Circadian Fasting & Precursors to Heart Health

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As part of cultural or religious traditions, humans have practiced periodic fasting for thousands of years. Only in the past century has much of the population had easy access to excess calories every single day throughout their lifespans. This relatively recent eating pattern correlates with the onset of many chronic illnesses, including cardiovascular disease (CVD). On the other hand, intermittent fasting strategies, including time-restricted eating* interventions, have a range of health benefits, including the improvement of precursors to cardiovascular disease such as obesity, hypertension, dyslipidemia, and diabetes.1,2

Studies suggest that intermittent fasting treatments may improve health through multiple pathways, potentially reducing oxidative stress,2 enhancing mitochondrial health and DNA repair,1 and triggering autophagy,1 a cellular recycling system with a possible therapeutic role in some inflammatory diseases.3 And specific timing patterns of eating and fasting windows may lead to greater improvement of cardiometabolic markers.4

Time-restricted eating is a form of circadian fasting—a dietary pattern that optimizes circadian elements such as daily rhythms for insulin peaks and glucose tolerance5 by consuming food and beverages within a shortened window of time during the day, extending a person’s nightly fast to 12 hours or more. Intermittent fasting can be undertaken in many ways, with different durations. With longer fasting times (likely over 24 hours), autophagy may be improved. During autophagy, the body performs a “housecleaning” of sorts, removing damaged cells and pathogens, among other actions.6 This could be a beneficial process for improving immune function and helping patients with chronic inflammatory diseases,7 although this research is still very much developing.

Emerging research suggests that evening fasting (skipping dinner) may be more effective than morning fasting (skipping breakfast),8 and that eating fewer meals during the day may reduce disease incidence.9 Meal timing affects circadian rhythms, and late night eating may contribute to obesity more than food consumed at other times of the day.9 This may in part be due to the diurnal rhythm of glucose tolerance, which peaks in the mornings; some evidence shows that peak is lowered by early-phase time-restricted feeding.10

While there are limited large trials establishing an association between intermittent fasting interventions and improved cardiovascular disease outcomes, the available research suggests that in addition to reducing cardiovascular disease risk factors in healthy populations,2,4,11 time-restricted eating may also hold promise as a beneficial adjunctive therapy, improving cardiometabolic health for some patients with metabolic syndrome.12

Intermittent fasting may be beneficial in a range of cardiometabolic conditions:

  • In a case series with three patients, type 2 diabetes was reversed and insulin discontinued due to therapeutic fasting.13
  • During a study on Mormons in the US, periodic religious fasting was associated with a lower incidence of coronary artery disease.14
  • In patients with coronary artery disease, routine periodic fasting has been correlated with a lower incidence of type 2 diabetes.15
  • In patients with and without type 2 diabetes, intermittent fasting improved fatty liver index, a proxy for non-alcoholic fatty liver disease (NAFLD), significantly and rapidly.16
  • Intermittent fasting in overweight women led to improved fasting insulin, insulin resistance, and inflammatory markers. The intervention was well tolerated over six months.17
  • A systematic review concluded that more research is needed but that intermittent fasting shows promise for helping to treat patients with obesity, and no serious adverse effects were documented.18

Circadian Rhythms: Clinical Significance

The circadian rhythms of the body influence sleep-wake cycles, eating and digestion patterns, and biochemical and metabolic processes.19 Studies suggest that interruptions to these biological rhythms and erratic eating patterns may lead to an elevated risk for chronic conditions, including cardiovascular diseases.19-21 For example, consuming more calories at breakfast may yield better health outcomes,8 while late-night meals may contribute to cardiovascular disease precursors such as obesity.9 

Time-restricted feeding approaches consider these circadian elements, and in 2018, a small randomized controlled trial (RCT) with pre-diabetic participants was reportedly the first trial to investigate the impact of what researchers termed “early time-restricted eating.”22 This intervention involved a six-hour eating period, no caloric restrictions, and dinner consumed before 3 pm. The control group followed a 12-hour eating window, and after a five-week intervention, compared to controls, the treatment group had reduced insulin levels and blood pressure without any reported weight loss. In addition, the treatment group showed improved insulin sensitivity and beta cell responsiveness.22

Additional small clinical trials published in 2019 also investigated the cardiometabolic and other biological impacts of early time-restricted eating.10,23-24 Two of those studies included a six-hour feeding window of 8 am to 2 pm. Compared to the 12-hour control eating schedules, results indicated that the early time-restricted eating treatments:

  • Decreased fasting glucose levels.10
  • Altered lipid metabolism15 and increased fat oxidation.24
  • Increased metabolic flexibility, defined as the ability to switch between the oxidation of different substrates.24
  • Increased a sense of fullness, decreased the desire to eat, and had no impact on 24-hour energy expenditure.24

It is important to note that not everyone is a suitable candidate for fasting. Some preexisting conditions rule out fasting. Patients with a history of eating disorders need to be carefully considered; in one study, along with other factors, fasting was correlated with a later emergence of eating disorders in adolescent women with existing body dissatisfaction.25 Ramadan fasting has provided a window into the potential effects of unmonitored fasting (usually prohibiting liquids as well) on diabetic patients. Hypo- and hyperglycemia is a concern, as is thrombosis,26 but researchers do conclude that type 2 diabetics likely can fast safely, with precautions.27 High-quality studies on humans are still needed to determine long-term effects and to improve clinical confidence.28


Time-restricted eating interventions that optimize circadian elements have the potential to improve patient outcomes through addressing the precursors of cardiovascular diseases and improving cardiometabolic health. Specific eating windows and fasting lengths that yield the maximum health benefit continue to be studied; however, through the personalized approach of functional medicine care, flexible fasting strategies can be infused with personalized therapeutic nutritional interventions for each patient in order to create the most effective health treatment.

Nutrition and lifestyle strategies, including time-restricted eating, can positively impact cardiovascular outcomes. There are many different ways to fast, and each patient may have a different response. To learn more about the therapeutic effects of fasting and how to apply them, check out IFM’s Intermittent Fasting: Therapeutic Mechanisms & Clinical Applications. This course provides an evidence-based overview of several of the fasting methods and points of personalization for each patient’s unique health needs and goals.

*Of Note: Semantically, some experts define fasting as lasting 24 hours or more and therefore technically do not consider time-restricted eating a form of fasting.


Chronobiology: A Dynamic Field of Rhythm and Clock Genes

Fasting and Mitochondrial Health


  1. Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev. 2017;39:46-58. doi:1016/j.arr.2016.10.005
  2. Dong TA, Sandesara PB, Dhindsa DS, et al. Intermittent fasting: a heart healthy dietary pattern? Am J Med. 2020;133(8):901-907. doi:1016/j.amjmed.2020.03.030
  3. Qian M, Fang X, Wang X. Autophagy and inflammation. Clin Transl Med. 2017;6(1):24. doi:1186/s40169-017-0154-5
  4. Waldman HS, Renteria LI, McAllister MJ. Time-restricted feeding for the prevention of cardiometabolic diseases in high-stress occupations: a mechanistic review. Nutr Rev. 2020;78(6):459-464. doi:1093/nutrit/nuz090
  5. Poggiogalle E, Jamshed H, Peterson CM. Circadian regulation of glucose, lipid, and energy metabolism in humans. Metabolism. 2018;84:11-27. doi:1016/j.metabol.2017.11.017
  6. Bagherniya M, Butler AE, Barreto GE, Sahebkar A. The effect of fasting or calorie restriction on autophagy induction: a review of the literature. Ageing Res Rev. 2018;47:183-197. doi:1016/j.arr.2018.08.004
  7. Deretic V, Levine B. Autophagy balances inflammation in innate immunity. Autophagy. 2018;14(2):243-251. doi:1080/15548627.2017.1402992
  8. Nas A, Mirza N, Hägele F, et al. Impact of breakfast skipping compared with dinner skipping on regulation of energy balance and metabolic risk. Am J Clin Nutr. 2017;105(6):1351-1361. doi:3945/ajcn.116.151332
  9. Paoli A, Tinsley G, Bianco A, Moro T. The influence of meal frequency and timing on health in humans: the role of fasting. Nutrients. 2019;11(4):E719. doi:3390/nu11040719
  10.  Jamshed H, Beyl RA, Della Manna DL, Yang ES, Ravussin E, Peterson CM. Early time-restricted feeding improves 24-hour glucose levels and affects markers of the circadian clock, aging, and autophagy in humans. Nutrients. 2019;11(6):E1234. doi:3390/nu11061234
  11.  Moro T, Tinsley G, Bianco A, et al. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. J Transl Med. 2016;14(1):290. doi:1186/s12967-016-1044-0
  12.  Wilkinson MJ, Manoogian ENC, Zadourian A, et al. Ten-hour time-restricted eating reduces weight, blood pressure, and atherogenic lipids in patients with metabolic syndrome. Cell Metab. 2020;31(1):92-104.e5. doi:1016/j.cmet.2019.11.004
  13.  Furmli S, Elmasry R, Ramos M, Fung J. Therapeutic use of intermittent fasting for people with type 2 diabetes as an alternative to insulin. BMJ Case Rep. 2018;2018:bcr2017221854. doi:1136/bcr-2017-221854
  14.  Horne BD, May HT, Anderson JL, et al. Usefulness of routine periodic fasting to lower risk of coronary artery disease in patients undergoing coronary angiography. Am J Cardiol. 2008;102(7):814-819. doi:1016/j.amjcard.2008.05.021
  15.  Drinda S, Grundler F, Neumann T, et al. Effects of periodic fasting on fatty liver index—a prospective observational study. Nutrients. 2019;11(11):E2601. doi:3390/nu11112601
  16.  Harvie MN, Pegington M, Mattson MP, et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond). 2011;35(5):714-727. doi:1038/ijo.2010.171
  17.  Welton S, Minty R, O’Driscoll T, et al. Intermittent fasting and weight loss: systematic review. Can Fam Physician. 2020;66(2):117-125.
  18.  Circadian rhythms. National Institute of General Medical Sciences. Reviewed September 9, 2021. Accessed December 15, 2021.
  19.  Van Laake LW, Lüscher TF, Young ME. The circadian clock in cardiovascular regulation and disease: lessons from the Nobel Prize in Physiology or Medicine 2017. Eur Heart J. 2018;39(24):2326-2329. doi:1093/eurheartj/ehx775
  20.  Manoogian ENC, Panda S. Circadian rhythms, time-restricted feeding, and healthy aging. Ageing Res Rev. 2017;39:59-67. doi:1016/j.arr.2016.12.006
  21.  Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab. 2018;27(6):1212-1221.e3. doi:1016/j.cmet.2018.04.010
  22.  Hutchison AT, Regmi P, Manoogian ENC, et al. Time-restricted feeding improves glucose tolerance in men at risk for type 2 diabetes: a randomized crossover trial. Obesity (Silver Spring). 2019;27(5):724-732. doi:1002/oby.22449
  23.  Ravussin E, Beyl RA, Poggiogalle E, Hsia DS, Peterson CM. Early time-restricted feeding reduces appetite and increases fat oxidation but does not affect energy expenditure in humans. Obesity (Silver Spring). 2019;27(8):1244-1254. doi:1002/oby.22518
  24.  Stice E, Gau JM, Rohde P, Shaw H. Risk factors that predict future onset of each DSM-5eating disorder: predictive specificity in high-risk adolescent females. J Abnorm Psychol. 2017;126(1):38-51. doi:1037/abn0000219
  25.  V RA, Zargar AH. Diabetes control during Ramadan fasting. Cleve Clin J Med. 2017;84(5):352-356. doi:3949/ccjm.84a.16073
  26.  Badshah A, Haider I, Humayun M. Management of diabetes in Ramadan. J Ayub Med Coll Abbottabad. 2018;30(4):596-602.
  27.  Horne BD, Muhlestein JB, Anderson JL. Health effects of intermittent fasting: hormesis or harm? A systematic review. Am J Clin Nutr. 2015;102(2):464-470. doi:3945/ajcn.115.109553