Alternate day fasting perils

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Hi All,

Below is a paper that may be of interest in detail.

See the below, which is pdf-available.

The discussion of references 2, 7 and 9 appeared to be of interest.

References 2 and 7 are full-text available.

It was surprising that, in the below contained:

" This was a slight misinterpretation of a study in which we showed that, for

C57BL/6

mice, fasting on alternate days and gorging when food is available mimics

caloric

restriction, without any net reduction in caloric intake.2 C57BL/6 mice were not

selected by chance. We knew at the outset that the same regimen in other strains

was

often not beneficial and could even in some circumstances be fatal.3 "

Anson RM.

Absolute versus relative caloric intake: clues to the mechanism of

calorie/aging-rate interactions.

Ann N Y Acad Sci. 2004 Jun;1019:427-9. Review.

PMID: 15247058

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=15247058

.... In April 2003, many news services (including CNN, CBS, News, and

others)

reported that fasting may be good for one's health. This was a slight

misinterpretation of a study in which we showed that, for C57BL/6 mice, fasting

on

alternate days and gorging when food is available mimics caloric restriction,

without any net reduction in caloric intake.2 C57BL/6 mice were not selected by

chance. We knew at the outset that the same regimen in other strains was often

not

beneficial and could even in some circumstances be fatal.3 The study was

important

not because it showed that an alternate-day fast might promote longevity, but

because it provided a model that can separate a net reduction in caloric intake

from

the protective effects of CR. By comparing mice fed a limited amount of food

daily

(LD) with those subjected to every-other-day (EOD) feeding, one can discern

which

physiological changes are critical for life extension and which are not. Changes

not

shared by both models are, ipso facto, not necessary for the effect.

The initial event that led to that study occurred at a meeting of the

Gerontological

Society of America in the mid-1990s. Ruth Lipman reported the results of a study

(subsequently published4) in which rats were fed a calorically supplemented diet

that included corn oil and sweetened condensed milk. To keep the rats from

becoming

morbidly obese, it was necessary to restrict their access to this food. They

were

limited to an intake that was 8% higher than that of control animals fed the

standard chow. Intriguingly, the speaker noted during the presentation that they

" acted restricted, " eagerly awaiting food and rapidly consuming it when

provided.

If caloric intake could be dissociated from behavior, could it be dissociated

from

aging rate? The thought seemed far-fetched at first, yet a literature search

revealed several studies that suggested that the connection was relative rather

than

absolute. Indeed, one indication that this might be so is the well-established

finding that LD feeding, when begun early in life, lowers body weight. As a

result,

the actual amount of food consumed per gram body weight is often higher in

restricted animals than in ad libitum (AL) controls.5,6

Other lines of evidence also exist. In a dramatic test of the effect of excess

calories on the rate of aging, rats were trained to wade in a room-temperature,

shoulder-high pool for several hours a day. As a result, extra energy was

required

to maintain body temperature. Rats in the experimental group in this study ate,

on

average, 44% more than their dry counterparts. Life span, however, was not

shortened. (Indeed, the trend was in the opposite direction for both average and

maximal life span.)7

Another line of evidence is found in the effects of dietary restriction on ob–/–

mice in comparison with congenic controls. One group reported that ob–/– mice

fed AL

consumed 4.2 g of food per day; AL controls consumed 3.0 g per day. CR mice of

both

genotypes were LD fed at 2.0 g per day. This is equivalent to a 52% restriction

for

the ob–/– mice and to a 33% restriction for the wild-type mice. Despite a high

level

of body fat, the longest-lived mice were in the restricted ob–/– group. While

not

conclusive, the trend supports the thought that it was the relative restriction

level rather than the absolute intake that determined longevity.8

The most direct (but rather obscure) study addressing this issue was published

in

1987.9 In that report, EOD feeding was found to increase life span in C57BL/6J

mice

by 56%, while LD feeding (50% of AL intake) increased it by only 36%. In

contrast,

body weight was decreased by less than 10% in the youngest mice of the EOD

group,

but by nearly 50% in the LD group. In both groups, these numbers decreased with

age.

The topic of the study was body weight and aging interactions, and thus the

question

of food intake was not addressed.

The value of these studies is that they provide us with models that may be used

to

study the mechanism by which caloric intake modulates the aging rate. Holloszy

and

showed that there is an increase in AL intake in response to environmental

conditions that require increased energy expenditure to maintain body

temperature,

without an acceleration in aging rate.7 The effect of CR in combination with

this

treatment is potentially informative. on et al. showed that mice lacking

leptin are extremely responsive to CR.8 Their findings suggest that ob–/– mice

may

even be " restricted " at intake levels that are AL for the ob+/+ mouse. This

model

could be useful in studying many factors that have been proposed to play a

mechanistic role in the calorie/aging-rate interaction. Perhaps the greatest

promise

is offered by comparisons of EOD feeding and LD feeding, two commonly used CR

paradigms. Ingram and Reynolds showed that, in one strain of mice, both

paradigms

result in life extension, despite dramatically different effects on body

weight.9 In

a follow-up to that study, it was demonstrated that the different effects on

body

weight were caused by differences in net caloric intake: in the EOD fed mice,

net

intake approached AL levels.2 Each of these systems offers innumerable

opportunities

for contrast and comparison, and promises to allow us to eliminate variables

that

change coincidentally, not causally, with the alterations in aging rate.

1. McCay, C.M., M.F. Crowell & L.A. Maynard. 1935. The effects of retarded

growth

upon the length of life span and upon the ultimate body size. J. Nutr. 10:

63-79.

2. Anson, R.M. et al. 2003. Intermittent fasting dissociates beneficial effects

of

dietary restriction on glucose metabolism and neuronal resistance to injury from

calorie intake. Proc. Natl. Acad. Sci. USA 100: 6216-6220.

http://www.pnas.org.qe2a-proxy.mun.ca/cgi/content/abstract/100/10/6216?ijkey=bdd\

2d007ee3c2057670f444d79779385f8e0237b & keytype2=tf_ipsecsha

3. Goodrick, C.L. et al. 1990. Effects of intermittent feeding upon body weight

and

lifespan in inbred mice: interaction of genotype and age. Mech. Ageing Dev. 55:

69-87.

4. Lipman, R.D. et al. 1998. Effects of caloric restriction or augmentation in

adult

rats: longevity and lesion biomarkers of aging. Aging (Milano) 10: 463-470.

5. Masoro, E.J., B.P. Yu & H.A. Bertrand. 1982. Action of food restriction in

delaying the aging process. Proc. Natl. Acad. Sci. USA 79: 4239-4241.[Abstract]

6. Hubert, M.F. et al. 2000. The effects of diet, ad libitum feeding, and

moderate

and severe dietary restriction on body weight, survival, clinical pathology

parameters, and cause of death in control Sprague-Dawley rats. Toxicol. Sci. 58:

195-207.

7. Holloszy, J.O. & E.K. . 1986. Longevity of cold-exposed rats: a

reevaluation

of the " rate-of-living theory. " J. Appl. Physiol. 61: 1656-1660.

http://jap.physiology.org.qe2a-proxy.mun.ca/cgi/content/abstract/61/5/1656?ijkey\

=e5a0fe8ac6688f1c6393e53a4cda9178848fabc3 & keytype2=tf_ipsecsha

http://jap.physiology.org.qe2a-proxy.mun.ca/cgi/reprint/61/5/1656?ijkey=e5a0fe8a\

c6688f1c6393e53a4cda9178848fabc3

8. on, D.E., J.R. Archer & C.M. Astle. 1984. Effects of food restriction

on

aging: separation of food intake and adiposity. Proc. Natl. Acad. Sci. USA 81:

1835-1838.

9. Ingram, D.K. & M.A. Reynolds. 1987. The relationship of body weight to

longevity

within laboratory rodent species. In Evolution of Longevity in Animals, pp.

247-282.

Plenum. New York.

Al Pater, PhD; email: old542000@...

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