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Intermittent Fasting: Current Evidence Reviewed March 29, 2020 Accepted April 6, 2020 Journal of Obesity & Metabolic Syndrome 2020;29:81-83 https://doi.org/10.7570/jomes20022 CROSSMARK_logo_3_Test 1 / 1 pISSN 2508-6235 Editorial eISSN 2508-7576 https://crossmark-cdn.crossref.org/widget/v2.0/logos/CROSSMARK_Color_square.svg 2017-03-16 Received March 17, 2020 Intermittent Fasting: Current Evidence Reviewed March 29, 2020 Accepted April 6, 2020 in Clinical Practice * Corresponding author Sang-Hoon Ahn So Hyun Kang1, Young Suk Park1,2, Sang-Hoon Ahn1,2,*, Hyung-Ho Kim1,2 1Department of Surgery, Seoul National University Bundang Hospital, Seongnam; 2Department of Surgery, Seoul National University College of Medicine, Seoul, Korea https://orcid.org/0000-0001-8827-3625 Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea Tel: +82-31-787-7106 Fax: +82-31-787-4078 E-mail: [email protected] Intermittent fasting (IF), or time-restricted feeding, is an emerg- blood insulin.4,6 de Cabo and Mattson4 illustrated in their review ing dietary intervention that restricts intake of food and energy for that stimulating autophagy while inhibiting the mammalian target a given period. Not only does this method restrict total caloric in- of rapamycin protein synthesis pathway can lead to removal of oxi- take, it also promotes metabolic homeostasis by supporting circa- datively damaged cells. In a review by Wahl et al.,7 IF was shown to dian feeding rhythms.1,2 Only in the most recent 200 years have hu- have positive effects on memory acquisition and cognitive behavior mans been able to access supplies of vast amounts of food and re- in rodent models. One possible hypothesis for this effect is produc- sources, which has caused a shift in disease patterns, particularly for tion of proinflammatory factors with glucose-based diets.8 The re- metabolic syndromes and obesity. The idea that reducing caloric duction of these proinflammatory factors may be beneficial for re- intake can result in evolutionary cellular responses for survival has ducing systemic inflammation and oxidative stress factors that play been an active research topic,3 but with the recent public awareness a role in development of atherosclerosis.9 and interest in IF, many clinical studies have been published more Several clinical studies, including some randomized control tri- recently. On December 2019, de Cabo and Mattson4 published a als, have been performed to analyze the effects of IF and caloric re- review article that discusses the mechanisms and current clinical striction in a wide range of applications. Although preclinical stud- evidence for IF. This review article discusses various broad-spec- ies have demonstrated reduction of insulin sensitivity after caloric trum benefits of IF, with a positive outlook for more clinical evi- restriction and periodic fasting,4,10 clinical studies have showed in- dence in the future. consistent results. The calorie restriction and cardiometabolic risk The most widely accepted theory behind the primary physiolog- (CALERIE) study11 is a phase 2, multicenter, randomized control ic response after IF is the switch of energy source from glucose to trial where 218 patients were allocated to either the 25% caloric re- triglycerides, which has also been termed as the “ketogenic diet.”5 stricting group (n= 143) or an ad libitum control group (n= 75). This metabolic switch increases mitochondrial stress resistance, an- In the restricting group, there was significant loss in body weight tioxidative defenses, and autophagy while reducing the amount of and reduction in other cardiometabolic factors such as low-density Copyright © 2020 Korean Society for the Study of Obesity This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. J Obes Metab Syndr 2020;29:81-83 http://www.jomes.org | 81 Kang SH, et al. Intermittent Fasting in Clinical Practice lipoprotein (LDL) cholesterol and blood pressure. Fasting glucose controversial, especially compared with the Enhanced Recovery was significantly reduced at the first year, but there was no signifi- After Surgery (ERAS) protocol, which is now being implemented cant reduction at the second year. However, there was a significant with good outcomes in various types of surgery.14 One of the popu- decrease in a surrogate marker for insulin resistance, which was es- lar components of the ERAS program is reducing preoperative timated by the homeostatic model assessment for insulin resistance fasting time to 6 hours and providing oral carbohydrate solutions (HOMA-IR). Another study by Marinac et al.8 evaluated the fre- for up to 2 hours before surgery—encouraging preoperative oral quency and circadian timing of feeding with metabolic syndrome nutrition. This theoretically reduces preoperative anxiety, and pa- and breast cancer risk in women and showed no association of tients transition into an anabolic state to benefit from postoperative HOMA-IR with evening calorie intake, eating frequency, or night- nutrition.15 The ERAS protocol is a comprehensive idea for reduc- time fasting duration. Recently, Wilkinson et al.2 published a single- ing surgical stress to promote faster recovery; however, it does not arm study of 19 patients with metabolic syndrome who were explore the idea of fasting alone. Thus, the current success of the mostly on statin and/or antihypertensive therapy. Patients were re- ERAS protocols may not necessarily be attributable to reduced stricted to a 10-hour period of feeding and were examined for body preoperative fasting, and additional well-designed control studies composition and other health metrics after 12 weeks. There was are needed to elucidate how preoperative fasting affects patient significant decrease in body weight, body fat, systolic/diastolic outcome. blood pressure, total cholesterol, and LDL-cholesterol. Although Despite all the emerging evidence, there are still some pitfalls there was a trend toward decrease of blood glucose and glycosylat- and practical difficulties to IF and caloric restriction that are con- ed hemoglobin (HbA1c) levels, there was no statistically significant tinuously being studied. First, physiologic studies have not yet benefit. However, in a subgroup analysis of patients with either ele- achieved consensus on the optimal timing for IF. Some studies vated fasting glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7%, there have used alternative day fasting, and some have used a daily time- was a significant reduction in HbA1c level (–0.22%±0.32%, restricted schedule. Although studies have shown that IF reduces P= 0.04). patient stress4 in the long-term, most patients find it stressful and IF acts as a stress signal stimulator, preconditioning cells before are reluctant to start restricting intake, reducing patient compliance. ischemic tissue injury.4 Mauro et al.12 compared rodent models Worldwide, especially in Korea, many people believe that skipping with a 3-day water-only fasting, 1 week protein-free fasting, and one of the three meals in a day will result in deterioration of health overnutrition (high-fat diet) diet protocol prior to vascular surgery. and nutritional balance. To address such underlying concerns, de Short-term, 3-day fasting before vascular surgery significantly at- Cabo and Mattson4 suggested that physicians provide adequate in- tenuated intimal hyperplasia and reduced ischemia-reperfusion formation and continual support to applicable patients. outcomes. A randomized control trial examined bariatric patients In this era where food is abundant, scientists must re-evaluate the who were scheduled to undergo gastric bypass surgery and com- notion that “more is better” when it comes to nutrition. Despite the pared a 14-day very low-calorie diet (VLCD) group with the ad li- amount exploration regarding IF in clinical practice, there are many bitum control group.13 Although there was no difference in opera- areas that have not yet been explored in well-designed clinical trials. tion time, the number of 30-day complications was higher in the Therefore, additional research and consideration are needed to op- control group than the VLCD group. Abdominal surgery increases timize patient outcomes. in difficulty with increasing body fat composition, and high amounts of visceral fat lead to unclean dissection of the body CONFLICTS OF INTEREST planes, resulting in an operative field prone to inflammation and fluid collection. In addition, high subcutaneous fat complicates The authors declare no conflict of interest. wound closure, resulting in more frequent wound complications. The possible benefits of IF before elective surgery are currently 82 | http://www.jomes.org J Obes Metab Syndr 2020;29:81-83 Kang SH, et al. Intermittent Fasting in Clinical Practice AUTHOR CONTRIBUTIONS 9. Moro T, Tinsley G, Bianco A, Marcolin G, Pacelli QF, Batta- glia G, et al. Effects of eight weeks of time-restricted feeding Study concept and design: SHK, SHA; drafting of the manu- (16/8) on basal metabolism, maximal strength, body compo- script: SHK, SHA; and critical revision of the manuscript: YSP, sition, inflammation, and cardiovascular risk factors in resis- SHA, HHK. tance-trained males. J Transl Med 2016;14:290. 10. Mattison JA, Colman RJ, Beasley TM, Allison DB, Kemnitz REFERENCES JW, Roth GS, et al. Caloric restriction improves health and survival of rhesus monkeys. Nat Commun 2017;8:14063. 1. Panda S. Circadian physiology of metabolism. Science 2016; 11. Kraus WE, Bhapkar M, Huffman KM, Pieper CF, Krupa Das S, 354:1008-15. Redman LM, et al. 2 Years of calorie restriction and cardio- 2. Wilkinson MJ, Manoogian EN, Zadourian A, Lo H, Fakhouri S, metabolic risk (CALERIE): exploratory outcomes of a multi- Shoghi A, et al. Ten-hour time-restricted eating reduces weight, centre, phase 2, randomised controlled trial. Lancet Diabetes blood pressure, and atherogenic lipids in patients with meta- Endocrinol 2019;7:673-83.
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