Re: Fasting/CR, cell growth, insulin-like growth factor-1

[Guest guest]

To me the most notable finding on this paper is that there seems to be a

significant benefit to truly fasting on the " off " day if one is

doing an EOD routine. My primary question is the one that I think isn't

really answered there, although Al poses that question as the opening

line in his post. The 100%-off critters ended up consuming 92.5% of the

food that controls consumed, the 50%-off critters only 97.5%, and the

less-restricted-on-off days probably didn't even do that well. So absent

a fasting-per-se effect, we're talking 7.5% and 2.5% CR, so it isn't

surprising that the 50%-off critters didn't have knock-your-socks-off

results.

More interesting would be a study where the rats weren't able to

compensatorily pig out (rat out) on the " feast " days so that a

greater degree of overall CR was obtained, in my opinion, but clearly one

admonition to take from this report is that to eat wildly after a day of

deprivation won't do you very much good, although a perhaps surprising

amount of good was obtained by the complete-fast-off-day little piggies.

Ratties.

It remains to me an Interesting Question whether days of higher caloric

restriction interspered with less extreme days might yield a useful

long-term strategy to CR.

Maco

At 12:19 PM 5/15/2007, you wrote:

Is it the fasting or the CR that

accounted for the cancer risk benefit for the higher alternate-day

fasting (ADF) regimens? The below paper is pdf-availed. From

Fig. 2 mean grams daily food intake data, the values were 2.95^a for

control ad libitum mice, 3.75^a for the 25% ADF mice, 4.3^b for the 50%

ADF mice and 5.1b for the 100% ADF mice, where different letters are

significantly different, p <0.05. The prostate cells from the

25% ADF mice grew not significantly more than those from ad libitum,

control mice. Ditto for the Fig. 4 25% and 50% insulin-like growth

factor-1 level heights. Therefore, 100% fasts on ADFs appear to be

desirable.

Varady KA, Roohk D, Hellerstein MK.

Dose effects of modified alternate-day fasting regimens on in vivo cell

proliferation and plasma insulin-like growth factor-1 in mice.

J Appl Physiol. 2007 May 10; [Epub ahead of print]

PM! ID: 17495119

Reduced cell proliferation is associated with lower cancer risk.

Alternate-day fasting (ADF), defined as alternating 24 h periods of ad

libitum feeding and fasting, decreases cell proliferation. The effect of

modified regimens of ADF on cell proliferation, however, has not been

examined.

This study measured the effects of modified ADF regimens on prostate and

splenic T-cell proliferation and circulating insulin-like growth factor-1

(IGF-1) levels in mice. In a 4-week study, 24 male C57BL/6J mice were

randomized to 1 of 4 interventions: 1) ADF-25% (25% calorie restriction

[CR] on fast day), 2) ADF-50% (50% CR on fast day), 3) ADF-100% (100% CR

on fast day), and 4) control.

Body weight of the ADF-100% group was less (P < 0.005) than that of

the ADF-25% and ADF-50% groups post-treatment. On the feast day, the

ADF-100% and ADF-50% groups ate 85% and 45% more food, respectively, than

controls, indicating a hyperphagic response to fasting. Proliferation

rates of T-cells were 6% and 30% lower (P < 0.05) in the ADF-50% and

ADF-100% groups, respectively, relative to controls. Prostate cell

proliferation was reduced (P < 0.05) by 49% in the ADF-100% group,

relative to controls, but did not change in the other groups. IGF-1

levels were reduced (P < 0.05) by 40%, relative to controls, in the

ADF-100% group.

These findings confirm the beneficial effects of ADF-100% on cancer risk,

by decreasing cell proliferation and IGF-1 levels, and suggest that

modified ADF regimens comprising 25-50% CR on the fast day do not

replicate these effects.

.... Seven-week old C57BL/6J male mice ... At 8 weeks of age, the mice

were randomized to 1 of 4 intervention groups (n = 6 per group). The

firstintervention group (ADF-25%) was fed the semi-purified AIN-93M diet

ad libitum on the feast day, and a25% calorie-restricted diet on

alternate days (fast day). The second group (ADF-50%) was fed the AIN-93M

diet ad libitum on the feast day, and a 50% calorie-restricted diet on

the fast day. The third group (ADF-100%) was fed the AIN-93M diet ad

libitum on the feast day, and underwent a complete fast on alternate

days. The fourth group acted as the control, and was fed the AIN-93M diet

ad libitum each day. Food was provided or taken away at 13.00 h each day.

....

.... in Figure 1. All groups weighed approximately the same during

acclimation, and all gained weight at the same rate during weeks 1 and 2.

By week 3, however, the ADF-100% group did not continue to gain weight at

the same rate as the other groups, and by week 4, the ADF-100% group

weighed significantly less (P < 0.05) than the ADF-50% group. By the

end of the study, the ADF-100% group weighed less (P < 0.005) than

both the ADF-25% and ADF-50% groups. Overall, all groups gained weight (P

< 0.05) from the beginning to the end of the study.

Food intake

During acclimation, all mice consumed, on average, approximately 3.5 g/d

of food. The ADF-100% group ate ~11% less (P < 0.001) and ~16% less (P

< 0.0001) than the other treatment groups during weeks 1 and 2,

respectively, indicating an acute inability of the ADF-100% group to

compensate fully on the feast day for the lack of food consumption on the

fast day. Mean weekly food intake of the ADF-100% group increased during

week 3 and no significant differences were observed between groups.

During week 4, however, the amount of food consumed by the ADF-100% group

fell to ~25% less (P < 0.001) than that of the other treatment

groups.

Hyperphagic response to food restriction

A hyperphagic response on the feast day to food restriction on the fast

day (P < 0.05) was noted in each of the ADF intervention groups at

week 1 (Figure 2). During week 1, the mean daily food intake on the feast

day was 3.4 g/d, 3.9 g/d, 4.7 g/d in the ADF-25%, ADF-50% and ADF-100%

groups, respectively. The hyperphagic response persisted throughout the

study, as the ADF-50% and ADF-100% groups consumed ~45% and ~85% more (P

< 0.05) food, respectively, on feast days than the control group. This

hyperphagic response, however, did not persist after the first week in

the ADF-25% group.

In vivo splenic T-cell and prostate 175 cell proliferation

Splenic T-cell and prostate cell proliferation rates after 4 weeks of ADF

are shown in Figure 3. At the end of the study, splenic T-cell

proliferation was 6% and 29% lower (P < 0.05 for each) in the ADF-50%

and ADF-100% groups, respectively, relative to controls. Prostate cell

proliferation was 49% lower (P < 0.05) in the ADF-100% group compared

to controls. Thus, restricting food completely on the fast day resulted

in significant reductions in proliferation of both cell types.

Restricting food by 50% on the fast day reduced splenic T-cell

proliferation modestly.

Insulin like growth factor-1

Circulating IGF-1 levels are shown in Figure 4. Plasma IGF-1

concentrations were markedly reduced (P < 0.01) in the ADF-100% group

when compared to all other groups. Relative to controls, IGF-1 levels

were 40% lower in the ADF-100% group. IGF-1 concentrations were not

significantly different in the ADF-25% or ADF-50% groups compared to

controls. Plasma IGF-1 levels exhibited positive, though only moderate,

correlations with in vivo proliferation rates of both splenic T-cell (r =

0.48, P = 0.02) and prostate cells (r = 0.43, P = 0.04).

.... In summary, these findings suggest that true ADF-100% results in

reductions in cell proliferation rates and plasma IGF-1 levels, but that

modified regimens of ADF (e.g., 25-50% reductions in food intake on the

fast days) do not. The ability of ADF to decrease these cancer risk

parameters was shown to be both potent and rapid, as reductions were

shown after only 4 weeks of diet. ...

-- Al Pater,

alpater@...

Bored

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[Guest guest]

Hi folks:

Am I reading this right? If not please correct me.

It seems to me that the ADF 100% mice in this experiment were

consuming 7.5% less food per week than the controls and, for a

number, saw a 29% reduction in splenic T-cell proliferation; a 49%

reduction in prostate cell proliferation; and 40% reduction in IGF-1.

Now here seems (to me) to be the relevant question:

" Would you expect reductions of similar magnitude in response to a

mere 7.5% straight CRON? "

My guess is that in response to such a small degree of CRON one

wouldn't expect to see benefits anywhere near as large.

So, tentatively, it looks to me as if this paper may be suggesting

that CRON administered in an ADF 100% format ***MAY*** be better than

CRON eating the same amount daily.

Of course this particular study doesn't tell us anything specifically

about larger degrees of CRON - say 30% for example. And it is more

than possible that, as with other treatments, 40% CRON may already

fix any benefit that can be provided by alternative treatments.

But on the face of it, it looks like ADF 100%, with only 7.5%

restriction, may be at least as good for cancer prevention as 30%

CRON?

(Or perhaps I am confused? lol)

What do you guys think?

Rodney.

>

> Is it the fasting or the CR that accounted for the cancer risk

benefit for the higher alternate-day fasting (ADF) regimens? The

below paper is pdf-availed. From Fig. 2 mean grams daily food intake

data, the values were 2.95^a for control ad libitum mice, 3.75^a for

the 25% ADF mice, 4.3^b for the 50% ADF mice and 5.1b for the 100%

ADF mice, where different letters are significantly different, p

<0.05. The prostate cells from the 25% ADF mice grew not

significantly more than those from ad libitum, control mice. Ditto

for the Fig. 4 25% and 50% insulin-like growth factor-1 level

heights. Therefore, 100% fasts on ADFs appear to be desirable.

>

>

> Varady KA, Roohk D, Hellerstein MK.

> Dose effects of modified alternate-day fasting regimens on in vivo

cell proliferation and plasma insulin-like growth factor-1 in mice.

> J Appl Physiol. 2007 May 10; [Epub ahead of print]

> PMID: 17495119

>

> Reduced cell proliferation is associated with lower cancer risk.

Alternate-day fasting (ADF), defined as alternating 24 h periods of

ad libitum feeding and fasting, decreases cell proliferation. The

effect of modified regimens of ADF on cell proliferation, however,

has not been examined.

>

> This study measured the effects of modified ADF regimens on

prostate and splenic T-cell proliferation and circulating insulin-

like growth factor-1 (IGF-1) levels in mice. In a 4-week study, 24

male C57BL/6J mice were randomized to 1 of 4 interventions: 1) ADF-

25% (25% calorie restriction [CR] on fast day), 2) ADF-50% (50% CR on

fast day), 3) ADF-100% (100% CR on fast day), and 4) control.

>

> Body weight of the ADF-100% group was less (P < 0.005) than that

of the ADF-25% and ADF-50% groups post-treatment. On the feast day,

the ADF-100% and ADF-50% groups ate 85% and 45% more food,

respectively, than controls, indicating a hyperphagic response to

fasting. Proliferation rates of T-cells were 6% and 30% lower (P <

0.05) in the ADF-50% and ADF-100% groups, respectively, relative to

controls. Prostate cell proliferation was reduced (P < 0.05) by 49%

in the ADF-100% group, relative to controls, but did not change in

the other groups. IGF-1 levels were reduced (P < 0.05) by 40%,

relative to controls, in the ADF-100% group.

>

> These findings confirm the beneficial effects of ADF-100% on

cancer risk, by decreasing cell proliferation and IGF-1 levels, and

suggest that modified ADF regimens comprising 25-50% CR on the fast

day do not replicate these effects.

>

> ... Seven-week old C57BL/6J male mice ... At 8 weeks of age, the

mice were randomized to 1 of 4 intervention groups (n = 6 per group).

The firstintervention group (ADF-25%) was fed the semi-purified AIN-

93M diet ad libitum on the feast day, and a25% calorie-restricted

diet on alternate days (fast day). The second group (ADF-50%) was fed

the AIN-93M diet ad libitum on the feast day, and a 50% calorie-

restricted diet on the fast day. The third group (ADF-100%) was fed

the AIN-93M diet ad libitum on the feast day, and underwent a

complete fast on alternate days. The fourth group acted as the

control, and was fed the AIN-93M diet ad libitum each day. Food was

provided or taken away at 13.00 h each day. ...

>

> ... in Figure 1. All groups weighed approximately the same during

acclimation, and all gained weight at the same rate during weeks 1

and 2. By week 3, however, the ADF-100% group did not continue to

gain weight at the same rate as the other groups, and by week 4, the

ADF-100% group weighed significantly less (P < 0.05) than the ADF-50%

group. By the end of the study, the ADF-100% group weighed less (P <

0.005) than both the ADF-25% and ADF-50% groups. Overall, all groups

gained weight (P < 0.05) from the beginning to the end of the study.

>

> Food intake

>

> During acclimation, all mice consumed, on average, approximately

3.5 g/d of food. The ADF-100% group ate ~11% less (P < 0.001) and

~16% less (P < 0.0001) than the other treatment groups during weeks 1

and 2, respectively, indicating an acute inability of the ADF-100%

group to compensate fully on the feast day for the lack of food

consumption on the fast day. Mean weekly food intake of the ADF-100%

group increased during week 3 and no significant differences were

observed between groups. During week 4, however, the amount of food

consumed by the ADF-100% group fell to ~25% less (P < 0.001) than

that of the other treatment groups.

>

> Hyperphagic response to food restriction

>

> A hyperphagic response on the feast day to food restriction on

the fast day (P < 0.05) was noted in each of the ADF intervention

groups at week 1 (Figure 2). During week 1, the mean daily food

intake on the feast day was 3.4 g/d, 3.9 g/d, 4.7 g/d in the ADF-25%,

ADF-50% and ADF-100% groups, respectively. The hyperphagic response

persisted throughout the study, as the ADF-50% and ADF-100% groups

consumed ~45% and ~85% more (P < 0.05) food, respectively, on feast

days than the control group. This hyperphagic response, however, did

not persist after the first week in the ADF-25% group.

>

> In vivo splenic T-cell and prostate 175 cell proliferation

>

> Splenic T-cell and prostate cell proliferation rates after 4

weeks of ADF are shown in Figure 3. At the end of the study, splenic

T-cell proliferation was 6% and 29% lower (P < 0.05 for each) in the

ADF-50% and ADF-100% groups, respectively, relative to controls.

Prostate cell proliferation was 49% lower (P < 0.05) in the ADF-100%

group compared to controls. Thus, restricting food completely on the

fast day resulted in significant reductions in proliferation of both

cell types. Restricting food by 50% on the fast day reduced splenic T-

cell proliferation modestly.

>

> Insulin like growth factor-1

>

> Circulating IGF-1 levels are shown in Figure 4. Plasma IGF-1

concentrations were markedly reduced (P < 0.01) in the ADF-100% group

when compared to all other groups. Relative to controls, IGF-1 levels

were 40% lower in the ADF-100% group. IGF-1 concentrations were not

significantly different in the ADF-25% or ADF-50% groups compared to

controls. Plasma IGF-1 levels exhibited positive, though only

moderate, correlations with in vivo proliferation rates of both

splenic T-cell (r = 0.48, P = 0.02) and prostate cells (r = 0.43, P =

0.04).

>

> ... In summary, these findings suggest that true ADF-100% results

in reductions in cell proliferation rates and plasma IGF-1 levels,

but that modified regimens of ADF (e.g., 25-50% reductions in food

intake on the fast days) do not. The ability of ADF to decrease these

cancer risk parameters was shown to be both potent and rapid, as

reductions were shown after only 4 weeks of diet. ...

>

> -- Al Pater, alpater@...

>

>

> ---------------------------------

> Bored stiff? Loosen up...

> Download and play hundreds of games for free on Games.

>

[Guest guest]

Rodney,

The 100% ADF regimen exhausts the body's carbohydrate (glycogen)

reserves and forces the body to burn fat on the fasting days. Plain

CR never quite gets to this stage since the meals are administered at

more closely spaced intervals. Something that happens on the

fat-burning days could account for the difference.

Tony

> >

> > Is it the fasting or the CR that accounted for the cancer risk

> benefit for the higher alternate-day fasting (ADF) regimens? The

> below paper is pdf-availed. From Fig. 2 mean grams daily food intake

> data, the values were 2.95^a for control ad libitum mice, 3.75^a for

> the 25% ADF mice, 4.3^b for the 50% ADF mice and 5.1b for the 100%

> ADF mice, where different letters are significantly different, p

> <0.05. The prostate cells from the 25% ADF mice grew not

> significantly more than those from ad libitum, control mice. Ditto

> for the Fig. 4 25% and 50% insulin-like growth factor-1 level

> heights. Therefore, 100% fasts on ADFs appear to be desirable.

> >

> >

> > Varady KA, Roohk D, Hellerstein MK.

> > Dose effects of modified alternate-day fasting regimens on in vivo

> cell proliferation and plasma insulin-like growth factor-1 in mice.

> > J Appl Physiol. 2007 May 10; [Epub ahead of print]

> > PMID: 17495119

> >

> > Reduced cell proliferation is associated with lower cancer risk.

> Alternate-day fasting (ADF), defined as alternating 24 h periods of

> ad libitum feeding and fasting, decreases cell proliferation. The

> effect of modified regimens of ADF on cell proliferation, however,

> has not been examined.

> >

> > This study measured the effects of modified ADF regimens on

> prostate and splenic T-cell proliferation and circulating insulin-

> like growth factor-1 (IGF-1) levels in mice. In a 4-week study, 24

> male C57BL/6J mice were randomized to 1 of 4 interventions: 1) ADF-

> 25% (25% calorie restriction [CR] on fast day), 2) ADF-50% (50% CR on

> fast day), 3) ADF-100% (100% CR on fast day), and 4) control.

> >

> > Body weight of the ADF-100% group was less (P < 0.005) than that

> of the ADF-25% and ADF-50% groups post-treatment. On the feast day,

> the ADF-100% and ADF-50% groups ate 85% and 45% more food,

> respectively, than controls, indicating a hyperphagic response to

> fasting. Proliferation rates of T-cells were 6% and 30% lower (P <

> 0.05) in the ADF-50% and ADF-100% groups, respectively, relative to

> controls. Prostate cell proliferation was reduced (P < 0.05) by 49%

> in the ADF-100% group, relative to controls, but did not change in

> the other groups. IGF-1 levels were reduced (P < 0.05) by 40%,

> relative to controls, in the ADF-100% group.

> >

> > These findings confirm the beneficial effects of ADF-100% on

> cancer risk, by decreasing cell proliferation and IGF-1 levels, and

> suggest that modified ADF regimens comprising 25-50% CR on the fast

> day do not replicate these effects.

> >

> > ... Seven-week old C57BL/6J male mice ... At 8 weeks of age, the

> mice were randomized to 1 of 4 intervention groups (n = 6 per group).

> The firstintervention group (ADF-25%) was fed the semi-purified AIN-

> 93M diet ad libitum on the feast day, and a25% calorie-restricted

> diet on alternate days (fast day). The second group (ADF-50%) was fed

> the AIN-93M diet ad libitum on the feast day, and a 50% calorie-

> restricted diet on the fast day. The third group (ADF-100%) was fed

> the AIN-93M diet ad libitum on the feast day, and underwent a

> complete fast on alternate days. The fourth group acted as the

> control, and was fed the AIN-93M diet ad libitum each day. Food was

> provided or taken away at 13.00 h each day. ...

> >

> > ... in Figure 1. All groups weighed approximately the same during

> acclimation, and all gained weight at the same rate during weeks 1

> and 2. By week 3, however, the ADF-100% group did not continue to

> gain weight at the same rate as the other groups, and by week 4, the

> ADF-100% group weighed significantly less (P < 0.05) than the ADF-50%

> group. By the end of the study, the ADF-100% group weighed less (P <

> 0.005) than both the ADF-25% and ADF-50% groups. Overall, all groups

> gained weight (P < 0.05) from the beginning to the end of the study.

> >

> > Food intake

> >

> > During acclimation, all mice consumed, on average, approximately

> 3.5 g/d of food. The ADF-100% group ate ~11% less (P < 0.001) and

> ~16% less (P < 0.0001) than the other treatment groups during weeks 1

> and 2, respectively, indicating an acute inability of the ADF-100%

> group to compensate fully on the feast day for the lack of food

> consumption on the fast day. Mean weekly food intake of the ADF-100%

> group increased during week 3 and no significant differences were

> observed between groups. During week 4, however, the amount of food

> consumed by the ADF-100% group fell to ~25% less (P < 0.001) than

> that of the other treatment groups.

> >

> > Hyperphagic response to food restriction

> >

> > A hyperphagic response on the feast day to food restriction on

> the fast day (P < 0.05) was noted in each of the ADF intervention

> groups at week 1 (Figure 2). During week 1, the mean daily food

> intake on the feast day was 3.4 g/d, 3.9 g/d, 4.7 g/d in the ADF-25%,

> ADF-50% and ADF-100% groups, respectively. The hyperphagic response

> persisted throughout the study, as the ADF-50% and ADF-100% groups

> consumed ~45% and ~85% more (P < 0.05) food, respectively, on feast

> days than the control group. This hyperphagic response, however, did

> not persist after the first week in the ADF-25% group.

> >

> > In vivo splenic T-cell and prostate 175 cell proliferation

> >

> > Splenic T-cell and prostate cell proliferation rates after 4

> weeks of ADF are shown in Figure 3. At the end of the study, splenic

> T-cell proliferation was 6% and 29% lower (P < 0.05 for each) in the

> ADF-50% and ADF-100% groups, respectively, relative to controls.

> Prostate cell proliferation was 49% lower (P < 0.05) in the ADF-100%

> group compared to controls. Thus, restricting food completely on the

> fast day resulted in significant reductions in proliferation of both

> cell types. Restricting food by 50% on the fast day reduced splenic T-

> cell proliferation modestly.

> >

> > Insulin like growth factor-1

> >

> > Circulating IGF-1 levels are shown in Figure 4. Plasma IGF-1

> concentrations were markedly reduced (P < 0.01) in the ADF-100% group

> when compared to all other groups. Relative to controls, IGF-1 levels

> were 40% lower in the ADF-100% group. IGF-1 concentrations were not

> significantly different in the ADF-25% or ADF-50% groups compared to

> controls. Plasma IGF-1 levels exhibited positive, though only

> moderate, correlations with in vivo proliferation rates of both

> splenic T-cell (r = 0.48, P = 0.02) and prostate cells (r = 0.43, P =

> 0.04).

> >

> > ... In summary, these findings suggest that true ADF-100% results

> in reductions in cell proliferation rates and plasma IGF-1 levels,

> but that modified regimens of ADF (e.g., 25-50% reductions in food

> intake on the fast days) do not. The ability of ADF to decrease these

> cancer risk parameters was shown to be both potent and rapid, as

> reductions were shown after only 4 weeks of diet. ...

> >

> > -- Al Pater, alpater@

> >

> >

> > ---------------------------------

> > Bored stiff? Loosen up...

> > Download and play hundreds of games for free on Games.

> >

>