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[A1CR]

A CRONie noted:

> However, the studies, again, seem to be discussing the peack in diurnal
> bioavailable cortisol, wiht CR; it doesn't seem to address the question of
> total free cortisol for the entire day, as is tested in a 24-hour urine
> test.

The wording of the abstract is ambiguousin THIS study (1): it mentions
the peak value specifically, but also notes that "Although the
FR-dependent enhancement of TOTAL B disappears in aged rats, increased
levels of the bioavailable fraction, free B, appear to be maintained."
That sounds to me like they are, indeed, specifically asserting
increases in absolute free & total corticosterone -- not an increase in
the peak w/ a compensatory suppression elsewhere to yield a net no-sum game.

But in any case: as I previously indicated, (2) was "A longitudinal life
span study of the daily concentration pattern of plasma corticosterone
... in male Fischer 344 rats fed ad libitum or restricted to 60% [al]."
The rodents were tested every 6 mo beginning at 3-4 mo of age, taking
samples every 4h starting at midnight. While the increased peak value is
the most obvious change in CR vs. AL (Fig 2 a-e), the CRONies' B never
drops any LOWER than that of ALers' (Fig 2 a-e), such that the *24h*
plasma free corticosterone concentrations were consistently >= double
ALers at all ages except for an anomaly in the data point for animals
15-19 mo of age (Table 4, and Fig 2C).

Oops: 2 data points. At the last data point, the ALers were all in
terminal disease states (nephropathy & leukemia) "and died shortly after
sampling was completed. Thus, it was deemed inappropriate to report a
mean value for [al] rats in the age range ..." And, of course, 1 day
later, the plasma corticosterone values for CRONies was INFINITELY
greater than that of the dead ALers ...

Likewise, (3) reported that "in food-restricted young rats, the mean
corticosterone level over a 24-h period was significantly elevated above
that in ad libitum fed young rats." They also report that "In aged rats,
however, except before daily feeding, corticosterone levels of
food-restricted rats remained significantly below those of ad libitum
fed animals, whose levels
were, in turn, significantly elevated compared to those of ad libitum
fed young
rats." Per (2), however, this is for TOTAL B, not free; such a finding
would be consistent with (2), which reported that TOTAL B was higher in
young CR vs AL but the same in old, despite the consistent elevation of
FREE B.

Again, (4) found "total circulating corticosterone throughout the day
[measured at "08.00, 11.00, 14.00, 24.00 and 02.00 h "] was higher in
food-restricted than in control rats." These were simply characterized
as "adult" rats, &it was a single event after 34 days' restriction.

-MR

> >1. J Gerontol A Biol Sci Med Sci 2001 Sep;56(9):B391-B397
> > Food restriction enhances endogenous and corticotropin-induced plasma
> > elevations of free but not total corticosterone throughout life in rats.> >
> > Han ES, Evans TR, Shu JH, Lee S, Nelson JF.
> > PMID: 11524440

2. Sabatino F, Masoro EJ, McMahan CA, Kuhn RW.
Assessment of the role of the glucocorticoid system in aging processes
and in
the action of food restriction.
J Gerontol. 1991 Sep;46(5):B171-9.
PMID: 1890278

3. Stewart J, Meaney MJ, Aitken D, Jensen L, Kalant N.
The effects of acute and life-long food restriction on basal and stress-induced
serum corticosterone levels in young and aged rats.
Endocrinology. 1988 Oct;123(4):1934-41.
PMID: 3416820

Armario A, Montero JL, Jolin T.
Chronic food restriction and the circadian rhythms of pituitary-adrenal
hormones, growth hormone and thyroid-stimulating hormone.
Ann Nutr Metab. 1987;31(2):81-7.
PMID: 3035995