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.

Intermittent versus on-demand use of a very low calorie diet: a randomized 2-year clinical trial.?
J Intern Med. 2003 Apr;253(4):463-71
Lantz H, Peltonen M, Agren L, Torgerson JS.
Department of Body Composition and Metabolism, Sahlgrenska University Hospital, Goteborg, Sweden.

VLCD-induced weight loss improves heart rate variability in moderately obese Japanese.
CExp Biol Med (Maywood) 2001 May;226(5):440-5?
Akehi Y, Yoshimatsu H, Kurokawa M, Sakata T, Eto H, Ito S, Ono J.
Laboratory Medicine, School of Medicine, Fukuoka University, Japan.     To evaluate the effects of weight reduction on the autonomic nervous system in obese patients, we investigated heart rate variability (HRV) based on 24-hr ambulatory electrocardiogram (ECG) recordings before and after weight reduction. To aim for weight reduction, 16 obese patients were treated with the very-low-calorie conventional Japanese diet (VLCD-CJ) therapy combined with behavior therapy. Percent weight reduction was 17.8% +/- 1.5% (means +/- SEM), but mean blood pressure did not change significantly after VLCD-CJ therapy. The mean normal R-R interval (mNN) of the 24-hr ECG and all other five time-domain indices increased after weight reduction. Spectral analysis revealed that weight reduction increased the high frequency (HF) component, but decreased the ratio of low to high (LF/HF) components. Rate of change in mNN or HF correlated positively with reduction rate of body mass index, but not that in LF/HF. Analysis of daily fluctuations in each HRV parameter showed that significant improvement after weight loss occurred mainly during the nocturnal period, but an HF component was improved throughout the day and night periods. These findings indicate that functional impairment of the autonomic nervous system in obese subjects, particularly in the nocturnal period, is improved by effective weight reduction after VLCD-CJ therapy.?

Calorie restriction attenuates inflammatory responses to myocardial ischemia-reperfusion injury.
Am J Physiol Heart Circ Physiol 2001 May;280(5):H2094-102?
Colcombe SJ, Erickson KI, Raz N, Webb AG, Cohen NJ, McAuley E, Kramer AF.?
Division of Cardiology, University of Texas Health Science Center, San Antonio, 78229-3900, Texas, USA.  The life-prolonging effects of calorie restriction (CR) may be due to reduced damage from cumulative oxidative stress. Our goal was to determine the long-term effects of moderate dietary CR on the myocardial response to reperfusion after a single episode of sublethal ischemia. Male Fisher 344 rats were fed either an ad libitum (AL) or CR (40% less calories) diet. At age 12 mo the animals were anaesthetized and subjected to thoracotomy and a 15-min left-anterior descending coronary artery occlusion. The hearts were reperfused for various periods. GSH and GSSG levels, nuclear factor-kappaB (NF-kappaB) DNA binding activity, cytokine, and antioxidant enzyme _expression were assessed in the ischemic zones. Sham-operated animals served as controls. Compared with the AL diet, chronic CR limited oxidative stress as seen by rapid recovery in GSH levels in previously ischemic myocardium. CR reduced DNA binding activity of NF-kappaB. The kappaB-responsive cytokines interleukin-1beta and tumor necrosis factor-alpha were transiently expressed in the CR group but persisted longer in the AL group. Furthermore, _expression of manganese superoxide dismutase, a key antioxidant enzyme, was significantly delayed in the AL group. Collectively these data indicate that CR significantly attenuates myocardial oxidative stress and the postischemic inflammatory response.

Weight loss with very-low-calorie diet and cardiovascular risk factors in moderately obese women: one-year follow-up study including ambulatory blood pressure monitoring.
Int J Obes Relat Metab Disord 1998 Jul;22(7):661-6?
Pekkarinen T; Takala I; Mustajoki P. Department of Medicine, Helsinki University Hospital, Finland.

 OBJECTIVES: To compare two different very low calorie diet (VLCD)-based weight maintenance strategies. DESIGN AND SETTING: A randomized 2-year clinical trial performed at the Department of Body Composition and Metabolism, Sahlgrenska University Hospital, Sweden. SUBJECTS: A total of 334 patients, body mass index (BMI) >30 kg m-2, aged 18-60 years. INTERVENTIONS: All the patients started with 16 VLCD weeks. Subjects in the intermittent group were then scheduled to use VLCD for 2 weeks every third month, whilst patients in the on-demand group were instructed to use VLCD whenever their body weight passed an individualized cut-off level. Irrespective of the treatment group, all the subjects were recommended a hypocaloric diet during VLCD-free periods. MAIN OUTCOME MEASURES: Changes in body weight, body composition, anthropometric variables and cardiovascular risk factors. RESULTS: Completers in both groups maintained highly significant weight losses after 2 years: 7.0 +/- 11.0 kg (6.2 +/- 9.5%) in the intermittent group and 9.1 +/- 9.7 kg (7.7 +/- 8.1%) in the on-demand group (P < 0.001, ns between groups). Male completers in the on-demand group lost significantly more weight than men in the intermittent group, 14.5 +/- 11.0 kg vs. 4.0 +/- 10.5 kg, respectively (P < 0.01). Most cardiovascular risk factors improved during the first year, whilst anthropometric measures, insulin, HDL- and LDL-cholesterol were also significantly improved after 2 years of treatment. CONCLUSION: Clinically significant weight reductions were achieved after 2 years of VLCD-based treatment. The structure of VLCD treatment during the maintenance phase did not affect weight loss in the total study population, whilst male subjects might benefit from the VLCD on-demand strategy.

A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy womeny.
J Clin Endocrinol Metab. 2003 Apr;88(4):1617-23?
Brehm BJ, Seeley RJ, Daniels SR, D'Alessio DA.?
University of Cincinnati and Children's Hospital Medical Center, Cincinnati, Ohio 45221-0038, USA.

 Untested alternative weight loss diets, such as very low carbohydrate diets, have unsubstantiated efficacy and the potential to adversely affect cardiovascular risk factors. Therefore, we designed a randomized, controlled trial to determine the effects of a very low carbohydrate diet on body composition and cardiovascular risk factors. Subjects were randomized to 6 months of either an ad libitum very low carbohydrate diet or a calorie-restricted diet with 30% of the calories as fat. Anthropometric and metabolic measures were assessed at baseline, 3 months, and 6 months. Fifty-three healthy, obese female volunteers (mean body mass index, 33.6 +/- 0.3 kg/m(2)) were randomized; 42 (79%) completed the trial. Women on both diets reduced calorie consumption by comparable amounts at 3 and 6 months. The very low carbohydrate diet group lost more weight (8.5 +/- 1.0 vs. 3.9 +/- 1.0 kg; P < 0.001) and more body fat (4.8 +/- 0.67 vs. 2.0 +/- 0.75 kg; P < 0.01) than the low fat diet group. Mean levels of blood pressure, lipids, fasting glucose, and insulin were within normal ranges in both groups at baseline. Although all of these parameters improved over the course of the study, there were no differences observed between the two diet groups at 3 or 6 months. beta- Hydroxybutyrate increased significantly in the very low carbohydrate group at 3 months (P = 0.001). Based on these data, a very low carbohydrate diet is more effective than a low fat diet for short-term weight loss and, over 6 months, is not associated with deleterious effects on important cardiovascular risk factors in healthy women.

 

  The beneficial effects of weight loss with a very-low-calorie diet (VLCD) on cardiovascular risk factors have been reported at the end of energy restriction. As the effects, especially on blood pressure, may not remain constant during weight maintenance, we studied the longer-term effects of weight loss on 24h ambulatory blood pressure (ABP), lipids, glucose and insulin. DESIGN: Prospective study of a 17-week weight loss programme containing an eight-week VLCD period and follow-up visit at one-year. SUBJECTS: Twenty-nine moderately obese, normotensive or mildly hypertensive women. The mean +/- s.d. body mass index (BMI) was 36.0 +/- 2.6 kg/m2 and mean age 40.3 +/- 8.3 y. RESULTS: In the last week of the VLCD, the mean (s.d.) weight loss was 12.4 +/- 3.3 kg (P < 0.001), at the end of the programme 15.1 +/- 4.4 kg (P < 0.001 vs baseline), and at one-year follow-up 10.7 +/- 7.6 kg (P < 0.001 vs baseline). Mean 24 h ABP decreased 8.0/4.6 mmHg (P < 0.001 for both) on the last week of the VLCD, at the end of the programme, the systolic ABP decrease was 4.7 mmHg (P < 0.01 vs baseline) and diastolic 2.1 mmHg (not statistically significant (NS) vs baseline). At one-year follow-up, the mean systolic ABP decrease was 4.1 mmHg (P < 0.01 vs baseline) and mean diastolic 3.0 mmHg (P < 0.05 vs baseline). Sodium excretion decreased 55 mmol/24 h in the last VLCD week (P < 0.01) and returned to baseline after that. At the one-year follow-up, beneficial changes, compared with baseline, were observed in mean serum glucose (-0.28 mmol/l, P < 0.05), triglyceride (-0.35 mmol/l, P < 0.01) and HDL cholesterol (+0.16 mmol/l, P < 0.001). CONCLUSIONS: This weight loss programme with a VLCD enabled obese subjects to lose weight and decrease cardiovascular risks. Despite some regain in weight during follow-up, the beneficial effects were overall maintained over the year. Sodium intake tended to increase during follow-up. Information on sodium restriction should be included in weight loss programmes.?