. https://doi.org/10.3389/fnmol.2011.00059, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249608/ [accessed 10 November 2020].
- lessens microglial activation, thereby reducing inflammation in the brainRegen, F., Hellmann-Regen, J., Costantini, E., & Reale, M. (2017). Neuroinflammation and Alzheimer’s Disease: Implications for Microglial Activation. Current Alzheimer research, 14(11), 1140–1148. https://doi.org/10.2174/1567205014666170203141717, https://pubmed.ncbi.nlm.nih.gov/28164764/ [accessed 10 November 2020].
- can also enhance acetylcholine, the neurotransmitter essential to memory and cognitive functionSzutowicz, A., Bielarczyk, H., Jankowska-Kulawy, A., Ronowska, A., & Pawełczyk, T. (2015). Retinoic acid as a therapeutic option in Alzheimer’s disease: a focus on cholinergic restoration. Expert review of neurotherapeutics, 15(3), 239–249. https://doi.org/10.1586/14737175.2015.1008456, https://pubmed.ncbi.nlm.nih.gov/25683350/ [accessed 10 November 2020].
- mitochondria have nicotinic acetylcholine receptors – when activated these acetylcholine receptors inhibit mtDNA release from mitochondria and block inflammasome activationLu, B., Kwan, K., Levine, Y. A., Olofsson, P. S., Yang, H., Li, J., Joshi, S., Wang, H., Andersson, U., Chavan, S. S., & Tracey, K. J. (2014). α7 nicotinic acetylcholine receptor signaling inhibits inflammasome activation by preventing mitochondrial DNA release. Molecular medicine (Cambridge, Mass.), 20(1), 350–358. https://doi.org/10.2119/molmed.2013.00117, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153835/ [accessed 10 November 2020].
- folate deficiency has been linked with depressionDean, O. M., Turner, A., Malhi, G. S., Ng, C., Cotton, S. M., Dodd, S., Sarris, J., Samuni, Y., Tanious, M., Dowling, N., Waterdrinker, A., Smith, D., & Berk, M. (2015). Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), 37(1), 3–12. https://doi.org/10.1590/1516-4446-2013-1341, https://pubmed.ncbi.nlm.nih.gov/25295681/ [accessed 10 November 2020].
- folate metabolism within mitochondria supports mtDNA synthesis and consequently mitochondrial integrityYuwen Xiu, Martha S Field, The Roles of Mitochondrial Folate Metabolism in Supporting Mitochondrial DNA Synthesis, Oxidative Phosphorylation, and Cellular Function, Current Developments in Nutrition, Volume 4, Issue 10, October 2020, https://doi.org/10.1093/cdn/nzaa153, https://academic.oup.com/cdn/article/4/10/nzaa153/5911573 [accessed 10 November 2020].
- vitamins B1, B6 and biotin all play vital roles in maintaining ATP production within mitochondriaDepeint, F., Bruce, W. R., Shangari, N., Mehta, R., & O’Brien, P. J. (2006). Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. Chemico-biological interactions, 163(1-2), 94–112. https://doi.org/10.1016/j.cbi.2006.04.01, https://pubmed.ncbi.nlm.nih.gov/16765926/ [accessed 10 November 2020].
- choline is an important component of phospholipids which help to build cell membranes, synapses and the inner mitochondrial membraneCansev M. (2016). Synaptogenesis: Modulation by Availability of Membrane Phospholipid Precursors. Neuromolecular medicine, 18(3), 426–440. https://doi.org/10.1007/s12017-016-8414-x, https://pubmed.ncbi.nlm.nih.gov/27250850/ [accessed 10 November 2020]. Paradies, G., Paradies, V., De Benedictis, V., Ruggiero, F. M., & Petrosillo, G. (2014). Functional role of cardiolipin in mitochondrial bioenergetics. Biochimica et biophysica acta, 1837(4), 408–417. https://doi.org/10.1016/j.bbabio.2013.10.006, https://pubmed.ncbi.nlm.nih.gov/24183692/ [accessed 10 November 2020].
- a choline-deficient diet will compromise the synthesis of cardiolipin, the ‘glue’ that holds the mitochondrial electron transport chain togetherParadies, G., Paradies, V., De Benedictis, V., Ruggiero, F. M., & Petrosillo, G. (2014). Functional role of cardiolipin in mitochondrial bioenergetics. Biochimica et biophysica acta, 1837(4), 408–417. https://doi.org/10.1016/j.bbabio.2013.10.006, https://pubmed.ncbi.nlm.nih.gov/24183692/ [accessed 10 November 2020].
- choline is required for the neurotransmitter acetylcholine which acts via the vagus nerve to reduce inflammation and support mitochondriaLu, B., Kwan, K., Levine, Y. A., Olofsson, P. S., Yang, H., Li, J., Joshi, S., Wang, H., Andersson, U., Chavan, S. S., & Tracey, K. J. (2014). α7 nicotinic acetylcholine receptor signaling inhibits inflammasome activation by preventing mitochondrial DNA release. Molecular medicine (Cambridge, Mass.), 20(1), 350–358. https://doi.org/10.2119/molmed.2013.00117, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153835/ [accessed 10 November 2020].
- plays an important role in stabilising mtDNA gene transcriptionFakruddin, M., Wei, F. Y., Suzuki, T., Asano, K., Kaieda, T., Omori, A., Izumi, R., Fujimura, A., Kaitsuka, T., Miyata, K., Araki, K., Oike, Y., Scorrano, L., Suzuki, T., & Tomizawa, K. (2018). Defective Mitochondrial tRNA Taurine Modification Activates Global Proteostress and Leads to Mitochondrial Disease. Cell reports, 22(2), 482–496. https://doi.org/10.1016/j.celrep.2017.12.051, https://pubmed.ncbi.nlm.nih.gov/29320742/ [accessed 10 November 2020].
- is an effective mitochondrial antioxidantWollenman, L. C., Vander Ploeg, M. R., Miller, M. L., Zhang, Y., & Bazil, J. N. (2017). The effect of respiration buffer composition on mitochondrial metabolism and function. PloS one, 12(11), e0187523. https://doi.org/10.1371/journal.pone.0187523, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5665555/ [accessed 10 November 2020].
- a readily available source of mitochondrial energy that does not require active transport into mitochondria
- Medium-chain triglycerides (MCTs) can trigger diarrhoea in some individuals and have been linked to EFA deficiencies when supplemented long-termIngrid Tein, Chapter 40 – Lipid Storage Myopathies Due to Fatty Acid Oxidation Defects, Editor(s): Basil T. Darras, H. Royden Jones, Monique M. Ryan, Darryl C. De Vivo, Neuromuscular Disorders of Infancy, Childhood, and Adolescence (Second Edition), Academic Press, 2015, Pages 761-795, ISBN 9780124170445, https://doi.org/10.1016/B978-0-12-417044-5.00040-8, http://www.sciencedirect.com/science/article/pii/B9780124170445000408 [accessed 10 November 2020].
- MCTs used in support of a ketogenic diet help with neurotransmitter and mitochondrial function in the CNSGano, L. B., Patel, M., & Rho, J. M. (2014). Ketogenic diets, mitochondria, and neurological diseases. Journal of lipid research, 55(11), 2211–2228. https://doi.org/10.1194/jlr.R048975, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617125/ [accessed 10 November 2020].
- protect against insulin resistance and metabolic syndromeWang, Y., Liu, Z., Han, Y., Xu, J., Huang, W., & Li, Z. (2018). Medium Chain Triglycerides enhances exercise endurance through the increased mitochondrial biogenesis and metabolism. PloS one, 13(2), e0191182. https://doi.org/10.1371/journal.pone.0191182, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805166/ [accessed 10 November 2020].
- support mitochondrial biogenesisWang, Y., Liu, Z., Han, Y., Xu, J., Huang, W., & Li, Z. (2018). Medium Chain Triglycerides enhances exercise endurance through the increased mitochondrial biogenesis and metabolism. PloS one, 13(2), e0191182. https://doi.org/10.1371/journal.pone.0191182, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805166/ [accessed 10 November 2020].
- mitochondria have a high need for vitamin C to neutralise the reactive oxygen species (ROS) they produceFiorani, M., Guidarelli, A., & Cantoni, O. (2020). Mitochondrial reactive oxygen species: the effects of mitochondrial ascorbic acid vs untargeted and mitochondria-targeted antioxidants. International journal of radiation biology, 1–8. Advance online publication. https://doi.org/10.1080/09553002.2020.1721604, https://pubmed.ncbi.nlm.nih.gov/31976796/ [accessed 10 November 2020].
- mitochondria have their own C transportersMuñoz-Montesino, C., Roa, F. J., Peña, E., González, M., Sotomayor, K., Inostroza, E., Muñoz, C. A., González, I., Maldonado, M., Soliz, C., Reyes, A. M., Vera, J. C., & Rivas, C. I. (2014). Mitochondrial ascorbic acid transport is mediated by a low-affinity form of the sodium-coupled ascorbic acid transporter-2. Free radical biology & medicine, 70, 241–254. https://doi.org/10.1016/j.freeradbiomed.2014.02.021, https://pubmed.ncbi.nlm.nih.gov/24594434/ [accessed 10 November 2020].
- increases glutathione
- improves insulin sensitivity
- is an integral part of the Kreb’s cycle within mitochondria
- promotes mitochondrial biogenesis
- is neuroprotective
Pereira, C., Chavarria, V., Vian, J., Ashton, M. M., Berk, M., Marx, W., & Dean, O. M. (2018). Mitochondrial Agents for Bipolar Disorder. The international journal of neuropsychopharmacology, 21(6), 550–569. https://doi.org/10.1093/ijnp/pyy018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007750/ [accessed 10 November 2020].
- effective at protecting mitochondria from oxidative stressKim, S. H., & Kim, H. (2018). Inhibitory Effect of Astaxanthin on Oxidative Stress-Induced Mitochondrial Dysfunction-A Mini-Review. Nutrients, 10(9), 1137. https://doi.org/10.3390/nu10091137, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165470/ [accessed 10 November 2020].
- can help increase ATP in hippocampal cells and support mtDNA and biogenesisBagheri, H., Ghasemi, F., Barreto, G. E., Rafiee, R., Sathyapalan, T., & Sahebkar, A. (2020). Effects of curcumin on mitochondria in neurodegenerative diseases. BioFactors (Oxford, England), 46(1), 5–20. https://doi.org/10.1002/biof.1566, https://pubmed.ncbi.nlm.nih.gov/31580521/ [accessed 10 November 2020].
- can protect tau proteins and help maintain the integrity of the cytoskeleton and ensure mitochondrial ATP transport to neuronsShytle, R. D., Tan, J., Bickford, P. C., Rezai-Zadeh, K., Hou, L., Zeng, J., Sanberg, P. R., Sanberg, C. D., Alberte, R. S., Fink, R. C., & Roschek, B., Jr (2012). Optimized turmeric extract reduces β-Amyloid and phosphorylated Tau protein burden in Alzheimer’s transgenic mice. Current Alzheimer research, 9(4), 500–506. https://doi.org/10.2174/156720512800492459, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474959/ [accessed 10 November 2020].
- resveratrolJardim, F. R., de Rossi, F. T., Nascimento, M. X., da Silva Barros, R. G., Borges, P. A., Prescilio, I. C., & de Oliveira, M. R. (2018). Resveratrol and Brain Mitochondria: a Review. Molecular neurobiology, 55(3), 2085–2101. https://doi.org/10.1007/s12035-017-0448-z, https://pubmed.ncbi.nlm.nih.gov/28283884/ [accessed 10 November 2020]. (found in grapes, berries, nuts and cocoa) and equolYao, J., Zhao, L., Mao, Z., Chen, S., Wong, K. C., To, J., & Brinton, R. D. (2013). Potentiation of brain mitochondrial function by S-equol and R/S-equol estrogen receptor β-selective phytoSERM treatments. Brain research, 1514, 128–141. https://doi.org/10.1016/j.brainres.2013.02.021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672394/ [accessed 10 November 2020]. (a soy metabolite from gut fermentation) have been found to benefit mitochondrial health and function
- epigallocatechin-3-gallate, a polyphenol found in green tea, has been shown to dramatically improve mitochondrial function in a study researching neurodegenerationDragicevic, N., Smith, A., Lin, X., Yuan, F., Copes, N., Delic, V., Tan, J., Cao, C., Shytle, R. D., & Bradshaw, P. C. (2011). Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer’s amyloid-induced mitochondrial dysfunction. Journal of Alzheimer’s disease : JAD, 26(3), 507–521. https://doi.org/10.3233/JAD-2011-101629, https://pubmed.ncbi.nlm.nih.gov/21694462/ [accessed 10 November 2020].
- found in green leafy vegetables
- protects against neurodegeneration and inflammationJi, R., Meng, L., Li, Q., & Lu, Q. (2015). TAM receptor deficiency affects adult hippocampal neurogenesis. Metabolic brain disease, 30(3), 633–644. https://doi.org/10.1007/s11011-014-9636-y, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414696/ [accessed 10 November 2020].
- in combination with vitamin C, vitamin K can help bypass blocks in mitochondrial metabolismIvanova, D., Zhelev, Z., Getsov, P., Nikolova, B., Aoki, I., Higashi, T., & Bakalova, R. (2018). Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect. Redox biology, 16, 352–358. https://doi.org/10.1016/j.redox.2018.03.013, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953218/ [accessed 10 November 2020].
- helps to maintain the integrity of the myelin sheathGoudarzi, S., Rivera, A., Butt, A. M., & Hafizi, S. (2016). Gas6 Promotes Oligodendrogenesis and Myelination in the Adult Central Nervous System and After Lysolecithin-Induced Demyelination. ASN neuro, 8(5), 1759091416668430. https://doi.org/10.1177/1759091416668430, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027908/ [accessed 10 November 2020].
- acting through its receptor (VDR) vitamin D regulates mitochondrial oxidative phosphorylation and so protects against ROSRicca, C., Aillon, A., Bergandi, L., Alotto, D., Castagnoli, C., & Silvagno, F. (2018). Vitamin D Receptor Is Necessary for Mitochondrial Function and Cell Health. International journal of molecular sciences, 19(6), 1672. https://doi.org/10.3390/ijms19061672, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032156/ [accessed 10 November 2020].
- Deficiency increases the risk of depression in later lifeBriggs, R., McCarroll, K., O’Halloran, A., Healy, M., Kenny, R. A., & Laird, E. (2019). Vitamin D Deficiency Is Associated With an Increased Likelihood of Incident Depression in Community-Dwelling Older Adults. Journal of the American Medical Directors Association, 20(5), 517–523. https://doi.org/10.1016/j.jamda.2018.10.006, https://pubmed.ncbi.nlm.nih.gov/30470577/ [accessed 10 November 2020].
- protects mitochondria
- helps keep calcium in check
- helps to regulate glutamate receptors and excitotoxicity
Griffiths, R., 2018. Mitochondria in Health and Disease: Personalized Nutrition for Healthcare Practitioners. Singing Dragon.
- helps protect against excitotoxicity by regulating the glutamate receptorMlyniec K. (2015). Zinc in the Glutamatergic Theory of Depression. Current neuropharmacology, 13(4), 505–513. https://doi.org/10.2174/1570159×13666150115220617, https://pubmed.ncbi.nlm.nih.gov/26412070/ [accessed 10 November 2020].
- excitotoxicity happens when excess or unregulated glutamate allows calcium to flood the neurons, overwhelming the mitochondria, and leading to cell deathGriffiths, R., 2018. Mitochondria in Health and Disease: Personalized Nutrition for Healthcare Practitioners. Singing Dragon.
- both zinc and magnesium protect against excitotoxicity by decreasing glutamate dependent neurotransmissionMlyniec K. (2015). Zinc in the Glutamatergic Theory of Depression. Current neuropharmacology, 13(4), 505–513. https://doi.org/10.2174/1570159×13666150115220617, https://pubmed.ncbi.nlm.nih.gov/26412070/ [accessed 10 November 2020].
- patients with major depressive disorder have been shown to have low zinc and low magnesiumMlyniec K. (2015). Zinc in the Glutamatergic Theory of Depression. Current neuropharmacology, 13(4), 505–513. https://doi.org/10.2174/1570159×13666150115220617, https://pubmed.ncbi.nlm.nih.gov/26412070/ [accessed 10 November 2020].
Omega 3 fatty acids
- change the phospholipid profile of mitochondrial membranes
- DHA displaces the omega 6 fatty acid arachidonic acid in mitochondria, resulting in increased levels of the mitochondrial phospholipid cardiolipinStanley, W. C., Khairallah, R. J., & Dabkowski, E. R. (2012). Update on lipids and mitochondrial function: impact of dietary n-3 polyunsaturated fatty acids. Current opinion in clinical nutrition and metabolic care, 15(2), 122–126. https://doi.org/10.1097/MCO.0b013e32834fdaf7, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067133/ [accessed 10 November 2020].
- cardiolipin is the ‘glue’ that holds the electron transport chain together
- anthocyanin in berries is especially protective of neuronal mitochondriaUllah, R., Khan, M., Shah, S. A., Saeed, K., & Kim, M. O. (2019). Natural Antioxidant Anthocyanins-A Hidden Therapeutic Candidate in Metabolic Disorders with Major Focus in Neurodegeneration. Nutrients, 11(6), 1195. https://doi.org/10.3390/nu11061195, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628002/ [accessed 10 November 2020].
- aspalathin, a flavonoid found in rooibos tea, acts as a powerful mitochondrial antioxidantMattera, R., Benvenuto, M., Giganti, M. G., Tresoldi, I., Pluchinotta, F. R., Bergante, S., Tettamanti, G., Masuelli, L., Manzari, V., Modesti, A., & Bei, R. (2017). Effects of Polyphenols on Oxidative Stress-Mediated Injury in Cardiomyocytes. Nutrients, 9(5), 523. https://doi.org/10.3390/nu9050523, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452253/ [accessed 10 November 2020].
- stabilises the mitochondrial membrane potential – an indicator of mitochondrial healthTan, D. X., Manchester, L. C., Qin, L., & Reiter, R. J. (2016). Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics. International journal of molecular sciences, 17(12), 2124. https://doi.org/10.3390/ijms17122124, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187924/ [accessed 10 November 2020].
- melatonin is preferentially taken up by mitochondria – no other antioxidant does thisSrinivasan, V., Spence, D. W., Pandi-Perumal, S. R., Brown, G. M., & Cardinali, D. P. (2011). Melatonin in mitochondrial dysfunction and related disorders. International journal of Alzheimer’s disease, 2011, 326320. https://doi.org/10.4061/2011/326320, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100547/ [accessed 10 November 2020].
- disrupted by light, even normal electric light at night and lack of sunlight during the dayTouitou, Y., Reinberg, A., & Touitou, D. (2017). Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption. Life sciences, 173, 94–106. https://doi.org/10.1016/j.lfs.2017.02.008, https://pubmed.ncbi.nlm.nih.gov/28214594/ [accessed 10 November 2020].
There is a strong link between membrane strength and mitochondrial integrity. Damaged mitochondria and lead to damage gut and blood brain barriers, and damaged gut can compromise the mitochondria.
Soluble fibre and short-chain fatty acids
- fermentation of fibre in the gut produces short-chain fatty acids (SCFAs)
- SCFAs improve gut and blood brain barrier integrity by reducing permeability in bothSilva, Y. P., Bernardi, A., & Frozza, R. L. (2020). The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Frontiers in endocrinology, 11, 25. https://doi.org/10.3389/fendo.2020.00025, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005631/ [accessed 10th November 2020] Parada Venegas, D., De la Fuente, M. K., Landskron, G., González, M. J., Quera, R., Dijkstra, G., Harmsen, H., Faber, K. N., & Hermoso, M. A. (2019). Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Frontiers in immunology, 10, 277. https://doi.org/10.3389/fimmu.2019.00277, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421268/ [accessed 10th November 2020]
- SCFAs are thought to improve barrier integrity by powering mitochondria to keep barrier tight junctions intact
- SCFAs help to modulate the gut-brain axis, reducing brain inflammation and supporting neurotrophin activitySilva, Y. P., Bernardi, A., & Frozza, R. L. (2020). The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Frontiers in endocrinology, 11, 25. https://doi.org/10.3389/fendo.2020.00025, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005631/ [accessed 10th November 2020] Parada Venegas, D., De la Fuente, M. K., Landskron, G., González, M. J., Quera, R., Dijkstra, G., Harmsen, H., Faber, K. N., & Hermoso, M. A. (2019). Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Frontiers in immunology, 10, 277. https://doi.org/10.3389/fimmu.2019.00277, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421268/ [accessed 10th November 2020]
- the SCFA butyrate supports mitochondria by reducing ROS productionClark, A., & Mach, N. (2017). The Crosstalk between the Gut Microbiota and Mitochondria during Exercise. Frontiers in physiology, 8, 319. https://doi.org/10.3389/fphys.2017.00319, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437217/ [accessed 10th November 2020]
- many lactobacillus and bifidobacterium species support the gut-brain axis by curbing inflammation and cortisol levels, which can result in a reduction of symptoms of depression and anxiety.Misra, S., & Mohanty, D. (2019). Psychobiotics: A new approach for treating mental illness?. Critical reviews in food science and nutrition, 59(8), 1230–1236. https://doi.org/10.1080/10408398.2017.1399860, https://pubmed.ncbi.nlm.nih.gov/29190117/ [accessed 10th November 2020]
As we have seen in the section on mitochondrial dysfunction, toxins can be highly damaging to our mitochondria.
Drink ample water and fibre to support elimination of waste through the kidneys and bowels.
- sleep and exercise will upregulate the glymphatic system to clear metabolic waste from the Central Nervous System (CNS)
- in excess, the excitatory neurotransmitter glutamate is associated with mitochondrial dysfunction and excitotoxicity
- glutamate is detoxified via the Kreb’s cycle and doubles up as a mitochondrial fuelFendt, S. M., & Verstreken, P. (2017). Neurons eat glutamate to stay alive. The Journal of cell biology, 216(4), 863–865. https://doi.org/10.1083/jcb.201702003, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379959/ [accessed 10th November 2020]
- detoxification of the neurotransmitter dopamine accelerates as we age and can dangerously increase a dopamine metabolite called DOPAL
- DOPAL is 1000 times more toxic than dopamine and is a potent mitochondrial toxinGriffiths, R., 2019. Parkinson’s Disease – An In-Depth Metabolic Guide. Amazon Digital Services Kristal, B. S., Conway, A. D., Brown, A. M., Jain, J. C., Ulluci, P. A., Li, S. W., & Burke, W. J. (2001). Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria. Free radical biology & medicine, 30(8), 924–931. https://doi.org/10.1016/s0891-5849(01)00484-1, https://pubmed.ncbi.nlm.nih.gov/11295535/ [accessed 10th November 2020]
- curcumin, luteolin, quercetin, ursolic acid, rutin, catechin and berry anthocyanins and DHA are natural compounds which all have some degree of MAO-inhibitory activity
- slowing down MAO and dopamine detoxification will reduce harmful levels of DOPALGriffiths, R., 2019. Parkinson’s Disease – An In-Depth Metabolic Guide. Amazon Digital Services
- oxidative stress also damages lipid membranes in a process called lipid peroxidation
- lipid peroxides are associated with an increased risk of depressionMazereeuw, G., Herrmann, N., Andreazza, A. C., Scola, G., Ma, D., Oh, P. I., & Lanctôt, K. L. (2017). Oxidative stress predicts depressive symptom changes with omega-3 fatty acid treatment in coronary artery disease patients. Brain, behavior, and immunity, 60, 136–141. https://doi.org/10.1016/j.bbi.2016.10.005, https://pubmed.ncbi.nlm.nih.gov/27742581/ [accessed 10th November 2020]
- lipid peroxides can be detoxified by mitochondria but mitochondria can become easily damaged by them as levels increase
- high alcohol intake can compromise lipid peroxide detoxificationZhong, H., & Yin, H. (2015). Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: focusing on mitochondria. Redox biology, 4, 193–199. https://doi.org/10.1016/j.redox.2014.12.011, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803793/ [accessed 10th November 2020]
As seen in mitochondria dysfunction, hormesis is a strategy where the body employs a small amount of stress to induce positive compensatory reactions, which then heal and strengthen us.
Within limits, we evolve when pushed and challenged – and grow stronger because of these beneficial challenges. However, if we go beyond our limits, this is when dysfunction ensues.
Hormesis, and more specifically, mitohormesis (mitochondrial hormesis) promote mitophagy (the digestion of damaged mitochondria) and mitochondrial biogenesis.Ristow, M., & Schmeisser, K. (2014). Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS). Dose-response : a publication of International Hormesis Society, 12(2), 288–341. https://doi.org/10.2203/dose-response.13-035.Ristow, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036400/ [accessed 10th November 2020]
Mitohormesis conditions our mitochondria to handle stressZimmermann, A., Bauer, M. A., Kroemer, G., Madeo, F., & Carmona-Gutierrez, D. (2014). When less is more: hormesis against stress and disease. Microbial cell (Graz, Austria), 1(5), 150–153. https://doi.org/10.15698/mic2014.05.148, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354599/ [accessed 10th November 2020], while staying in peace time metabolism rather than going into defense mode.
Ways to promote mitohormesis:
Fasting and exercise
- over 65s who regularly train and exercise have similar mitochondrial capacity as much younger peopleCoggan, A. R., Spina, R. J., King, D. S., Rogers, M. A., Brown, M., Nemeth, P. M., & Holloszy, J. O. (1992). Skeletal muscle adaptations to endurance training in 60- to 70-yr-old men and women. Journal of applied physiology (Bethesda, Md. : 1985), 72(5), 1780–1786. https://doi.org/10.1152/jappl.19220.127.116.110, https://pubmed.ncbi.nlm.nih.gov/1601786/ [accessed 10th November 2020]
- exercise increases ROS and the expression of SIRT anti-ageing proteins, which are essential for mitochondrial biogenesis, especially in the hippocampusCalabrese, V., Cornelius, C., Dinkova-Kostova, A. T., Calabrese, E. J., & Mattson, M. P. (2010). Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxidants & redox signaling, 13(11), 1763–1811. https://doi.org/10.1089/ars.2009.3074, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2966482/ [accessed 10th November 2020]
- chronic stress suppresses the expression of SIRT anti-ageing proteins, and can lead to hippocampal atrophy, which is a hallmark of depression and neurodegenerative diseases such as Alzheimer’sSapolsky R. M. (2001). Depression, antidepressants, and the shrinking hippocampus. Proceedings of the National Academy of Sciences of the United States of America, 98(22), 12320–12322. https://doi.org/10.1073/pnas.231475998, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/ [accessed 10th November 2020] Lu, G., Li, J., Zhang, H., Zhao, X., Yan, L. J., & Yang, X. (2018). Role and Possible Mechanisms of Sirt1 in Depression. Oxidative medicine and cellular longevity, 2018, 8596903. https://doi.org/10.1155/2018/8596903, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831942/ [accessed 10th November 2020] Halliday G. (2017). Pathology and hippocampal atrophy in Alzheimer’s disease. The Lancet. Neurology, 16(11), 862–864. https://doi.org/10.1016/S1474-4422(17)30343-5, https://pubmed.ncbi.nlm.nih.gov/29029840/ [accessed 10th November 2020]
Fruit and vegetables with high polyphenol content
- plant compounds, such as polyphenols, are mildly toxic, triggering hormesis, which then triggers our own antioxidants
- these antioxidants then in turn support mitochondriaFranco, R., Navarro, G., & Martínez-Pinilla, E. (2019). Hormetic and Mitochondria-Related Mechanisms of Antioxidant Action of Phytochemicals. Antioxidants (Basel, Switzerland), 8(9), 373. https://doi.org/10.3390/antiox8090373, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769633/ [accessed 10th November 2020]
- found in sea air, air ear waterfalls, after a rain
- trigger mitohormesis when breathing themM. N. Kondrashove et al., “The primary physico-chemical mechanism for the beneficial biological/medical effects of negative air ions,” in IEEE Transactions on Plasma Science, vol. 28, no. 1, pp. 230-237, Feb. 2000, doi: 10.1109/27.842910. https://ieeexplore.ieee.org/abstract/document/842910 [accessed 10th November 2020]
- hypoxia due to breath-holding practices strengthen mitochondria in the lungs through mitohormesis which upregulates endogenous antioxidantsCalabrese, V., Cornelius, C., Dinkova-Kostova, A. T., Calabrese, E. J., & Mattson, M. P. (2010). Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxidants & redox signaling, 13(11), 1763–1811. https://doi.org/10.1089/ars.2009.3074, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2966482/ [accessed 10th November 2020] Damiani, E., Brugè, F., Cirilli, I., Marcheggiani, F., Olivieri, F., Armeni, T., Cianfruglia, L., Giuliani, A., Orlando, P., & Tiano, L. (2018). Modulation of Oxidative Status by Normoxia and Hypoxia on Cultures of Human Dermal Fibroblasts: How Does It Affect Cell Aging?. Oxidative medicine and cellular longevity, 2018, 5469159. https://doi.org/10.1155/2018/5469159, https://pubmed.ncbi.nlm.nih.gov/30405877/ [accessed 10th November 2020]
Heat and cold
- extreme heat and extreme cold (eg: saunas and/or ice therapy)Rattan S. I. (2006). Hormetic modulation of aging and longevity by mild heat stress. Dose-response : a publication of International Hormesis Society, 3(4), 533–546. https://doi.org/10.2203/dose-response.003.04.008, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2477195/ [accessed 10th November 2020] Ristow, M., & Schmeisser, K. (2014). Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS). Dose-response : a publication of International Hormesis Society, 12(2), 288–341. https://doi.org/10.2203/dose-response.13-035.Ristow, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036400/ [accessed 10th November 2020]
Red and near infrared light and uv light
- red light interacts with mitochondria and boosts antioxidant levelsde Freitas, L. F., & Hamblin, M. R. (2016). Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy. IEEE journal of selected topics in quantum electronics : a publication of the IEEE Lasers and Electro-optics Society, 22(3), 7000417. https://doi.org/10.1109/JSTQE.2016.2561201, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215870/ [accessed 10th November 2020] Berry, R., 3rd, & López-Martínez, G. (2020). A dose of experimental hormesis: When mild stress protects and improves animal performance. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 242, 110658. https://doi.org/10.1016/j.cbpa.2020.110658, https://pubmed.ncbi.nlm.nih.gov/31954863/ [accessed 10th November 2020]
Romantic love and connection increase NGF (nerve growth factor) which enables mitochondria to repair neurons damaged by chronic stress.Emanuele E. (2011). NGF and romantic love. Archives italiennes de biologie, 149(2), 265–268. https://doi.org/10.4449/aib.v149i2.1367, https://pubmed.ncbi.nlm.nih.gov/21701998/ [accessed 10th November 2020]