Happy Mitochondria, Happy Body, Happy Life

With modern diets, our microbiomes & mitochondria are a bit hangry, and so is our health. Science and wisdom tradition shed light on making them happy again to reclaim health.

Hold the Simple Carbs, I’m Starving!

In the wise words of Justin and Erica Sonnenburg, “We are starving our microbial selves.”[1]  This is certainly true for our gut microbiome. Due to modern processing and food preference, our diets are significantly depleted of the prebiotic fibers, phytonutrients, good fats, and fermented foods that feed gut microbes.  

What is less known is this may also be true for key factors that regulate their microbial brethren – the mitochondria – believed to be long ago co-opted bacteria that live within each and every one of our cells. The so-called ‘endosymbiosis theory’ for the bacterial origin of mitochondria is an evolutionary story of epic proportions that might trump even that of the microbiome.  But that’s a story for another time.[2] 

Powerhouses & Gate Keepers of Health

For now, consider the mitochondria as our cell powerhouses. They take the nutrients we consume – protein, fat, carbohydrates, vitamins, and minerals – and convert them to the energy currency of the cell, ATP.  It’s much like how a hydroelectric dam converts water to electricity.[3] 

Nutrient signals produced by our microbiome from a healthy diet – B vitamins, modified polyphenols, butyrate, and other short and medium chain fatty acids – play an important role in telling the mitochondria when to grow and how to most efficiently adapt to the always changing food stream in our gut.[4–8] In modern diets consisting largely of ultra-processed foods, many of these factors are missing and our microbiome and mitochondria are confused and unhappy. 

When our microbiomes and mitochondria are not happy, we’re not happy, and our physical and mental health most certainly suffers. Indeed, noncommunicable diseases as diverse as obesity, diabetes, autoimmune disease, cancer, depression, and even Alzheimer’s have all been linked to both microbiome and mitochondrial dysfunction.[9–12]

Weight Loss Solutions Abound, Yet We Still Get More Round

When it comes to obesity and metabolic diseases, most of us probably don’t think about our mitochondria though. Instead we tend to think in terms of “calories in” and “calories out” – the so called energy balance model of obesity.[13]

Decreasing total calories ingested (e.g intermittent fasting), decreasing the proportion of calories that come from carbohydrates (e.g. ketogenic diets) and changing dietary composition to impact appetite (e.g. high protein and fiber) can all contribute to weight loss.(See Blog on Weight Loss, Part 1 and Part 2)

Increasing the calories burned – as in physical activity and exercise – is also quite effective at weight loss. Walks immediately after meals in particular, and activities of any type including choosing stairs over escalators and finding one’s preferred exercise can be truly impactful.[14] 

At the Crux of the Matter

All of these approaches work through the mitochondria, by alleviating the glut of energy (sugar and starch in particular) that puts oxidative stress on these important organelles.[15,16] It may be less appreciated that tweaking the energy equation at its fulcrum, the mitochondrial powerhouses themselves, is complementary to these approaches.[17] 

Habitual exercise increases mitochondria in muscle cells leading to more energy consumption even at rest.[18] Habitual cold therapy – think cold showers and icy dips – increases mitochondria in cell types like brown fat and muscle for the purpose of generating more heat.[19]

Many pharmaceutical approaches for blood sugar and weight loss impact mitochondria. For example both metformin and GLP-1 increase mitochondrial genesis.[20,21]  

Powerful Plants for our Mitochondrial Power Plants

Plant nutrients like fibers, polyphenols, fatty acids, and their fermented products can also signal to the mitochondria (via epigenetic regulation) to ramp up their efforts to process carbohydrates, especially after being processed by the microbiome.[4,22] 

In whole foods, carbohydrates naturally come packaged part and parcel with these molecules–think fiber and fatty acids in whole grains and polyphenols in grapes. In ultra-processed foods, they have largely been removed. We effectively consume all the carbohydrate energy without the natural signals that allow the mitochondria to adapt to a carbohydrate energy surplus.[23] 

When they don’t receive these signals it impacts processing of the energy.[24] Over time it contributes to metabolic gridlock (aka inflexibility) with fat accumulating inside the cells (obesity) and sugar in the blood (diabetes).[17] Even though there is plenty of energy, we do not efficiently process it.[23] 

There’s Wisdom in Tradition

So how might we jumpstart our microbiomes and mitochondria? Fibers, polyphenols, healthy fats, and their ferments work both independently and through microbiome conversion – modified polyphenols, conjugated fatty acids, MCTs, butyrate, and other SCFAs – to alert our mitochondrial powerhouses to the presence of carbohydrate nutrients, stimulating them to multiply and increase their activity.[25,26] (See Blog on the Four F’s)   

It is no coincidence that the Mediterranean diet, one of the most studied and healthiest diets from around the globe, contains these dietary components in spades. This is true also for other healthy diets around the globe like those profiled in Blue Zones – Icaria, Sardinia, Okinawa, Nicoya, and Loma Linda – parts of the world where people disproportionately live to 100+ years of age.[27]

So bon appétit to your microbiome & mitochondria! Here’s a short list of The Four Phonetic F’s of Food to help serve as a simple to follow guide.  And here’s a link to a gut health nutrition calculator to help you choose the most gut friendly foods!

The Four Phonetic F’s of Food

FIBERS (e.g. resistant starch, beta-glucan, arabinoxylan, inulin, pectin, gums)

-oats, barley & other whole grains

-beans, lentils & other legumes

-yams, potatoes & other tubers

-dark chocolate >70%

PHENOLS (e.g. curcumin, resveratrol, quercetin, EGCG, berberine)

-green tea, other teas & coffee

-berries, fruit & veggies

-turmeric, other spices & herbs

-dark chocolate >70%

HEALTHY FATS (e.g. omega-3 fatty acids)

-sardines, salmon & other fatty fish

-avocado, olives & their oils

-nuts, seeds & their butters

-dark chocolate >70%

FERMENTS (e.g. lactate, acetate, butyrate, conjugated fatty acids, probiotics)

-olives, pickles, sauerkraut, kimchi & miso

-vinegars, shrubs & kombucha

-yogurt, kefir, artisanal cheese

-dark chocolate >70%

More Articles & Resources

If you enjoyed this article, please feel free to visit gutbites.org where you’ll find more practical food and microbiome digests to improve gut health and lift your whole self! Also take a spin on the Gut Health Nutrition Calculator to help in gut healthy food choice!

MD-authored food & microbiome digests to demystify gut health.

1. Sonnenburg ED, Sonnenburg JL. Starving our Microbial Self: The Deleterious Consequences of a Diet Deficient in Microbiota-Accessible Carbohydrates. Cell Metab. 2014;20: 779. doi:10.1016/j.cmet.2014.07.003

2. Zachar I, Boza G. Endosymbiosis before eukaryotes: mitochondrial establishment in protoeukaryotes. Cell Mol Life Sci. 2020;77: 3503–3523. doi:10.1007/s00018-020-03462-6

3. Giacomello M, Pyakurel A, Glytsou C, Scorrano L. The cell biology of mitochondrial membrane dynamics. Nat Rev Mol Cell Biol. 2020;21: 204–224. doi:10.1038/s41580-020-0210-7

4. Amorim JA, Coppotelli G, Rolo AP, Palmeira CM, Ross JM, Sinclair DA. Mitochondrial and metabolic dysfunction in ageing and age-related diseases. Nat Rev Endocrinol. 2022;18. doi:10.1038/s41574-021-00626-7

5. Steliou K, Boosalis MS, Perrine SP, Sangerman J, Faller DV. Butyrate Histone Deacetylase Inhibitors. Biores Open Access. 2012;1: 192. doi:10.1089/biores.2012.0223

6. Shao L-W, Peng Q, Dong M, Gao K, Li Y, Li Y, et al. Histone deacetylase HDA-1 modulates mitochondrial stress response and longevity. Nat Commun. 2020;11: 1–12. doi:10.1038/s41467-020-18501-w

7. Vaughan RA, Garcia-Smith R, Bisoffi M, Conn CA, Trujillo KA. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells. Lipids Health Dis. 2012;11. doi:10.1186/1476-511X-11-142

8. Corrêa TAF, Rogero MM, Hassimotto NMA, Lajolo FM. The Two-Way Polyphenols-Microbiota Interactions and Their Effects on Obesity and Related Metabolic Diseases. Front Nutr. 2019;0. doi:10.3389/fnut.2019.00188

9. Diaz-Vegas A, Sanchez-Aguilera P, Krycer JR, Morales PE, Monsalves-Alvarez M, Cifuentes M, et al. Is Mitochondrial Dysfunction a Common Root of Noncommunicable Chronic Diseases? Endocr Rev. 2020;41: bnaa005. doi:10.1210/endrev/bnaa005

10. Rai P, Janardhan KS, Meacham J, Madenspacher JH, Lin WC, Karmaus PWF, et al. IRGM1 links mitochondrial quality control to autoimmunity. Nat Immunol. 2021;22. doi:10.1038/s41590-020-00859-0

11. Wallace DC. Mitochondria and cancer. Nat Rev Cancer. 2012;12: 685–698. doi:10.1038/nrc3365

12. Wang W, Zhao F, Ma X, Perry G, Zhu X. Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances. Mol Neurodegener. 2020;15: 1–22. doi:10.1186/s13024-020-00376-6

13. Hall KD, Farooqi IS, Friedman JM, Klein S, Loos RJF, Mangelsdorf DJ, et al. The energy balance model of obesity: beyond calories in, calories out. Am J Clin Nutr. 2022;115: 1243–1254. doi:10.1093/ajcn/nqac031

14. Hijikata Y, Yamada S. Walking just after a meal seems to be more effective for weight loss than waiting for one hour to walk after a meal. Int J Gen Med. 2011;4: 447. doi:10.2147/IJGM.S18837

15. The ketogenic diet as a therapeutic intervention strategy in mitochondrial disease. Int J Biochem Cell Biol. 2021;138: 106050. doi:10.1016/j.biocel.2021.106050

16. de Cabo R, Mattson MP. Effects of Intermittent Fasting on Health, Aging, and Disease. N Engl J Med. 2019 [cited 9 Sep 2022]. doi:10.1056/NEJMra1905136

17. Muoio DM. Metabolic Inflexibility: When Mitochondrial Indecision Leads to Metabolic Gridlock. Cell. 2014;159: 1253. doi:10.1016/j.cell.2014.11.034

18. Sorriento D, Di Vaia E, Iaccarino G. Physical Exercise: A Novel Tool to Protect Mitochondrial Health. Front Physiol. 2021;0. doi:10.3389/fphys.2021.660068

19. Kulterer OC, Niederstaetter L, Herz CT, Haug AR, Bileck A, Pils D, et al. The Presence of Active Brown Adipose Tissue Determines Cold-Induced Energy Expenditure and Oxylipin Profiles in Humans. J Clin Endocrinol Metab. 2020;105: 2203–2216. doi:10.1210/clinem/dgaa183

20. Kang MY, Oh TJ, Cho YM. Glucagon-Like Peptide-1 Increases Mitochondrial Biogenesis and Function in INS-1 Rat Insulinoma Cells. Endocrinol Metab Clin North Am. 2015;30: 216. doi:10.3803/EnM.2015.30.2.216

21. Metformin enhances mitochondrial biogenesis and thermogenesis in brown adipocytes of mice. Biomed Pharmacother. 2019;111: 1156–1165. doi:10.1016/j.biopha.2019.01.021

22. Chriett S, Dąbek A, Wojtala M, Vidal H, Balcerczyk A, Pirola L. Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. Sci Rep. 2019;9: 1–14. doi:10.1038/s41598-018-36941-9

23. Schneeberger M, Dietrich MO, Sebastián D, Imbernón M, Castaño C, Garcia A, et al. Mitofusin 2 in POMC Neurons Connects ER Stress with Leptin Resistance and Energy Imbalance. Cell. 2013;155: 172–187. doi:10.1016/j.cell.2013.09.003

24. Smith RL, Soeters MR, Wüst RCI, Houtkooper RH. Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease. Endocr Rev. 2018;39: 489. doi:10.1210/er.2017-00211

25. Han B, Lin CJ, Hu G, Wang MC. “Inside Out”- a dialogue between mitochondria and bacteria. FEBS J. 2019;286. doi:10.1111/febs.14692

26. Serrano JCE, Cassanye A, Martín-Gari M, Granado-Serrano AB, Portero-Otín M. Effect of Dietary Bioactive Compounds on Mitochondrial and Metabolic Flexibility. Diseases. 2016;4: 14. doi:10.3390/diseases4010014

27. Buettner D, Skemp S. Blue Zones: Lessons From the World’s Longest Lived. Am J Lifestyle Med. 2016;10. doi:10.1177/1559827616637066

2 responses to “Happy Mitochondria, Happy Body, Happy Life”

  1. You should look at Satvic Ayurvedic food and South Indian Brahmin Food both from India which is prevalent for centuries. They are very scientific ingredients and process of cooking. They are vegetarian though.

    1. Thanks for the great suggestion. There’s a lot of wisdom in tradition. I wonder the degree to which fermentation plays a role?

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