Does Intermittent Fasting Work?

When it comes to diet and nutrition, many trends come and go, but one that may have staying power is intermittent fasting.

This unique diet does not focus on what individuals eat but when they eat. Intermittent fasting contrasts with the typical eating pattern of most Americans, who eat throughout their waking hours.¹ When individuals eat 3 meals a day plus snacks without exercising, their fat stores are not being burned. Intermittent fasting has several regimens (Table^2,3), but the basic premise involves taking periodic breaks from eating.¹

Intermittent-fasting practices have demonstrated short-term effects on patients’ metabolic health, with data in recent literature indicating significant reductions in cardiometabolic risk, waist circumference, and weight.^4,5 These findings were reproduced in both calorie-restricted and eucaloric intermittent-fasting regimens, indicating a physiological benefit independent of reduced caloric intake.⁴ Additionally, intermittent fasting has been shown to decrease levels of low-density lipoproteins, enhance insulin sensitivity, and increase high-density lipoprotein cholesterol.⁶

The 3 main theories proposed to explain the metabolic effects of intermittent fasting include the circadian rhythm hypothesis, the ketosis theory, and the oxidative stress hypothesis.⁴

Ketosis is the metabolic process that occurs when the body has depleted its glucose supply and starts burning stored fat for energy. The ketosis theory suggests that intermittent fasting reduces total calorie intake, causing a metabolic shift that increases fat utilization and insulin sensitivity. This leads to more efficient fat metabolism and reduced fat storage. As a result, intermittent fasting optimizes body fat, waist circumference, and weight loss.⁴ The ketosis theory suggests short-term benefits of intermittent fasting, whereas the circadian rhythm and oxidative stress hypotheses suggest long-term benefits.⁴

Oxidative stress damages cellular structures and can exacerbate and/or promote the development of metabolic-related health problems.³ The oxidative stress theory postulates that decreased energy intake through intermittent fasting leads to a decreased production of reactive oxygen species by the mitochondria and increased antioxidant activity.⁴ This process results in diminished cellular inflammation and increased autophagy.⁴ Reduction of systemic inflammation decreases the risk of long-term conditions, such as metabolic syndrome.⁴

The relationship between intermittent fasting and metabolic regulation may also involve the circadian system. Organisms have evolved to develop an endogenous circadian clock by restricting their activity to the day or the night to ensure physiological processes are performed at optimal times.⁴ The time of day is important for integrating metabolism with physiological processes, such as hormonal secretion. Results from recent literature on circadian rhythms have demonstrated a diurnal variation in blood glucose levels and insulin release. This indicates that metabolic response to calorie consumption may vary depending on the time of day and therefore is independent of the amount of food eaten.⁴ Time-restricted eating involves limited feeding windows that allow for synchronization of mealtimes with the circadian clock and therefore optimizes metabolic function.⁴ Furthermore, adiponectin, a key circadian system regulator that is linked to better glycemic control and insulin sensitivity, increases after intermittent fasting in physically active individuals.⁴

Many functions of the gastrointestinal tract, including blood flow and gastric emptying, exhibit robust circadian rhythms. The gut microbiome is highly dynamic, as it exhibits daily cyclical fluctuations in composition. Intermittent fasting may directly affect the gut microbiome. The daily feeding and fasting rhythms associated with intermittent fasting influence the diversity of the gut microbiome, which further affects host metabolism. Extended fasting periods may lead to reduced gut permeability and systemic inflammation, both of which are typically elevated in obesity.²

Conclusion

Because of the increasing prevalence of obesity and overweight individuals in the United States, many are searching for effective weight-loss methods. Intermittent fasting has demonstrated numerous long- and short-term health benefits and leads to improved awareness of eating habits and hunger. However, intermittent fasting may not be appropriate for every individual, and it is important to discuss the idea with a provider before starting a fasting regimen.

References

1. Intermittent fasting: what is it, and how does it work? Johns Hopkins Medicine. Accessed April 18, 2023. https://www.hopkinsmedicine.org/health/wellness-and-prevention/intermittent-fasting-what-is-it-and-how-does-it-work

2. Stockman MC, Thomas D, Burke J, Apovian CM. Intermittent fasting: is the wait worth the weight? Curr Obes Rep. 2018;7(2):172-185. doi:10.1007/s13679-018-0308-9

3. Mohr AE, McEvoy C, Sears DD, Arciero PJ, Sweazea KL. Impact of intermittent fasting regimens on circulating markers of oxidative stress in overweight and obese humans: a systematic review of randomized controlled trials. Adv Redox Res. 2021;3:100026. doi:10.1016/j.arres.2021.100026

4. Mandal S, Simmons N, Awan S, Chamari K, Ahmed I. Intermittent fasting: eating by the clock for health and exercise performance. BMJ Open Sport Exerc Med. 2022;8(1):e001206. doi:10.1136/bmjsem-2021-001206

5. Volpe SL. Intermittent fasting – what is it and does it work? ACSM Health Fit J. 2019;23(1):34-36. doi:10.1249/fit.0000000000000444

6. Dong TA, Sandesara PB, Dhindsa DS, et al. Intermittent fasting: a heart healthy dietary pattern? Am J Med. 2020;133(8):901-907. doi:10.1016/j.amjmed.2020.03.030The daily feeding and fasting rhythms associated with intermittent fasting influence the diversity of the gut microbiome, which further affects host metabolism.© Aleksandr / Adobe Stock

About the Author

Kirsten Werner is a 2023 PharmD candidate at the University of Connecticut School of Pharmacyin Storrs.