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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 daily excess calories 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, high blood pressure, dyslipidemia, and diabetes.^1,2

Intermittent Fasting, Time-Restricted Eating, & Cardiometabolic Health

Studies suggest that therapeutic fasting treatments may improve health through multiple pathways, potentially reducing oxidative stress,¹ enhancing mitochondrial health and DNA repair,^3,4 and triggering autophagy,⁵ a cellular recycling system that removes damaged cells and pathogens, among other actions.⁶ Intermittent fasting is a broad term used to describe food consumption cycles that alternate between periods of restricting calories and periods of not restricting calories. Different forms of 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.⁷ The medically supervised treatment included scheduled 24-hour fasts three times per week for several months.⁷
• During a prospective study (n=697 patients with and without type 2 diabetes), an intermittent fasting intervention that included periodic daily caloric restriction improved fatty liver index, a proxy for non-alcoholic fatty liver disease (NAFLD), significantly and rapidly.⁸
• A systematic review (n=27 clinical trials) concluded that more research is needed but that intermittent fasting approaches (i.e., 5:2 diet, time-restricted eating, alternate-day fasting) show promise for helping to treat patients with obesity, and no serious adverse effects were documented.⁹
• A randomized clinical trial (n=39 adult patients with metabolic syndrome) found that those patients in the intermittent fasting group following an alternate-day fasting treatment significantly reduced fat mass, oxidative stress, inflammatory biomarkers, and improved vasodilatory parameters compared to the control group.¹⁰ Study results also indicated that the fasting intervention increased the production of short-chain fatty acids.¹⁰

Specific timing patterns of eating and fasting windows may also lead to greater improvements of cardiometabolic markers.^11,12 Time-restricted eating (TRE) is an intermittent fasting approach that is a form of circadian fasting—a dietary pattern that optimizes circadian elements such as daily rhythms for insulin peaks and glucose tolerance 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. Research studies suggest that in addition to reducing cardiovascular disease risk factors in healthy populations,^13,14 circadian fasting may also hold promise as a beneficial adjunctive therapy, improving cardiometabolic health for some patients with conditions such as metabolic syndrome^15,16 and NAFLD.^17,18

As an example, in a 12-week randomized controlled trial (RCT), 45 middle-aged patients with NAFLD were randomized to either the intervention group (followed a daily circadian fasting/TRE pattern of 16-hour fasting and 8-hour feeding in addition to a low-sugar diet) or the control group (followed an isocaloric control diet based on traditional meal distribution and eating patterns).¹⁸ In addition to the reduction of body fat, body weight, waist circumference, body mass index, inflammatory markers, and total cholesterol, the intervention group also showed a clinically significant reduction in liver stiffness measurements.¹⁸

Circadian Rhythms & Early Time-Restricted Eating

The circadian rhythms of the body influence sleep-wake cycles, eating and digestion patterns, and biochemical and metabolic processes. Studies suggest that interruptions to these biological rhythms and erratic eating patterns may lead to an elevated risk for chronic conditions, including CVDs.^19,20 Meal timing affects circadian rhythms, and late night eating may contribute to CVD precursors such as obesity more than food consumed at other times of the day.²¹ 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 TRE.²²

In 2018, a small RCT with pre-diabetic participants was reportedly the first trial to investigate the impact of what researchers termed “early time-restricted eating.”²³ 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.²³

Additional clinical trials also investigated the cardiometabolic and other biological impacts of early TRE.^22,24-26 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.^22,24
• Altered lipid metabolism and increased fat oxidation.²⁵
• Increased metabolic flexibility, defined as the ability to switch between the oxidation of different substrates.²⁵
• Increased a sense of fullness, decreased the desire to eat, and had no impact on 24-hour energy expenditure.²⁵

Recent meta-analyses that have assessed early TRE interventions also have suggested that these approaches may have beneficial effects on health parameters such as body weight, fasting blood glucose, and insulin resistance measurements.^27,28

Personalization & Incorporating Fasting Into Therapeutic Food Plans

It is important to note that not everyone is a suitable candidate for fasting therapies. Some preexisting conditions rule out this intervention strategy for patients such as those who are pregnant, who have type 1 diabetes, or who have a history of or are at risk of developing an eating disorder. If, however, fasting is appropriate for a patient, different forms of fasting may be blended with therapeutic food plans to create an individualized nutrition intervention. Examples of fasting approaches include the following:

• Fasting: The willful abstinence from any caloric intake for an extended period that is greater than 24 hours. This practice usually includes water only, but some methods allow tea, coffee, and minerals. Of note, some experts only define fasting in this way and do not consider intermittent approaches as forms of fasting.
• Intermittent fasting: A broad term used to describe food consumption cycles that alternate between periods of restricting calories and periods of not restricting calories.
• Time-restricted eating/prolonged nightly fasting: Calories from food and beverages are consumed only during a shortened window of time daily, ranging from four to 12 hours. This is also called “prolonged nightly fasting,” which eliminates or reduces a person’s caloric intake at night, with an extended overnight fast that is greater than 10 hours.
• Alternate-day fasting: A cycle of a complete fast on one day and eating freely on the next day.
• Intermittent energy restriction: Consecutive or non-consecutive days of alternating very low-calorie intake (as low as 400 to 500 kcal) with days of normal calorie intake.
• 5:2 diet: Two consecutive or non-consecutive days of low-calorie intake (no more than 25% of an individual’s daily caloric requirement) coupled with five days of unrestricted eating.
• Calorie restriction: Daily caloric intake is reduced for an extended period without causing malnutrition, and meal frequency is maintained.
• Fasting-mimicking diet: A periodic, multiple-day (typically followed for five days), very low-calorie, low carbohydrate food plan designed to mimic a fasting state.

Conclusion

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 to create the most effective health treatment.

There are many ways to fast, and each patient may have a different response. Learn more about the therapeutic effects of fasting through IFM’s course, 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.

Related Content

Chronobiology: A Dynamic Field of Rhythm and Clock Genes

Fasting and Mitochondrial Health

Fasting and the Gut Microbiome: Exploring the Connection and Health Benefits

References

1. Yang F, Liu C, Liu X, et al. Effect of epidemic intermittent fasting on cardiometabolic risk factors: a systematic review and meta-analysis of randomized controlled trials. Front Nutr. 2021;8:669325. doi:3389/fnut.2021.669325
2. Obermayer A, Tripolt NJ, Pferschy PN, et al. Efficacy and safety of intermittent fasting in people with insulin-treated type 2 diabetes (INTERFAST-2)—a randomized controlled trial. Diabetes Care. 2023;46(2):463-468. doi:2337/dc22-1622
3. Lilja S, Stoll C, Krammer U, et al. Five days periodic fasting elevates levels of longevity related Christensenella and sirtuin expression in humans. Int J Mol Sci.2021;22(5):2331. doi:3390/ijms22052331
4. Madkour MI, T El-Serafi A, 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:1016/j.diabres.2019.107801
5. Qian J, Fang Y, Yuan N, et al. Innate immune remodeling by short-term intensive fasting. Aging Cell. 2021;20(11):e13507. doi:1111/acel.13507
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. 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
8. 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
9. Welton S, Minty R, O’Driscoll T, et al. Intermittent fasting and weight loss: systematic review. Can Fam Physician. 2020;66(2):117-125.
10.  Guo Y, Luo S, Ye Y, Yin S, Fan J, Xia M. Intermittent fasting improves cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients. J Clin Endocrinol Metab. 2021;106(1):64-79. doi:1210/clinem/dgaa644
11.  Xie Z, He Z, Ye Y, Mao Y. Effects of time-restricted feeding with different feeding windows on metabolic health: a systematic review of human studies. Nutrition. 2022;102:111764. doi:1016/j.nut.2022.111764
12.  Sun JC, Tan ZT, He CJ, Hu HL, Zhai CL, Qian G. Time-restricted eating with calorie restriction on weight loss and cardiometabolic risk: a systematic review and meta-analysis [published correction appears in Eur J Clin Nutr. 2023;77(11):1100]. Eur J Clin Nutr. 2023;77(11):1014-1025. doi:1038/s41430-023-01311-w
13.  Moon S, Kang J, Kim SH, et al. Beneficial effects of time-restricted eating on metabolic diseases: a systemic review and meta-analysis. Nutrients. 2020;12(5):1267. doi:3390/nu12051267
14.  Kang J, Ratamess NA, Faigenbaum AD, et al. Effect of time-restricted feeding on anthropometric, metabolic, and fitness parameters: a systematic review. J Am Nutr Assoc. 2022;41(8):810-825. doi:1080/07315724.2021.1958719
15.  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
16.  He M, Wang J, Liang Q, et al. Time-restricted eating with or without low-carbohydrate diet reduces visceral fat and improves metabolic syndrome: a randomized trial. Cell Rep Med. 2022;3(10):100777. doi:1016/j.xcrm.2022.100777
17.  Cai H, Qin YL, Shi ZY, et al. Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: a randomised controlled trial. BMC Gastroenterol. 2019;19(1):219. doi:1186/s12876-019-1132-8
18.  Kord-Varkaneh H, Salehi-Sahlabadi A, Tinsley GM, Santos HO, Hekmatdoost A. Effects of time-restricted feeding (16/8) combined with a low-sugar diet on the management of non-alcoholic fatty liver disease: a randomized controlled trial. Nutrition. 2023;105:111847. doi:1016/j.nut.2022.111847
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.  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
22.  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
23.  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
24.  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
25.  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
26.  Teong XT, Liu K, Vincent AD, et al. Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial. Nat Med. 2023;29(4):963-972. doi:1038/s41591-023-02287-7
27.  Pureza IROM, Macena ML, da Silva Junior AE, Praxedes DRS, Vasconcelos LGL, Bueno NB. Effect of early time-restricted feeding on the metabolic profile of adults with excess weight: a systematic review with meta-analysis. Clin Nutr. 2021;40(4):1788-1799. doi:1016/j.clnu.2020.10.031
28.  Liu J, Yi P, Liu F. The effect of early time-restricted eating vs later time-restricted eating on weight loss and metabolic health. J Clin Endocrinol Metab. 2023;108(7):1824-1834. doi:1210/clinem/dgad036