Mitochondria are essential for metabolism. They are the cell’s powerhouse that turns glucose (or
fatty acids) into ATP (energy) so the cell can function. Studies have revealed a significant reduction (~40%) in mitochondrial density (less and smaller mitochondria) in the muscle cells of people with insulin resistance [1]. Insulin resistant individuals also have a reduction in the expression of mitochondrial genes and important molecules involved in metabolism [2].
When glucose and fatty acids are turned into ATP, a by-product of the reaction are free radicals.
When functioning normally, transient increases of free radicals are not harmful, as mitochondria have a process to regulate free radicals so they don’t cause damage to the mitochondria or the cell.
However, when there is too much glucose and fat, your mitochondria become stressed. Free radicals build up, triggering inflammatory pathways and damaging the mitochondria [3].
In an attempt to lower free radical formation, the mitochondria slows down your metabolism, becoming less efficient at burning fuel and making ATP (energy). The free radicals send out stress signals to block insulin receptors, thereby preventing more glucose from entering the cell. This contributes to insulin resistance. When glucose starts building up in the blood, it is sent to the liver to be turned into fat. This fat is then shuttled around the body, sometimes ending up in liver and muscle cells.
Fatty acid build up in the cell also alters insulin signalling pathways, leading to insulin resistance [4]. This occurs because the cell is trying to adapt to the excess energy it’s dealing with. Since it has so much fat to burn, it doesn’t need glucose, so it ignores insulin.
Insulin normally boosts mitochondrial function and increases their efficiency; but, when you become insulin resistant, the cells don’t get this signal, and mitochondrial function becomes further impaired.
It goes both ways—mitochondrial dysfunction contributes to insulin resistance and insulin resistance impairs mitochondrial function.
Mitochondrial dysfunction occurs when excess energy supply (calories consumed) is paired with low energy demand (physically inactive). So, paradoxically, when you have excess fuel to be burned for energy, you become less efficient at burning it in an effort to reduce free radicals. Even though the cell tries to adapt, the influx is too great, and you still see an increase in free radicals.
There is strong evidence that elevated fatty acids in the blood, muscle cells, and liver cells can cause mitochondrial dysfunction [4]. These fats come from dietary fat (predominantly saturated fat), excess carbohydrates that are converted to fat, and fat reservoirs on the body. As the cells become insulin resistant, glucose has a hard time getting into the cell; but, fat doesn’t need insulin to enter cells, so fatty acids continue to get in and clog up the cells.
Environmental toxins can also increase free radical production, causing damage to the mitochondria and to the cell. Persistent organic pollutants are fat-soluble toxins that accumulate and hide out in your cells for years, sometimes decades.
When mitochondrial dysfunction occurs in the pancreatic beta cells, they become less responsive to glucose. Rises of glucose in the blood would normally tell the pancreas to release insulin, so they secrete less insulin, which further fuels high blood sugars [5]. When the oxidative stress or glucose and fatty acid toxicity become too much, beta cells can self-destruct.
Mitochondrial dysfunction in the fat cells causes a release of inflammatory molecules, including one called resistin, which makes other cells in the body resistant to insulin [6]. Anti-inflammatory molecules are also suppressed, including an insulin-sensitising hormone called adiponectin.
How can you improve your mitochondrial function and capacity?
1. Physical activity
Physical activity increases the number and size of mitochondria. It also increases the number of insulin receptors and promotes insulin sensitivity.
Note: if you have mitochondrial dysfunction when you start exercising, you will be inefficient at burning glucose for energy. So, you may initially feel weak and unfit. But persist, because it will get easier as you slowly increase your capacity.
2. Metabolic flexibility
Improve metabolic flexibility, the ability of the cells to switch between fuel sources like fat and glucose. Avoid foods that are high in fat and carbohydrates, such as baked goods, breads, and unhealthy snacks (see my video and blog on metabolic flexibility.)
3. Intermittent fasting
Intermittent fasting helps to take the pressure off the mitochondria; it gives the body and cells a chance to self-regulate and clean up free radicals. It also allows the cells to burn excess fatty acids.
4. Fat loss
Weight loss often also results in loss of lean muscle, so it’s super important to be physically active in order to maintain lean muscle. Lean muscle promotes mitochondrial production and function.
5. Avoid processed foods
Avoid processed foods, particularly processed and refined carbohydrates. These are easy to over consume, and doing so leads to a surge in glucose and fat, which the mitochondria then struggle to process.
6. Minimise saturated fat
Minimise saturated fat, as saturated fats tend to clog up cells, putting extra strain on the mitochondria.
7. Antioxidants and phytonutrients
Consume a diet high in natural antioxidants and phytonutrients. Antioxidants and phytonutrients have been found to boost the regulation of mitochondrial function, increasing metabolic potential as well as sequestering (socking up) free radicals. Supplements and processed foods that claim to be high in antioxidants won’t cut it, you need to get these from real, whole foods like vegetables, fruit, legumes, wholegrains, nuts, and seeds.
8. Minimise toxins
Minimise your exposure to environmental toxins. A few simple ways to do this are to reduce your use of plastic, your intake of processed and take away foods, and your intake of animal products, as many of these toxins accumulate as you go up the food chain.
Mitochondria are essential to our metabolisms and our health. Prioritize these steps to improve your mitochondrial function and flexibility.
[1] Mitochondrial dysfunction in insulin insensitivity: implication of mitochondrial role in type 2
diabetes, Wang, Chih‐Hao ; Wang, Ching‐Chu ; Wei, Yau‐Huei, Annals of the New York Academy of Sciences, July 2010, Vol.12011(1), pp.157-165
[2] Mitochondrial Dysfunction, Insulin Resistance, and Potential Genetic Implications: Potential
Role of Alterations in Mitochondrial Function in the Pathogenesis of Insulin Resistance and Type 2 Diabetes, Panjamaporn Sangwung, Kitt Falk Petersen, Gerald I Shulman, Joshua W Knowles,
Endocrinology, April 2020, Volume 161, Issue 4,
[3] Mitochondrial dysfunction and insulin resistance: an update, Montgomery, Magdalene K ; Turner, Nigel, Endocrine connections, March 2015, Vol.4(1), pp.R1-R15
[4] Mitochondrial dysfunction in insulin resistance: differential contributions of chronic insulin and
saturated fatty acid exposure in muscle cells. Yang, Chenjing ; Aye, Cho Cho ; Li, Xiaoxin ; Diaz Ramos, Angels ; Zorzano, Antonio ; Mora, Silvia, Bioscience reports, October 2012, Vol.32(5), pp.465-478
[5] The pathogenetic role of β-cell mitochondria in type 2 diabetes. Fex, Malin ; Nicholas, Lisa M ; Vishnu, Neelanjan ; Medina, Anya ; Sharoyko, Vladimir V ; Nicholls, David G ; Spégel, Peter ; Mulder, Hindrik, The Journal of endocrinology, March 2018, Vol.236(3), pp.R145-R159
[6] Mitochondrial dysfunction in type 2 diabetes mellitus: an organ-based analysis Mark V. Pinti,
Garrett K. Fink, Quincy A. Hathaway, Andrya J. Durr, Amina Kunovac, and John M. Hollander, Division of Exercise Physiology American Journal Physiology Endocrinology Metabolism, 2019, 316:E268–E285
