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Cardiovascular diseases and atherosclerosis can be prevented and treated by means of periodic fasting and caloric restriction. Scientific evidence.


Caloric restriction delays cardiac ageing in rats: role of mitochondria.
Cardiovasc Res. 2010 Nov 1;88(2):267-76. Epub 2010 Aug 25.
Niemann B, Chen Y, Issa H, Silber RE, Rohrbach S.
Department of Cardiothoracic Surgery, Martin Luther University Halle-Wittenberg, Germany.
Abstract:
AIMS: We tested whether long-term caloric restriction (CR) corrects pre-existing manifestations of cardiac ageing in rats.
METHODS AND RESULTS: The age-specific effects of CR (-40%, 6 months) on mortality, left ventricular (LV) function, mitochondrial function, oxidative damage, and apoptosis were analysed in young (6 + 6 months) and senescent rats (24 + 6 months). CR in senescent rats significantly reduced mortality. LV and cardiomyocyte hypertrophy were reduced together with the mRNA expression and plasma concentrations of overload indicators BNP/ANP. Mitochondrial function was improved, resulting in lower oxidative damage and apoptotic activation. In particular, the pro-apoptotic Bcl-xS/Bcl-xL isoform pattern, mitochondrial translocation of Bax, release of cytochrome C into cytosol, and caspase-9 activation were reduced in comparison to age-matched rats on the control diet. However, CR resulted only in minor changes in young rats. Serum obtained from old control or CR rats was used for in vitro experiments. H9C2 cardiomyoblasts and adult rat ventricular cardiomyocytes preconditioned with CR serum demonstrated a low Bcl-xS/Bcl-xL ratio. H9C2 cells were resistant against H(2)O(2)-mediated loss of mitochondrial membrane potential, apoptosis activation, and reduced cell viability. Thus, beneficial effects of CR are mediated through circulating factors and can be mimicked with CR serum. However, this protection critically depended on a high Bcl-xL protein expression as seen after siRNA-mediated Bcl-xL knockdown.
CONCLUSION: CR is cardioprotective in senescent myocardium by correcting pre-existing mitochondrial dysfunction and apoptotic activation and by preventing deterioration in LV function. Therefore, interventions that mimic these effects of CR may represent an additional therapeutic option for the aged or failing heart.

Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults.
Varady KA, Bhutani S, Church EC, Klempel MC.
Am J Clin Nutr. 2009 Nov;90(5):1138-43. Epub 2009 Sep 30.
Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, 
Abstract:
BACKGROUND: The ability of modified alternate-day fasting (ADF; ie, consuming 25% of energy needs on the fast day and ad libitum food intake on the following day) to facilitate weight loss and lower vascular disease risk in obese individuals remains unknown.
OBJECTIVE: This study examined the effects of ADF that is administered under controlled compared with self-implemented conditions on body weight and coronary artery disease (CAD) risk indicators in obese adults.
DESIGN: Sixteen obese subjects (12 women, 4 men) completed a 10-wk trial, which consisted of 3 phases: 1) a 2-wk control phase, 2) a 4-wk weight loss/ADF controlled food intake phase, and 3) a 4-wk weight loss/ADF self-selected food intake phase.
RESULTS: Dietary adherence remained high throughout the controlled food intake phase (days adherent: 86%) and the self-selected food intake phase (days adherent: 89%). The rate of weight loss remained constant during controlled food intake (0.67 +/- 0.1 kg/wk) and self-selected food intake phases (0.68 +/- 0.1 kg/wk). Body weight decreased (P < 0.001) by 5.6 +/- 1.0 kg (5.8 +/- 1.1%) after 8 wk of diet. Percentage body fat decreased (P < 0.01) from 45 +/- 2% to 42 +/- 2%. Total cholesterol, LDL cholesterol, and triacylglycerol concentrations decreased (P < 0.01) by 21 +/- 4%, 25 +/- 10%, and 32 +/- 6%, respectively, after 8 wk of ADF, whereas HDL cholesterol remained unchanged. Systolic blood pressure decreased (P < 0.05) from 124 +/- 5 to 116 +/- 3 mm Hg.
CONCLUSION: These findings suggest that ADF is a viable diet option to help obese individuals lose weight and decrease CAD risk. This trial was registered at clinicaltrials.gov as UIC-004-2009.

 

 

Alternate-day fasting reduces global cell proliferation rates independently of dietary fat content in mice.
Varady KA, Roohk DJ, Bruss M, Hellerstein MK.
Nutrition. 2009 Apr;25(4):486-91. Epub 2008 Dec 11.
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, California, USA.
Abstract:
OBJECTIVE: Cell proliferation rates represent a central element in the promotional phase of carcinogenesis. Modified alternate-day fasting (ADF), i.e., a partial 24-h fast alternated with 24-h ad libitum feeding, reduces global cell proliferation rates on a low-fat (LF) diet. Because the majority of Americans consume a diet that is high in fat, testing the antiproliferative ability of ADF on a high-fat (HF) diet is important in terms of diet tolerability in humans. Accordingly, we examined the effects of 85% restriction on the fast day (ADF-85%) with an LF or HF background diet on proliferation rates of various tissues.
METHODS: In a 4-wk study, male C57BL/6J mice were randomized to one of three groups: 1) ADF-85%-LF, 2) ADF-85%-HF, or 3) control.
RESULTS: Body weights of the ADF mice were similar to that of controls throughout the study. A hyperphagic response (P < 0.001) was noted only in the ADF-85%-LF group ( approximately 55% more food consumed on the feed day than controls). No differences were noted for mean energy intake between ADF groups on feed or fast days. Equivalent reductions (P < 0.01) in epidermal, prostate, liver, and splenic T-cell proliferation rates were observed in both ADF groups versus controls. Plasma insulin-like growth factor-1 levels decreased (P < 0.05) similarly in both ADF groups. Insulin-like growth factor-1 mRNA levels were not affected by either treatment.
CONCLUSION: These findings indicate that ADF has an antiproliferative effect over a wide range of fat intakes, which may enhance adherence to ADF in humans.

 

 

The effects of three-week fasting diet on blood pressure, lipid profile and glucoregulation in extremely obese patients
2007 Jul-aug: 135 (7-8): 440-6
Beleslin B, Ciri J, Zarkovi M, Vujov S, Trbojevi B, Drezgi M.
INTRODUCTION: Obesity is often accompanied by a number of complications including diabetes mellitus and cardiovascular diseases. Elevated blood pressure and lipids, as well as deterioration of glucoregulation are attributed, as the most significant factors, to development of diabetes mellitus and cardiovascular complications in obese patients. OBJECTIVE: The aim of our study was to evaluate the effects of a fasting diet on blood pressure, lipid profile and glucoregulatory parameters. METHOD: We included 110 patients (33 male and 77 female; mean age 35 +/- 1 years, body weight 131.7 +/- 2.6 kg, body mass index 45.4 +/- 0.8 kg/m2) who were hospitalized for three weeks for the treatment of extreme obesity with the fasting diet. At the beginning, during, and at the end of this period, we evaluated changes in blood pressure, lipid profile, as well as parameters of glucoregulation including glycaemia, insulinaemia, and insulin sensitivity by HOMA. Oral glucose tolerance test (OGTT) was performed in all patients at the beginning and at the end of the fasting diet. RESULTS: During the fasting diet, the body weight decreased from 131.7 +/- 2.6 kg to 117.7 +/- 2.4 kg (p < 0.001), the body mass index decreased from 45.4 +/- 0.8 kg/m2 to 40.8 +/- 0.8 kg/m2 (p < 0.001), and both systolic and diastolic blood pressure significantly declined (143 +/- 2 vs. 132 +/- 2 mm Hg, p < 0.001; 92 +/- 2 vs. 85 +/- 2 mm Hg, p < 0.001). In addition, the fasting diet produced a significant decrease in total cholesterol, LDL cholesterol, triglycerides, as well as basal glycaemia and insulinaemia (p < 0.001) Before the fasting diet, OGTT was normal in 76% of patients, whereas 21% of patients showed glucose intolerance, and 4% of patients diabetes mellitus. After the fasting diet, OGTT was normal in 88% of patients, whereas 12% of patients still had signs of glucose intolerance (p < 0.05). In addition, insulin resistance significantly (p < 0.05) increased from 54 +/- 6% to 89 +/- 13% after the fasting diet. CONCLUSION: The three-week fasting diet in extremely obese patients produced a significant decrease and normalization of blood pressure, decrease in lipids, and improvement in glucoregulation including the increase in insulin sensitivity.

Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems.
J Nutr Biochem. 2005 Mar;16(3):129-37.
Mattson MP, Wan R.
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA. 
Intermittent fasting (IF; reduced meal frequency) and caloric restriction (CR) extend lifespan and increase resistance to age-related diseases in rodents and monkeys and improve the health of overweight humans. Both IF and CR enhance cardiovascular and brain functions and improve several risk factors for coronary artery disease and stroke including a reduction in blood pressure and increased insulin sensitivity. Cardiovascular stress adaptation is improved and heart rate variability is increased in rodents maintained on an IF or a CR diet. Moreover, rodents maintained on an IF regimen exhibit increased resistance of heart and brain cells to ischemic injury in experimental models of myocardial infarction and stroke. The beneficial effects of IF and CR result from at least two mechanisms--reduced oxidative damage and increased cellular stress resistance. Recent findings suggest that some of the beneficial effects of IF on both the cardiovascular system and the brain are mediated by brain-derived neurotrophic factor signaling in the brain. Interestingly, cellular and molecular effects of IF and CR on the cardiovascular system and the brain are similar to those of regular physical exercise, suggesting shared mechanisms. A better understanding of the cellular and molecular mechanisms by which IF and CR affect the blood vessels and heart and brain cells will likely lead to novel preventative and therapeutic strategies for extending health span.
 
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