Cardioprotective Effects of Intermittent Fasting

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China

*Corresponding Author:

Hongxin Zhu
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders
Ministry of Education, Shanghai Jiao Tong University, Shanghai, PR China
Tel: 862134207232
E-mail: hxzhu@sjtu.edu.cn

Received date: February 20, 2017; Accepted date: March 04, 2017; Published date: March 08, 2017

Citation: Zhu H, He L (2017) Cardioprotective Effects of Intermittent Fasting. J Clin Diagn Res 5:138. doi: 10.4172/2376-0311.1000138

Copyright: © 2017 Zhu H. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

Calorie restriction, a dietary regimen reducing energy intake without causing malnutrition, prolongs lifespan and exerts medical and health benefits such as lowering metabolic risk factors for chronic diseases and ameliorating chronic conditions. Intermittent fasting (IF), a type of calorie restriction regimen, has attracted particular attention as it is cost-effective and more accessible while exerting the same or even enhanced beneficial effects on health and disease in laboratory animals and humans. In this review, we focus on the protective effects of IF on several types of heart diseases including myocardial ischemic injury, age-related cardiac hypertrophy, doxorubicin-induced cardiotoxicity and coronary heart disease risk factors. The findings summarized here implicate IF as a non-pharmacological, non-genetic preventive or therapeutic intervention for certain types of heart disease.

Keywords

Intermittent fasting; Heart disease; Calorie restriction; Cardiac injury

Introduction

Calorie restriction, defined as a dietary regimen reducing energy intake without causing malnutrition, has been shown to enhance physiological health, reduce risk factors for chronic disease and improve chronic conditions [1,2]. Given the fact that intermittent fasting (IF), a form of calorie restriction regimen, is cost-effective and more accessible while exerting the same or even enhanced health benefits, it has attracted particular attention [3,4]. The most common way to undertake IF is that the individuals are completely fasted or severely restrict their food intake every other day, which also termed alternate-day fasting [5]. Another common strategy for IF is that energy uptake is severely restricted for one day or two non-consecutive days each week with or without daily calorie restriction [6]. IF has long been considered a potential preventive or therapeutic intervention for a variety of diseases such as cancer, neurodegenerative disorders, metabolic disease and cardiovascular disease [3]. Here we update the evidences regarding cardioprotective effects of IF in experimental animal models and humans.

IF and Myocardial Ischemic Injury

In rat models of myocardial infarction, IF protects the hearts from cardiac injury as manifested by reduced infarct size, decreased apoptotic myocytes and inflammation; in addition, IF attenuates post-myocardial infarction cardiac remodelling [7]. The beneficial effects are associated with increased serum adiponectin levels, which have been shown to protect the heart from ischemic injury [8,9]. In a rat model of chronic myocardial ischemia, IF improves the survival of rats with chronic heart failure, attenuates cardiac remodelling, improves cardiac function, stimulates angiogensis and reduces apoptotic cell death in the border zone of the ischemic hearts [10]. During ischemia-reperfusion, IF protects against cardiac injury in mice through restoration of impaired autophagic flux by stimulating nuclear translocation of TFEB, a master regulator of autophagy-lysosome gene expression networks [11]. Therefore, IF confers protection to the heart against ischemic injury in experimental animal models.

IF and Age-Related Cardiac Hypertrophy

IF improves markers for age-related cardiac hypertrophy and heart failure in rats including increased cardiac sarcomeric α-actin, β-MHC and elevated BNP in the heart and plasma. Moreover, IF ameliorates cardiac parameters including left ventricle weight, left ventricle weight/ body weight and cross-sectional area of individual cardiomyocyte, which are increased during ageing. The beneficial effects of IF in the ageing heart are achieved through restoring overactivated ERK1/2 and PI3Kγ signalling, both of which are associated with pathological cardiac hypertrophy [12]. In addition, IF is able to attenuate oxidative stress, fibrosis and inflammation in the ageing rat heart [13].

IF and Doxorubicin-Induced Cardiotoxicity

Doxorubicin is one of the most effective anti-neoplasm drugs. However, its clinical use is limited by potential cardiotoxicity. We and others have recently shown that autophagic flux is impaired in the mouse models of doxorubicin-induced cardiotoxicity, which contributes to heart injury [14-16]. Moreover, we have shown that IF is capable of restoring autophagic flux and ameliorating pathological alterations including increased cytoplasmic vacuolization, fibrosis, apoptosis and generation of reactive oxygen species in both acute and chronic doxorubicin cardiotoxicity [16]. Thus, IF could serve as a promising strategy for the prevention and control of doxorubicin-induced cardiotoxicity.

IF and Coronary Heart Disease Risk Factors

IF is able to alter spectral analysis of blood pressure and heart rate variability and reduce insulin levels in rats, which are risk factors for coronary heart disease [17,18]. IF also lowers coronary heart disease risk factors in humans. For instance, IF improves indicators of coronary heart disease in obese men and women including reducing body weight, waist circumference, fat mass, low-density lipoprotein cholesterol (LDL-C) and triacylglycerol [19]. In addition, IF-calorie restriction with liquid diet is more capable of reducing risk factors for coronary heart disease compared with IF-calorie restriction without liquid diet in obese women [20,21]. IF with high-protein and low-calorie diet reduces body weight, BMI, blood lipids and enhances arterial compliance in obese men and women [22]. Reduction of coronary heart disease risk factors by IF is associated with modulations of adipokines [19,21].

Conclusions

Caloric restriction exerts diverse beneficial effects on health and chronic conditions in animal models and humans. However, long-term caloric restriction is difficult to sustain. Although calorie restriction mimetics are more practical, IF offers a more accessible and cost-effective intervention to be realized in humans, and thus receives considerable attention. Importantly, IF has been shown to improve ischemic cardiac injury, age-related cardiac hypertrophy, doxorubicin-induced cardiotoxicity and risk factors for coronary heart disease. Therefore, IF may be considered as a potential intervention for certain forms of human heart disease. However, there are some limitations in current research on cardioprotection of IF in terms of practical applicability. First, IF is not without cardiac adverse effects as reduced diastolic compliance and diminished systolic reserve induced by chronic IF in animal models have been reported [23]. Second, the beneficial effects of IF on myocardial ischemic injury, age-related cardiac hypertrophy and doxorubicin-induced cardiotoxicity have only been shown in preclinical studies and it remains unknown if the results can be translated to humans. Third, although more sustainable, ethic issue should be considered for the execution of long-term IF in humans. Thus, medically supervised clinical trials should be designed and conducted to optimize fasting procedures to confer cardioprotection while minimizing the potential side effects. Nevertheless, IF represents a promising non-pharmacological, non-genetic preventive or therapeutic strategy for several types of heart disease.

References

1. Omodei D, Fontana L (2011) Calorie restriction and prevention of age-associated chronic disease.FEBS Lett585:1537-1542.
2. Most J, Tosti V, Redman LM, Fontana L (2016) Calorie restriction in humans: An update.Ageing Res Rev  pii: S1568-1637(16)30183-0.
3. Mattson MP, Longo VD, Harvie M (2016) Impact of intermittent fasting on health and disease processes. Ageing Res Rev pii: S1568-1637(16)30251-3.
4. Mattson MP, Wan R (2005) Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. J Nutr Biochem 16:129-137.
5. Varady KA, Hellerstein MK (2007) Alternate-day fasting and chronic disease prevention: a review of human and animal trials. Am J Clin Nutr 86: 7-13.
6. Harvie MN, Pegington M, Mattson MP, Frystyk J, Dillon B, et al. (2011) 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) 35:714-727.
7. Ahmet I, Wan R, Mattson MP, Lakatta EG, Talan M (2005) Cardio protection by intermittent fasting in rats. Circulation 112:3115-3121.
8. Wan R, Ahmet I, Brown M, Cheng A, Kamimura N (2010) Cardioprotective effect of intermittent fasting is associated with an elevation of adiponectin levels in rats. Nutr Biochem21:413-417.
9. Ouchi N, Shibata R, Walsh K (2006) Targeting adiponectin for cardioprotection.Expert Opin Ther Targets10:573-581.
10. Katare RG, Kakinuma Y, Arikawa M, Yamasaki F, Sato T (2009)Chronic intermittent fasting improves the survival following large myocardial ischemia by activation of BDNF/VEGF/PI3K signaling pathway. J Mol Cell Cardiol 46:405-412.
11. Godar RJ, Ma X, Liu H, Murphy JT, Weinheimer CJ (2015) Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury. Autophagy 11: 1537-1560.
12. Castello L, Maina M, Testa G, Cavallini G, Biasi F, et al. (2011) Alternate-day fasting reverses the age-associated hypertrophy phenotype in rat heart by influencing the ERK and PI3K signaling pathways. Mech Ageing Dev 132:305-314.
13. Castello L, Froio T, Maina M, Cavallini G, Biasi F, et al. (2010)Alternate-day fasting protects the rat heart against age-induced inflammation and fibrosis by inhibiting oxidative damage and NF-kB activation. Free Radic Biol Med48:47-54.
14. Li DL, Wang ZV, Ding G, Tan W, Luo X, et al. (2016)Doxorubicin blocks cardiomyocyte autophagic flux by inhibiting lysosome acidification. Circulation133:1668-1687.
15. Dirks-Naylor AJ (2013) The role of autophagy in doxorubicin-induced cardiotoxicity. Life Sci 93: 913-916.
16. Lin An, Xiao-wen Hu, Shasha Zhang, Xiaowen Hu, Zongpei Song, et al. (2017) UVRAG deficiency exacerbates doxorubicin-induced cardiotoxicity. Sci Rep 7: 43251.
17. Wan R, Camandola S, Mattson MP (2003)Intermittent fasting and dietary supplementation with 2-deoxy-D-glucose improve functional and metabolic cardiovascular risk factors in rats. FASEB J17:1133-1144.
18. Mager DE, Wan R, Brown M, Cheng A, Wareski P, et al. (2006) Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats. FASEB J20:631-637.
19. Bhutani S, Klempel MC, Berger RA, Varady KA (2010)Improvements in coronary heart disease risk indicators by alternate-day fasting involve adipose tissue modulations. Obesity (Silver Spring) 18:2152-2159.
20. Klempel MC, Kroeger CM, Bhutani S, Trepanowski JF, Varady KA (2012) Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. Nutr J11:98.
21. Kroeger CM, Klempel MC, Bhutani S, Trepanowski JF, Tangney CC, et al. (2012) Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations. Nutr Metab (Lond)9:98.
22. Zuo L, He F, Tinsley GM, Pannell BK, Ward E, et al. (2016)Comparison of high-protein, intermittent fasting low-calorie diet and heart healthy diet for vascular health of the obese. Front Physiol7:350.
23. Ahmet I, Wan R, Mattson MP, Lakatta EG, Talan MI (2010) Chronic alternate-day fasting results in reduced diastolic compliance and diminished systolic reserve in rats. J Card Fail16:843-853.