from fitnessspotlight.com: Benefits of Intermittent fasting

A good article on living the ADF life from fitnessspotlight.com
http://www.fitnessspotlight.com/2010/01/13/benefits-intermittent-fasting/

some highlights:
benefits of IF (ADF):

• Reduced blood glucose and insulin levels (markers of improved health)
• Increased fatty acid oxidation
• Maintenance of lean mass (muscle)
• Reduced inflammation
• Reduced oxidative damage
• Increased cellular stress resistance (esp of heart and brain)
• Decreased risks associated with degenerative diseases of aging (cancers, heart diseases, diabetes, Alzheimers)

Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems.

Mattson MP, Wan R (2005) Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. J Nutr Biochem. 16(3):129-37.

Abstract
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.

Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction

Varady KA, Allister CA, Roohk DJ, Hellerstein MK (2009) Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction.J Nutr Biochem. Epub

Abstract
Calorie restriction (CR) and alternate-day fasting (ADF) beneficially affect several aspects of adipose tissue physiology, but direct comparisons between regimens have yet to be performed. The present study evaluated the effects of ADF versus CR on body fat distribution and circulating adiponectin levels and examined the kinetic mechanisms that underlie changes in fat distribution. Thirty female C57BL/6J mice were randomized to one of five groups for 4 weeks: (a) CR-25% (25% energy restriction daily), (b) ADF-75% (75% restriction on fast day), (c) ADF-85% (85% restriction on fast day), (d) ADF-100% (100% restriction on fast day) and (e) control (ad libitum fed). Body weights of the CR mice were lower than that of the ADF and control groups posttreatment. After 4 weeks of diet, the proportion of visceral fat decreased (P<.001) and the proportion of subcutaneous fat increased (P<.001) similarly in ADF and CR animals. Adiponectin increased (P<.05) by 62-86% in the ADF groups and by 69% in the CR group. Triglyceride (TG) synthesis and de novo lipogenesis were augmented (P<.05) in the subcutaneous fat pad of ADF and CR animals, relative to control. No differences in net lipolysis were observed, resulting in greater TG accumulation in the subcutaneous fat pad, with a shift in the ratio of TG between depots. These findings indicate that ADF (both modified and true) produces similar beneficial modulations in body fat distribution and adiponectin levels as daily CR

Modified alternate-day fasting regimens reduce cell proliferation rates to a similar extent as daily calorie restriction in mice

Varady KA, Roohk DJ, McEvoy-Hein BK, Gaylinn BD, Thorner MO, Hellerstein MK (2008) Modified alternate-day fasting regimens reduce cell proliferation rates to a similar extent as daily calorie restriction in mice. FASEB J.(6):2090-6

Abstract
Calorie restriction (CR) and alternate-day fasting (ADF) reduce cancer risk and reduce cell proliferation rates. Whether modified ADF regimens (i.e., allowing a portion of energy needs to be consumed on the fast day) work, as well as true ADF or CR to reduce global cell proliferation rates, remains unresolved. Here, we measured the effects of true ADF, modified ADF, and daily CR on cell proliferation rates in mice. Thirty female C57BL/6J mice were randomized to one of five interventions for 4 wk: 1) CR-25% (25% reduction in daily energy intake), 2) ADF-75% (75% reduction on fast day), 3) ADF-85% (85% reduction on fast day), 4) ADF-100% (100% reduction on fast day), and 5) control (ad libitum intake). Body weights of the ADF groups did not differ from controls, whereas the CR-25% group weighed less than all other groups posttreatment. Epidermal cell proliferation decreased (P<0.01) by 29, 20, and 31% in the CR-25%, ADF-85% and ADF-100% groups, respectively, relative to controls. Proliferation rates of splenic T cells were reduced (P<0.01) by 37, 32, and 31% in the CR-25%, ADF-85%, and ADF-100% groups, respectively, and mammary epithelial cell proliferation was 70, 65, and 62% lower (P<0.01), compared with controls. Insulin-like growth factor-1 levels were reduced (P<0.05) in the CR-25% and ADF-100% groups only. In summary, modified ADF, allowing the consumption of 15% of energy needs on the restricted intake day, decreases global cell proliferation similarly as true ADF and daily CR without reducing body weight.

Life extension by calorie restriction in humans

Everitt AV, Le Couteur DG (2007) Life extension by calorie restriction in humans Ann N Y Acad Sci. 1114:428-33

Abstract
Long-term reduction in energy intake in the diet (calorie restriction [CR]) extends the life of the laboratory rat by about 25%. However, in humans there are no life-long studies of CR, but only short-term trials which indicate that 20% CR acting over periods of 2-6 years is associated with reduced body weight, blood pressure, blood cholesterol, and blood glucose--risk factors for the major killer diseases of cardiovascular disease and diabetes. In addition, recent research has shown that CR for 6 months is able to improve biomarkers for longevity (deep body temperature and plasma insulin) and thus should increase life expectancy. The magnitude of the life-extension effect of CR in humans can only be estimated. The Okinawans, the longest-lived people on earth, consume 40% fewer calories than the Americans and live only 4 years longer. Similarly, women in United States consume 25% fewer calories than men and live 5 years longer. From the survival studies of overweight and obese people, it is estimated that long-term CR to prevent excessive weight gain could add only 3-13 years to life expectancy. Thus the effects of CR on human life extension are probably much smaller than those achieved by medical and public health interventions, which have extended life by about 30 years in developed countries in the 20th century, by greatly reducing deaths from infections, accidents, and cardiovascular disease

Effects of modified alternate-day fasting regimens on adipocyte size, triglyceride metabolism, and plasma adiponectin levels in mice

Varady KA, Roohk DJ, Loe YC, McEvoy-Hein BK, Hellerstein MK (2007) Effects of modified alternate-day fasting regimens on adipocyte size, triglyceride metabolism, and plasma adiponectin levels in mice. J Lipids Res 48(10):2212-9

Calorie restriction (CR) affects adipocyte function and reduces body weight. However, the effects of alternate-day fasting (ADF) on adipose biology remain unclear. This study examined the effects of ADF and modified ADF regimens on adipocyte size, triglyceride (TG) metabolism, and adiponectin levels in relation to changes in body weight and adipose mass. Twenty-four male C57BL/6J mice were randomized for 4 weeks among 1) ADF-25% (25% CR on fast day, ad libitum on alternate day), 2) ADF-50% (50% CR on fast day), 3) ADF-100% (100% CR on fast day), and 4) control (ad libitum). The body weight of ADF-100% mice was lower than that of the other groups (P < 0.005) after treatment. Adipose tissue weights did not change. Inguinal and epididymal fat cells were 35-50% smaller (P < 0.01) than those of controls in ADF-50% and ADF-100% animals after treatment. Net lipolysis was augmented (P < 0.05) in ADF-100% mice, and the contribution from glyceroneogenesis to alpha-glycerol phosphate increased in ADF-50% and ADF-100% mice, whereas fractional and absolute de novo lipogenesis also increased in ADF-50% and ADF-100% animals, consistent with an alternating feast-fast milieu. Plasma adiponectin levels were not affected. In summary, modified ADF (ADF-50%) and complete ADF (ADF-100%) regimens modulate adipocyte function, despite there being no change in body weight or adipose tissue weight in the former group.

Alternate-day fasting reduces global cell proliferation rates independently of dietary fat content in mice

Varady KA, Roohk DJ, Bruss M, Hellerstein MK (2009) Alternate-day fasting reduces global cell proliferation rates independently of dietary fat content in mice. Nutrition. 25(4):486-9

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.

hypothesis: Pretreatment with alternate day modified fast will permit higher dose and frequency of cancer chemotherapy and better cure rates

Please note: This is a medical hypothesis and is currently not backed up by data from a clinical trial

Johnson JB, John S, Laub DR (2009) Pretreatment with alternate day modified fast will permit higher dose and frequency of cancer chemotherapy and better cure rates. Med Hypotheses.72(4):381-2

Abstract
It is established that calorie restriction (CR) increases the resistance of cells to various stressors such as oxidative damage, excitotoxins, mercury and acetaminophen. Alternate day feeding (ADF) may confer greater stress resistance than daily CR of 30% or 40%. A recent study in three strains of mouse showed that a fast of 48 or 60 h prevented toxic effects due to administration of doses 2-4 times the maximum human dose of etoposide, a chemotherapy agent which acts through increased oxidative stress. In addition, mice inoculated with neuroblastoma survived longer when pretreated with fasting, then given high dose etoposide, as well as not exhibiting toxicity. This increased survival was construed as evidence of differential stress resistance between normal and cancer cells, the cancer cells being only partially protected by the pretreatment fast. In clinical practice, increased differential stress resistance could lead to the use of much higher doses of chemotherapy agents, and in the absence of toxicity, make it possible to repeat the treatment to kill residual cancer cells. Humans are unlikely to comply with a total fast of longer than 24 or 48 h, which may be insufficient to activate the same gene expression process. Based on published data we estimate that an optimal time period for development of stress resistance is 2-3 weeks when alternate day feeding is employed. Our previously published experience suggests that 2-3 weeks of alternate day modified fast in which subjects eat ad libitum one day and <20% of one's estimated caloric requirement the next will confer a similar stress resistance. Compliance with this diet is high and greater maintenance of body weight is feasible. We hypothesize that a pretreatment of 2-3 weeks with the alternate day modified fast will improve outcomes in cancer chemotherapy, decreasing morbidity and raising cure rates.

Modified alternate-day fasting and cardioprotection

Varady KA, Hudak CS, Hellerstein MK. (2009) Modified alternate-day fasting and cardioprotection: relation to adipose tissue dynamics and dietary fat intake. Metabolism. 58(6):803-11.

Abstract
The relation between alternate-day fasting (ADF) and cardioprotection remains uncertain. In the present study, we examined the ability of modified ADF, with a low-fat (LF) vs high-fat (HF) background diet, to modulate adipose tissue physiology in a way that may protect against coronary heart disease. In a 4-week study, male C57BL/6 mice were randomized to 1 of 3 groups: (1) ADF-85%-LF (85% energy restriction on fast day, ad libitum fed on feed day, on an LF diet), (2) ADF-85%-HF (same protocol but HF diet), and (3) control (ad libitum fed). Throughout the study, body weight did not differ between ADF and control animals. Proportion of subcutaneous fat increased (P < .01), whereas the proportion of visceral fat decreased (P < .01), in both ADF groups. Triglyceride (TG) synthesis was augmented (P < .05) in subcutaneous fat, but remained unchanged in visceral fat. Adiponectin concentrations were elevated (P < .05), whereas leptin and resistin levels decreased (P < .05). Aortic vascular smooth muscle cell proliferation was reduced (P < .05) by 60% and 76% on the LF and HF diets, respectively. Plasma total cholesterol, TG, and free fatty acid concentrations also decreased (P < .05). In summary, modified ADF regimens alter adipose tissue physiology (ie, body fat distribution, TG metabolism, and adipokines) in a way that may protect against coronary heart disease. These beneficial effects were noted over a wide range of fat intake, suggesting that ADF may be protective even in the presence of HF diets.

Caloric restriction delays disease onset and mortality in rhesus monkeys

Please note: the owner of this blog does not support any scientific experimentation on primates (and in general is against the use of animals in biomedical experimentation). Nevertheless, I am posting this work out of respect for the monkeys who are living in biomedical research facilities and giving their lives unwillingly to science. This is perhaps a perfect example of how this research would have been more effective and conclusive had it been done in humans.

Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R. (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009 Jul 10;325(5937):201-4.

Abstract
Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established. We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research. In a population of rhesus macaques maintained at the Wisconsin National Primate Research Center, moderate CR lowered the incidence of aging-related deaths. At the time point reported, 50% of control fed animals survived as compared with 80% of the CR animals. Furthermore, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy. These data demonstrate that CR slows aging in a primate species.

On the left is Canto (27) and on the right is Owen (29). Canto is fed with about 30% less calories than Owen (CR).