This blog aims to archive articles on alternate day fasting/intermittent fasting in hopes of properly assessing the effectiveness of this eating regimen.
Showing posts with label science. Show all posts
Showing posts with label science. Show all posts

Monday, August 20, 2012

Horizon Eat, Fast and Live Longer

"Michael Mosley has set himself a truly ambitious goal: he wants to live longer, stay younger and lose weight in the bargain. And he wants to make as few changes to his life as possible along the way. He discovers the powerful new science behind the ancient idea of fasting, and he thinks he's found a way of doing it that still allows him to enjoy his food. Michael tests out the science of fasting on himself - with life-changing results."

Eat, Fast and Live Longer - Horizon from Steve Hartman on Vimeo.

Friday, January 22, 2010

Increased p70s6k phosphorylation during intake of a protein–carbohydrate drink following resistance exercise in the fasted state

Deldicque L,De Bock K, Maris M, Ramaekers M,Nielens H, Francaux M, Hespel P (2009) Increased p70s6k phosphorylation during intake of a protein–carbohydrate drink following resistance exercise in the fasted state. European Journal of Applied Physiology
http://www.springerlink.com/content/w8712615714k8150/

Abstract

The present study aimed at comparing the responses of myogenic regulatory factors and signaling pathways involved in muscle protein synthesis after a resistance training session performed in either the fasted or fed state. According to a randomized crossover study design, six young male subjects participated in two experimental sessions separated by 3 weeks. In each session, they performed a standardized resistance training. After the sessions, they received during a 4-h recovery period 6 ml/kg b.w. h of a solution containing carbohydrates (50 g/l), protein hydrolysate (33 g/l), and leucine (16.6 g/l). On one occasion, the resistance exercise session was performed after the intake of a carbohydrate-rich breakfast (B), whereas in the other session they remained fasted (F). Needle biopsies from m. vastus lateralis were obtained before (Rest), and 1 h (+1h) and 4 h (+4h) after exercise. Myogenin, MRF4, and MyoD1 mRNA contents were determined by RT-PCR. Phosphorylation of PKB (protein kinase B), GSK3, p70s6k (p70 ribosomal S6 kinase), eIF2B, eEF2 (eukaryotic elongation factor 2), ERK1/2, and p38 was measured via western blotting. Compared with F, the pre-exercise phosphorylation states of PKB and p70s6k were higher in B, whereas those of eIF2B and eEF2 were lower. During recovery, the phosphorylation state of p70s6k was lower in B than in F (p = 0.02). There were no differences in basal mRNA contents between B and F. However, compared with F at +1h, MyoD1 and MRF4 mRNA contents were lower in B (p < 0.05). Our results indicate that prior fasting may stimulate the intramyocellular anabolic response to ingestion of a carbohydrate/protein/leucine mixture following a heavy resistance training session.

Wednesday, January 20, 2010

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.

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).

Alternate-day fasting in nonobese subjects

Heilbronn LK, Smith SR, Martin CK, Anton SD, Ravussin E. (2005) Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism.Am J Clin Nutr.81(1):69-73
http://www.ajcn.org/cgi/content/full/81/1/69

Abstract
Background: Prolonged dietary restriction increases the life span in rodents. Some evidence suggests that alternate-day fasting may also prolong the life span.

Objective
: Our goal was to determine whether alternate-day fasting is a feasible method of dietary restriction in nonobese humans and whether it improves known biomarkers of longevity.

Design
: Nonobese subjects (8 men and 8 women) fasted every other day for 22 d. Body weight, body composition, resting metabolic rate (RMR), respiratory quotient (RQ), temperature, fasting serum glucose, insulin, free fatty acids, and ghrelin were assessed at baseline and after 21 d (12-h fast) and 22 d (36-h fast) of alternate-day fasting. Visual analogue scales were used to assess hunger weekly.

Results: Subjects lost 2.5 ± 0.5% of their initial body weight (P < 0.001) and 4 ± 1% of their initial fat mass (P < 0.001). Hunger increased on the first day of fasting and remained elevated (P < 0.001). RMR and RQ did not change significantly from baseline to day 21, but RQ decreased on day 22 (P < 0.001), which resulted in an average daily increase in fat oxidation of ≥15 g. Glucose and ghrelin did not change significantly from baseline with alternate-day fasting, whereas fasting insulin decreased 57 ± 4% (P < 0.001).

Conclusions
: Alternate-day fasting was feasible in nonobese subjects, and fat oxidation increased. However, hunger on fasting days did not decrease, perhaps indicating the unlikelihood of continuing this diet for extended periods of time. Adding one small meal on a fasting day may make this approach to dietary restriction more acceptable.

From ScienceNews.org: Possible anticancer power in fasting every other day

originally published January 26th, 2009 on ScienceNews.org
http://www.sciencenews.org/view/generic/id/40242/title/Possible_anticancer_power_in_fasting_every_other_day

Possible anticancer power in fasting every other day
When mice ate as important as what they ate in reducing cell division linked to cancer

Fasting every other day reduces some hallmarks of cancer in mice, even when the mice voraciously consume high-fat food between fasts, a study in an upcoming Nutrition shows.

Scientists have known for decades that eating fewer calories — roughly 25 to 50 percent less than recommended — extends life span in animals ranging from worms to dogs. But, “caloric restriction on a daily basis is very hard,” says Eric Ravussin, a physiologist at the Pennington Biomedical Research Center in Baton Rouge, La., who studies caloric restriction.

Last year, researchers including Krista Varady, then of the University of California, Berkeley, published a study suggesting that a less drastic version of caloric restriction provides a constellation of health benefits in mice. Called alternate-day fasting, the regimen of eating as much food, low-fat in this study, as one wants one day but fasting the next confers some of the same anticancer benefits as just cutting calories at a constant rate, the team found.

But for people, eating a low-fat diet one day and fasting the next is still challenging. Varady and her colleagues wanted to know whether the diet could be made easier to swallow and still provide similar benefits.

In the new study, Varady and other researchers compared mice who fasted every other day, both on high-fat and low-fat diets, to mice that didn’t fast but instead ate a low-fat diet every day. The mice on the ultimate yo-yo diet ate high-fat food, in which 45 percent of the calories came from fat — comparable, Varady says, to human diets of fast food and processed food.

On the fasting days, mice were fed 15 percent of their required calories from either the high- or low-fat food.

The results were surprising, says Varady. Mice that ate the rodent equivalent of Big Macs every other day showed the same anticancer benefits of fasting as the mice that ate the low-fat diet every other day. High rates of cell division — a key feature of cancer — were lower in the mice who fasted every other day than in mice that had not fasted. Mice who fasted every other day also had reduced levels of IGF-1, a protein that induces cell growth and has been linked to cancer.

The new study on mice is the “next installment in a systematic and interesting series of studies” from the researchers, comments James Johnson, a doctor affiliated with the Louisiana State University Health Sciences Center and studies alternate-day fasting in humans.

The option to eat high-fat meals while fasting every other day may make people more likely to stick with the demanding diet regimen, researchers say. To date, only three small studies have examined the effects of alternate-day fasting on people, says Varady, now at the University of Illinois in Chicago.

She says the next step is to see whether an unrestricted high-fat diet one day and a small amount of food the next will confer the same health benefits in humans as it does in mice. Varady and her colleagues are currently conducting a study to test whether humans are able to stick with such a diet. Preliminary data suggest that they can.

“The alternate diet has a lot of potential,” comments Valter Longo, a University of Southern California in Los Angeles researcher who studies aging. But, he adds, “I seriously doubt that very many people would adopt it because it is very tough to do regularly.”

Ravussin knows the difficulty firsthand. When he attempted alternate-day fasting himself, he reported feeling very irritable and hungry. “My wife told me, ‘Don’t do it again.’ ”

Alternate-day fasting and chronic disease prevention: a review of human and animal trials

Varady KA and Hellerstein MK (2007) Alternate-day fasting and chronic disease prevention: a review of human and animal trials. American Journal of Clinical Nutrition, Vol. 86, No. 1, 7-13, July 2007
http://www.ajcn.org/cgi/content/full/86/1/7

Abstract
Calorie restriction (CR) and alternate-day fasting (ADF) represent 2 different forms of dietary restriction. Although the effects of CR on chronic disease prevention were reviewed previously, the effects of ADF on chronic disease risk have yet to be summarized. Accordingly, we review here animal and human evidence concerning ADF and the risk of certain chronic diseases, such as type 2 diabetes, cardiovascular disease, and cancer. We also compare the magnitude of risk reduction resulting from ADF with that resulting from CR. In terms of diabetes risk, animal studies of ADF find lower diabetes incidence and lower fasting glucose and insulin concentrations, effects that are comparable to those of CR. Human trials to date have reported greater insulin-mediated glucose uptake but no effect on fasting glucose or insulin concentrations. In terms of cardiovascular disease risk, animal ADF data show lower total cholesterol and triacylglycerol concentrations, a lower heart rate, improved cardiac response to myocardial infarction, and lower blood pressure. The limited human evidence suggests higher HDL-cholesterol concentrations and lower triacylglycerol concentrations but no effect on blood pressure. In terms of cancer risk, there is no human evidence to date, yet animal studies found decreases in lymphoma incidence, longer survival after tumor inoculation, and lower rates of proliferation of several cell types. The findings in animals suggest that ADF may effectively modulate several risk factors, thereby preventing chronic disease, and that ADF may modulate disease risk to an extent similar to that of CR. More research is required to establish definitively the consequences of ADF.