Fasting and Mitochondrial Health

Fasting has been used in therapeutic, cultural, and religious practices and traditions for thousands of years and is described as abstinence from some or all foods and drinks for a set period of time, usually longer than 12 hours. When fasting, the body experiences ketosis and undergoes a metabolic switch in its fuel source, from stored glycogen to fatty acids.¹ Several forms of intermittent fasting include the following:

• Alternate-day fasting: a cycle of fasting on one day and eating on the next day
• Time-restricted fastingcalories from food and beverages only during a hortened window of time daily, also called “prolonged nightly fasting,” which extends a person’s nightly fast to 12 hours or more
• 5:2 diet: five days of unrestricted eating, two non-consecutive days with one meal at 500–700 calories²
• Fasting mimicking diet: a plant-based diet program low in calories, sugars, and protein but high in unsaturated fats with the inclusion of supplements for vitamins, minerals, and essential fatty acids^3,4

Suggested benefits of fasting include improvements in mental or cognitive performance, cardiovascular health, type 2 diabetes, and obesity,^5-7 and fasting has been incorporated into various therapeutic nutritional strategies. For example, IFM’s Mitochondrial Food Plan is an anti-inflammatory, low-glycemic, gluten-free, low-grain, high-quality fat approach to eating that supports healthy mitochondria for improved energy production and that can be expanded with various levels of fasting. In the following video, IFM educator Monique Class, MS, APRN, BC, IFMCP, discusses the benefits of incorporating fasting with IFM’s Mitochondrial Food Plan.

Mitochondrial health

While long-term effects of intermittent fasting have not been fully established,⁸ studies suggest that some fasting benefits may be linked to optimizing mitochondrial function, leading to improved energy production and overall health.^9-11 Some of the potential benefits of intermittent fasting have primarily been established through animal research, observational studies, and anecdotal evidence. Additionally, fasting is not optimal for all patients, such as those who are pregnant, who have eating disorders, or who have type 1 diabetes.^8,12-15

Fission and fusion

Mitochondria have a range of functions, from generation of reactive oxygen species (ROS) to ATP synthesis, and mitochondrial health may impact the health of the body as a whole.⁹ Mitochondria are dynamic organelles undergoing continuous cycles of fusion and fission. While excessive division or fission has been associated with mitochondrial functional defects that may lead to multiple disease states,¹⁶ a recent study in nematode worms suggested that fasting may increase overall lifespan by promoting a balance between the fusion and fission states and homeostasis in mitochondrial networks.¹⁷

Mechanisms

Mitochondrial biogenesis and function are mediated by different activators, regulators, and transcription factors such as PGC-1α and Nrf2. Research has suggested that fasting may enhance these mediators to promote mitochondrial biogenesis and improve mitochondrial function. For example:

• The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a fasting-induced transcriptional co-activator¹⁸ that mediates mitochondrial biogenesis, activates when the body receives a signal that it needs more cellular energy, and increases in expression during fasting.¹
• Nuclear factor (erythroid-derived 2) factor 2 (Nrf2) is a transcription factor that regulates ROS production by mitochondria.²⁰ Studies suggest that Nrf2 is associated with mitochondrial biogenesis and may be involved in mitochondrial quality control systems.²¹ A 2019 study evaluated the impact of Ramadan intermittent fasting on the expression of antioxidant genes, including Nrf2, and results suggested that fasting improved the expression of the antioxidant regulatory genes.¹¹

Nutrition interventions

Specific nutrients that support mitochondrial function may be part of a personalized nutrition strategy for some patients. In other cases, a form of intermittent fasting may be appropriate, blended with a food plan to create an individualized nutrition intervention. Patients with a chronic disease may already have elevated levels of inflammation and oxidative stress, and their current diet may need to be stabilized to reduce overall inflammation before introducing fasting.

Functional Medicine provides a framework within which practitioners collaborate with patients to understand current conditions and develop personalized therapeutic strategies that potentially include nutrition interventions. IFM offers modifiable food plans, such as the Mitochondrial Food Plan, which supports optimal mitochondrial function, has great range and flexibility for implementation, and may incorporate different levels of fasting. Gain additional evaluation insights and tools on fasting and optimal mitochondrial function at the Energy Advanced Practice Module.

REFERENCES

1. Anton SD, Moehl K, Donahoo WT, et al. Flipping the metabolic switch: understanding and applying health benefits of fasting. Obesity (Silver Spring). 2018;26(2):254-268. doi:10.1002/oby.22065.
2. Conley M, Le Fevre L, Haywood C, Proietto J. Is two days of intermittent energy restriction per week a feasible weight loss approach in obese males? A randomized pilot study. Nutri Diet. 2018;75(1):65-72. doi:10.1111/1747-0080.12372.
3. Wei M, Brandhorst S, Shelehchi M, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017;9(377):pii:eaai8700. doi:10.1126/scitranslmed.aai8700.
4. Brandhorst S, Choi IY, Wei M, et al. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metab. 2015;22(1):86-99. doi:10.1016/j.cmet.2015.05.012.
5. Carter S, Clifton PM, Keogh JB. Effect of intermittent compared with continuous energy restricted diet on glycemic control in patients with type 2 diabetes: a randomized noninferiority trial. JAMA Netw Open. 2018;1(3):e180756. doi:10.1001/jamanetworkopen.2018.0756.
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10. Lettieri-Barbato D, Cannata SM, Casagrande V, Ciriolo MR, Aquilano K. Time-controlled fasting prevents aging-like mitochondrial changes induced by persistent dietary fat overload in skeletal muscle. PLoS One. 2018;13(5):e0195912. doi:10.1371/journal.pone.0195912.
11. Madkour MI, El-Serafi AT, Jahrami HA, et al. Ramadan diurnal intermittent fasting modulates SOD2, TFAM, Nrf2, and sirtuins (SIRT 1, SIRT3) gene expressions in subjects with overweight and obesity. Diabetes Res Clin Pract. 2019;155:107801. doi:10.1016/j.diabres.2019.107801.
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15. Intermittent fasting has benefits beyond weight loss. Cleveland Clinic. https://health.clevelandclinic.org/interested-fasting-health-get-facts-first/. Published October 23, 2015. Accessed February 18, 2020.
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