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Mark Rosenzweig · Guest

On Jun 27, 9:04 pm, "Andrew B. Chung, MD/PhD" <lo...@thetruth.com>
wrote:
[quote]neighbor Keith Hopkins wrote:
satan via a sockpuppet (corporeal demon) despairingly posted:
Andrew, in the Holy Spirit, boldly wrote:

http://groups.google.com/group/sci.med.cardiology/msg/ee5bb1d65b2be594?

Dear Doctor Chunghole,

Your followers have been sitting up at night waiting to find out if
you have found a cure for the son of your rash- you know, the one
that>s just a bit too far out of reach, but the one that all of us
followers reach out to in hunger and health and call our messiah
Jesus
Rash? Or would you perhaps rather move your rash>s sabbath to
Wednesday soas to draw more attention to the raging red cluster of
itchy skin that we all pray to?

That was a bit rash, don>t you think?

(I>m so sorry.)

(You can be forgiven by simply trusting Jesus :-)

It remains wiser to simply rebuke satan and move on to addressing the
others:

http://groups.google.com/group/sci.med.cardiology/msg/31c3b88286afc5bd?

May you and other dear neighbors, friends, and brethren have a
blessedly wonderful 2008th year since the birth of our LORD Jesus
Christ as our Messiah, the Son of Man ...

... by being hungrier:

http://groups.google.com/group/sci.med.cardiology/msg/f891e617d10bd689?

Hunger is wonderful ! ! !

It>s how we know what GOD desires, which is all that is good.

Yes, hunger is our knowledge of good versus evil that Adam and Eve
paid for with their and our immortal lives.

"Blessed are you who hunger NOW...

... for you will be satisfied." -- LORD Jesus Christ (Luke 6:21)

Amen.

Here is a Spirit-guided exegesis of Luke 6:21 given in hopes of
promoting much greater understanding:

http://groups.google.com/group/sci.med.cardiology/msg/cc2aa8f8a4d41360?

Be hungry... be healthy... be hungrier... be healthier...

Marana tha

Prayerfully in the awesome name of our Messiah, Jesus Christ,

Andrew
--http://groups.google.com/group/sci.med.cardiology/msg/4128be9f9918d825?- Hide quoted text -

- Show quoted text -
[/quote]
http://www.youtube.com/watch?v=MeSSwKffj9o

jc101 · Guest

On Jun 27, 11:19 am, fr.r...@free.fr wrote:
[quote]I definitely adopt this name: too cool "Faith Based Moderate Caloric
Restrictionnists' !!!
In fact since a double blind placebo controlled study regarding CR
with humans is totally
impossible, the only actual solution is to believe that results from
animals can extend to
humans; the future will tell us if this faith was right.

By the way, the full text from this study is very interesting and ask
a lot of questions

François Rose
[/quote]
I am glad that this descriptive title FBMCR - Faith Based Moderate
Calorie Restriction is appealing.

Since the rodent data clearly shows that effective CR (40% less -
daily 1500 calories in man) started in mid aged mice shortens
lifespan : "The shift from AL-->CR increased mortality in 17- and 24-
month-old mice..." it definitely requires a "leap of faith" to think
that effective CR will increase lifespan used in middle aged or
elderly adults, suggesting characteristics of religion. This "moderate
CR" is a fine "religion of deprivation" for those for whom it is
psychologically important.

As long as these "moderate CR" adults don>t move into "effective
CR" (which is 40% off calories, BMI 18.5 or below) they will probably
not shorten lifespan too much, as occurred in this study. I suspect
that the means by which effective CR shortens lifespan initiated in
adults is by causing low IGF-1 and other growth factors, inhibiting
the replacement of lost senescent cells in all tissues from progenitor
and stem cell populations. These growth factor starved stem cells
cannot differentiate and repopulate lost cells without enough growth
factors, so I suspect CR adults just wither away and become frail at a
faster rate. Osteopenia would be an easily detectable early warning
sign of this trend.

Lowest mortality is at BMI 24.6 - 29.8 in elderly women PMID 17395851

Lowest mortality is at BMI 24.0 in elderly men PMID 12859029

So, best to ignore all this data and practice the religion of Faith
Based Moderate Calorie Restriction. Leave the science to the faithless
heathens.
JLC

Andrew B. Chung, MD/PhD · Guest

neighbor jc101 wrote:
[quote]neighbor fr.r...@free.fr wrote:

I definitely adopt this name: too cool "Faith Based Moderate Caloric
Restrictionnists' !!!
In fact since a double blind placebo controlled study regarding CR
with humans is totally
impossible, the only actual solution is to believe that results from
animals can extend to
humans; the future will tell us if this faith was right.

By the way, the full text from this study is very interesting and ask
a lot of questions

Francois Rose

I am glad that this descriptive title FBMCR - Faith Based Moderate
Calorie Restriction is appealing.

Since the rodent data clearly shows that effective CR (40% less -
daily 1500 calories in man) started in mid aged mice shortens
lifespan : "The shift from AL-->CR increased mortality in 17- and 24-
month-old mice..." it definitely requires a "leap of faith" to think
that effective CR will increase lifespan used in middle aged or
elderly adults, suggesting characteristics of religion. This "moderate
CR" is a fine "religion of deprivation" for those for whom it is
psychologically important.

As long as these "moderate CR" adults don>t move into "effective
CR" (which is 40% off calories, BMI 18.5 or below) they will probably
not shorten lifespan too much, as occurred in this study. I suspect
that the means by which effective CR shortens lifespan initiated in
adults is by causing low IGF-1 and other growth factors, inhibiting
the replacement of lost senescent cells in all tissues from progenitor
and stem cell populations. These growth factor starved stem cells
cannot differentiate and repopulate lost cells without enough growth
factors, so I suspect CR adults just wither away and become frail at a
faster rate. Osteopenia would be an easily detectable early warning
sign of this trend.

Lowest mortality is at BMI 24.6 - 29.8 in elderly women PMID 17395851

Lowest mortality is at BMI 24.0 in elderly men PMID 12859029

So, best to ignore all this data and practice the religion of Faith
Based Moderate Calorie Restriction. Leave the science to the faithless
heathens.
[/quote]
Smarter to understand that calories have no practical utility either
in the sale or consumption of food.

A true scientist knows to weigh food in order to accurately quantify
it:

http://groups.google.com/group/sci.med.cardiology/msg/3558812d72ab4e17?

Truth is simple.

May you and other dear neighbors have a blessedly wonderful 2008th
year since the birth of our LORD Jesus Christ as our Messiah, the Son
of Man ...

.... by being hungrier:

http://groups.google.com/group/sci.med.cardiology/msg/f891e617d10bd689?

Hunger is wonderful ! ! !

It>s how we know what GOD desires, which is all that is good.

Yes, hunger is our knowledge of good versus evil that Adam and Eve
paid for with their and our immortal lives.

"Blessed are you who hunger NOW...

.... for you will be satisfied." -- LORD Jesus Christ (Luke 6:21)

Amen.

Here is a Spirit-guided exegesis of Luke 6:21 given in hopes of
promoting much greater understanding:

http://groups.google.com/group/sci.med.cardiology/msg/cc2aa8f8a4d41360?

Be hungry... be healthy... be hungrier... be euglycemic...

Marana tha

Prayerfully in the awesome name of our Messiah, LORD Jesus Christ,

Andrew <><
--
http://groups.google.com/group/sci.med.cardiology/msg/117245343707310e?

Andrew B. Chung, MD/PhD · Guest

convicted friend Guy (g...@consolidated.net) wrote:
[quote]
A diabetic can eat anywhere if they do what they
they should do.

A diabetic has to deal with all or they will lose.

It has so little to do with what or where they eat.

It has to do with how much they eat...
[/quote]
*** Bingo ***

Now there is at least one diabetic posting on ASD that knows the
truth :-)

Laus Deo ! ! !

May you and dear neighbors, friends, and brethren have a blessedly
wonderful 2008th year since the birth of our LORD Jesus Christ as our
Messiah, the Son of Man ...

.... by being hungrier:

http://groups.google.com/group/sci.med.cardiology/msg/f891e617d10bd689?

Hunger is wonderful ! ! !

It>s how we know what GOD desires, which is all that is good.

Yes, hunger is our knowledge of good versus evil that Adam and Eve
paid for with their and our immortal lives.

"Blessed are you who hunger NOW...

.... for you will be satisfied." -- LORD Jesus Christ (Luke 6:21)

Amen.

Here is a Spirit-guided exegesis of Luke 6:21 given in hopes of
promoting much greater understanding:

http://groups.google.com/group/sci.med.cardiology/msg/cc2aa8f8a4d41360?

Be hungry... be healthy... be hungrier... be euglycemic...

Marana tha

Prayerfully in the awesome name of our Messiah, LORD Jesus Christ,

Andrew <><
--
http://groups.google.com/group/sci.med.cardiology/msg/3558812d72ab4e17?

Andrew B. Chung, MD/PhD · Guest

http://groups.google.com/group/sci.med.cardiology/msg/c64fbf65d899cb8e?

<><

http://groups.google.com/group/sci.med.cardiology/msg/4128be9f9918d825?

Taka · Guest

And to prevent cartilage degeneration you don>t want to supplement
with Omega-3 but rather Omega-9 fatty acids ! Here is the evidence:

http://www.freepatentsonline.com/6765020.html

Mead acid for osteoarthritis, your own body will produce it if you
avoid any major source of the EFAs in the diet. Taka

Olafur Pall Olafsson · Guest

On Jun 26, 1:40 pm, jc101 <uniqueprodu...@comcast.net> wrote:
[quote]On Jun 25, 8:59 pm, Olafur Pall Olafsson <olafurp...@yahoo.com> wrote:

Hi Jay,

On Jun 23, 1:10 pm, jc101 <uniqueprodu...@comcast.net> wrote:

Higher insulin production as a problem is apparently not understood by
those who eat all their daily calories at one meal, rather than spread
out at three meals. Calories taken all at one meal increase the
instant insulin requirements and serum levels, which is obviously
detrimental, compared to smaller meals each with lower insulin
requirements.

While it is generally true for glucose I don>t think it is true for
insulin that a single large spike is any more harmful than several
small ones over the day as long as the area under the curve for
insulin is the same in both scenarios. I have not seen any evidence
that this is the case nor that the harm caused by insulin is non-
linear like that of glucose. If you have any evidence of this please
provide it.

The total amount of insulin (the insulin area under the curve) might
be a bit lower in people eating several meals per day than in those
that eat one meal a day.http://pmid.us/10022396issuggestive of
this. In that study subjects eating one meal a day had approximately
the same insulin area under the curve than those eating the same food
divided to three smaller meals a day. Here is the relevant figure from
the full text:http://jcem.endojournals.org/cgi/content-nw/full/84/2/428/F1

But that paper is lacking in that insulin was not measured during
sleep, only till 10pm. Since the subjects ate their single daily meal
at 6pm their glucose and insulin levels had not returned to fasting
levels at 10pm. The result is that at 10pm the group eating one meal a
day had about 3 times higher insulin level than the group eating three
meals a day. If their insulin level did not return to fasting level
quickly then it is reasonable to expect the one meal a day group to
have had a higher AUC for insulin than the group eating three meals a
day. On the other hand the insulin level in the group eating three
meals a day, albeit lower, also had not returned to fasting levels.
Although this is not as likely IMO it is also possible that they had a
higher AUC for insulin, if f.ex. the fasting insulin in the one meal
per day group dropped fairly quickly after 10pm to a level lower than
that of the three meal per day group.

Again while this study suggests that the 24h AUC for insulin will be
higher in those eating fewer meals per day it is not conclusive. I
have yet to see concrete evidence for this being the case. If you have
any such evidence please provide it.

However even if the AUC for insulin is bit higher in those eating one
meal per day than in those eating 2 or more meals per day I still
think eating one meal per day is more beneficial as long as the person
has good insulin sensitivity. This last is important since of course
for someone with poor insulin sensitivity, or a diabetic patient,
eating one meal per day may be very harmful because of the large blood
glucose spike the single meal might cause. But for those with good
insulin sensitivity I do think the benefit of being in a fasted state
for most of the day, where glucose and insulin are low enough to allow
stimulation of autophagy, outweighs the potential negative effects of
having a higher insulin AUC and having one large spike in insulin
daily.

Thanks for the study link, hadn>t seen it. It shows that those eating
all their calories in one meal (binge eaters) had higher fasting
glucose levels.
[/quote]
No it does not. It only shows that those who eat all their calories in
one meal and eat this one meal *late in the day* have a higher fasting
glucose upon wakening. It does not mean that those who consume one
meal daily and eat it in the middle of the day or early in the day
will necessarily have a higher fasting glucose upon wakening than
those who consume three meals per day. The fact that they consumed
their single meal late in the day is most likely the reason for their
higher fasting glucose upon wakening. Had they consumed their single
meal earlier in the day I don>t think they would>ve had any higher
fasting blood glucose upon wakening. It might even have been lower. In
addition while the subjects who consumed their calories in a single
daily meal late in the day had a higher fasting glucose upon wakening
their glucose kept declining slowly during the day up until the onset
of their daily meal. The result is that the fasting glucose just
before the start of the meal was even lower than the fasting glucose
upon wakening in the three meals per day group. This suggests to me
that if the single daily meal had been consumed in the morning the
fasting glucose measurement taken upon wakening would>ve been closer
to the daily meal and probably have been lower in the one meal per day
group than in the three meals per day group.

[quote]I am going to post it here, explains why binge eaters
get sleepy after they pig out,
[/quote]
The high insulin during the single meal could explain the sleepiness
some experience but it could also be caused by large amounts of blood
being directed towards the digestive system to digest all the food and
thus less being available for the brain.

[quote]the higher fasting glucose should scare
anyone.
[/quote]
It sure doesn>t scare me. It is not high considering that the the
subjects ate the single meal late in the day. In addition because
their glucose keeps getting lower until the onset of their daily meal,
all in all the mean blood glucose in the group eating a single daily
meal was considerably lower than that of the three meals per day
group. The effect was very significant and is evident from this quote
from the full text:

"The mean glucose level across the duration of the study was
significantly lower in the binge patients because they did not have
postprandial increases after breakfast and lunch (normal mean, 107 ±
2; binge, 97 ± 2 mg/dL; P = 0.003)."

This is quite a large reduction in mean glucose and should reduce
glycation considerably. In fact this study, when I first read it a few
years ago, was the main catalyst that caused me to start eating twice
daily rather than three or more times.

[quote]You are right, that there is not good data on the total AUC
insulin regarding binge eaters. But it seems logical. 3 meals evolved
for good reason.
[/quote]
I don>t think three meals have evolved much. Evolutionary the act of
regularly eating three meals per day is a very recent phenomenon.
Humans have adapted to eating three meals per day but their body has
not evolved to eat three meals per day anymore than they have evolved
to drive cars or use computers.

[quote]And there is no reason to think that binge eating leads to increased
autophagy during the balance of the day.
[/quote]
That is not true. Just the fact that gluconeogenesis is increased
considerably in humans upon fasting for several hours is enough
evidence based on the mechanism of gluconeogenesis and autophagy.

[quote]The rodent data shows that
lowered blood lipids and glucose are required for a couple of weeks
(human equivalent) to increase the autophagy. This is a pipe dream.
[/quote]
To think it is equivalent to a couple of weeks is absurd. Humans and
rodents may have a large difference in lifespan but on a cellular
level they are very similar. The metabolism of rodents is only a few
times faster than that of humans. Studies that show increased
gluconeogenesis and increased protein breakdown in humans upon several
hours of fasting are basically proof that autophagy is increased by
short term fasting. If it is not then where on earth do the amino
acids that serve as a substrate for gluconeogenesis come from? The
body does not store amino acids! It breaks tissues down through
autphagy to give supplies of amino acids that in turn serve as a
substrate for glucose along with stored glycogen when the body is in a
fasting state and glucose is lacking.

Jouko · Guest

Taas juttu josta en ole yhtään "virallista uutista" bongannut. Mutta yhtä
kaikki Venäjää kohauttaa tilanne siitä, että koko maasta on torakat kadonnet
kuin taikaiskusta kaikkialta. Tässä on jotain todella outoa nyt kyseessä.
Torakka on äärimmäisen vanhaa eläinpopulaatiosuuntaa. Jolla on
selkäytimissään sellaista käyttäytymismallia, jota harvalla eläimellä on.
Toisaalta torakkaa pidetään aivan yleisesti äärimmäisen herkkänä, suorastan
legendaarísen tarkkana hahmottamaan elinympäristönsä vaaratilannemuutoksia.
Muistamme miten mm. norsut, ja viisaammat eläimet pelastautui taanoisesta
tsunamista pakenemalla ennakoiden laumoin vuorille, siksi uutinen torakoista
"huolestuttaa" yli uutiskynnysten? Torakan toki pitäisi olla varsin kestävä
myös säteilyn suhteen. Ymmärtääkseni kuolleina näitä ei ole havaittu
mainittavasti? Eli, eli täytyy miettiä mistä voisi olla kyse.

Torakan keskeinen maailmansa hahmotus on kyky paeta oivallisesti uhista, ja
jopa äärimmäisen harvinaisista tulevista megauhista, koska on sukuna
säilynyt lukuisista mm. maan mangneettinapavaihteluista, meteorituhoista ja
megatulivuorijaksoennakoinneista. Väistämättä tulee mieleen, että noin laaja
käyttäytymismuutos heijastelee samaisesta mekaniikasta joka tappoi vuosi
sitten mehiläiset. Eli torakan antenisysteemi on syöttänyt selkeät
koordistot menneisyyden hämäristä, että nyt mitattavat epänormaalin rajut
ionosfäärien sähkökenttämuutosvaihtelut ennakoivat tuhokasvua! Voidaan ottaa
esimerkiksi menneisyystilanteet, joissa maapallon mangnettinapa vaihtuu
käänteiseksi. Kuten usein on tehnyt menneinä vuosimiljoonina. Miten
alkeisniveljalkainen reagoi?

Aivan oikein herkällä mangneettimuutoskiihtymisen anturoinnillaan torakat
tajuaa genomaperintönä selkäydinpohjalta muutoskytkökset. Osaavat näin
hakeutua luoliin, onkaloihin maan alle, paikoihin joissa ruokaa on, mutta
päällä on massiivista massaa valtavat määrät. Nimittäin kun maan
mangneettisuoja muuttu on hetkenaikaa tilanne sellainen, että tappavat
avaruuden säteilyfotonimeret tulevat maan pintaan asti! KAIKKI elämä joka ei
ole ehtinyt hakeutua suojaan kuolee varoittamatta. Tässä on keskeisintä myös
ihmisten tajuta, että maailman läpimätäkorruptoituneisiin
ydinturvavirannomaisiin ja vastaaviin "ydinsuojeluun huijattuihin" ei voi
enää edes nimellisesti luottaa! Menneisyydessä siis vain ne
torakkasukupolvet, jotka tajusi ennakkoiden reagoida selvisivät jatkamaan
sukua. Ja nyt on samantyyppistä varoitusta tullut historian
geeniperintötaustasta tuntosarviin! No nyt toki ei ole kyse maan
mangneettikenttämuutoksista, ei toki.

Vaan prosessista, joka tuhoaa parhaillaan esim. Antarktiksen
otsonikerroksia. Pakottaa USA:n lentokonekannoista puolet maahan tuosta
vaan! Hävittää mehiläismiljardipopulaatioita viikoissa ja. .. .Niin no
torakat hakeutuessaan pois on viisaampia toki kuin ongelman itselleen
aiheutaneet ydininsinöörit, jotka eivät sitten MILLÄÄN oivalla miksi Itämeri
NYT kuolee vuodessa parissa, miksi metastabiilitaustamme kymmenkertaistuu,
miksi Atsteekkien kalenterit varoittaa. ..No tulevaisuus on toki omaan
tuhoonsa kansansa kyöräävää ydintehdasmaista järjenkäyttöä oivaltaviempien
käsissä. Ja evolutionaarisesti ilman muuta hyvä niin. Miksei maailma
"eliminoisi" ydinloistartuttajat kamaraltaan juuri kutkan räjähtäessä
hallitsemattomuuksiinsa lähivuosina? Jos näin säästyy edes torakoista osa
jatkamaan ydinvapaampaa tulevaisuutta niin häviäjiä on yndisyyllisihmiset,
mutta luonto itsessään saa mahdolisuuden hankkia kamaralleen elinvoimaa joka
ei ydinharhaansa tukehdu! Nukkukaa hyvin, koska pian "ehkä" ette voi.

Paul Antonik Wakfer · Guest

On Jun 23, 9:40 pm, Paul Antonik Wakfer <p...@morelife.org> wrote:
[quote]On Jun 23, 1:11 am, Thomas Carter <tomcarter...@yahoo.com> wrote:

On Jun 22, 1:37 pm, Paul Antonik Wakfer <p...@morelife.org> wrote:

The following published letter gives a basis for understanding the
evidence that serum glucose spikes are far more harmful than would be
expected merely from their contribution to the total glycation
effects.

---------------- Start of publication ------------------

Free Radic Biol Med. 2008 Jun 1;44(11):1970. Epub 2008 Mar 18.
Deleterious effects due to glucose or to triose phosphates.
Fridovich I.
Department of Biochemistry, Box 3711, Duke University Medical Center,
Durham, NC
27710, USA.
PMID: 18394431

Article

Many of the deleterious consequences of uncontrolled diabetes mellitus
have been attributed to nonenzymatic glycation and such glycation
reactions have been extensively studied [1]. Nakahata et al. [2] have
recently reported that a 15-min exposure of rat brain slices to 20 mM
D-glucose resulted in increased production of superoxide with
decreased arteriolar vasodilation in response to acetylcholine.
Strikingly 20 mM L-glucose was without effect. The nonenzymatic
glycation reaction begins with the coupling of the potential carbonyl
on C-1 of glucose with the amino groups on proteins or nucleic acids.
Since the designations D or L pertain to sterio isomerism at C-5 of
the glucose, it must be expected that D- or L-glucose will participate
in nonenzymatic glycation reactions to the same degree. Moreover
glycation by glucose is a slow reaction and could not have proceeded
significantly in 15 min. It follows that the effects reported by
Nakahata et al. could not have been due to nonenzymatic glycations by
D-glucose.

Glucose exists in solution overwhelmingly in the pyranose form, in
which the carbonyl on C-1 cyclizes by hemiacetal formation with the
hydroxyl on C-5. This masking of the carbonyl explains the slugginess
of nonenzymatic glycation. D-Glucose but not L-glucose can be
converted, by the enzymes of the Embden-Meyerhoff pathway, to triose
phosphates, for which cyclization by hemiacetal formation is not
possible. Hence the triose phosphates are much more prone to
condensation with amino groups than are hexoses such as glucose.
Moreover the triose phosphates can tautomerize to enediols that are
likely to autooxidize with formation of superoxide, hydrogen peroxide,
and diketones [3], [4] and [5]. For these reasons the effects reported
by Nakahata et al. [2] were most probably due to the triose phosphates
derived from D-glucose rather than to D-glucose itself.

A remaining puzzle is why 20 mM glucose was harmful while 5 mM was
not. The rate of entry of D-glucose into the glycolytic pathway is by
way of the hexokinase- or glucokinase-catalyzed phosphorylations.
Hexokinase exhibits a Km for D-glucose of approximately 0.1 mM and is
subject to allosteric inhibition by glucose 6-phosphate. In contrast
glucokinase exhibits a Km for D-glucose of 10 mM and is not inhibited
by glucose 6-phosphate. Thus at 20 mM glucose the glycolytic flux
would not be regulated by the steady-state level of glucose 6-
phosphate, and the formation of the triose phosphates would be higher
than the 5-fold difference in the concentration of the D-glucose
applied by Nakahata et al. [2] It is fortunate that the equilibrium of
the aldolase reaction lies far toward fructose 1,6-bisphosphate. Were
this not the case the concentration of the triose phosphates would be
higher and the deleterious effects of glucose would be apparent even
at the normal 4 mM.

References

[1] G. Misciagna, G. De Michelle and M. Trvisan, Nonenzymatic glycated
proteins in the blood and cardiovascular disease, Curr. Pharm. Des. 13
(2008), pp. 3688–3695.

[2] K. Nakahata, H. Kinoshita, T. Azma, N. Matsuda, K. Hama-Tomioka,
M. Haba and Y. Hatano, Propofal restores brain microvascular function
impaired by high glucose via the decrease in oxidative stress,
Anesthesiology 108 (2008), pp. 269–275.

[3] T. Yamaguchi and K. Nakagawa, Mutagenicity of and formation of
oxygen free radicals by trioses and glyoxal derivatives, Agric. Biol.
Chem. 47 (1983), pp. 2461–2465.

[4] T. Mashino and I. Fridovich, Mechanism of cyanide-catalyzed
oxidation of alpha-ketoaldehydes and alpha-ketoalcohols, Arch.
Biochem. Biophys. 252 (1987), pp. 163–170.

[5] T. Mashino and I. Fridovich, Superoxide radical initiates the
autoxidation of dihydroxyacetone, Arch. Biochem. Biophys. 254 (1987),
pp. 547–551.

---------------- End of publication -----------

However, while the biochemical analysis above is brilliant, note the
illogic of the last two sentences, which effectively reverse the cause
and effect of physical reality and evolution. Rather they should have
been written:

"The likely reason why 4 mM of serum glucose is the more normal and
healthier value is because the equilibrium of the aldolase reaction
lies far toward fructose 1,6-bisphosphate, which makes the
concentration of the triose phosphates and the consequent deleterious
effects of glucose much lower than at the higher value of 20 mM that
showed such strong negative effects."

--Paul Wakfer

MoreLife for the rational -http://morelife.org
Reality based tools for more life in quantity and quality
The Self-Sovereign Individual Project -http://selfsip.org
Self-sovereignty, rational pursuit of optimal lifetime happiness,
individual responsibility, social preferencing & social contracting

Hi Paul,

The three trioses produced by metabolism of glucose are pyruvate,
lactate, and dihydroxyacetone. None are dangerous. Pyruvate has been
studied as a neuroprotectant. I don’t know much about
dihydroxyacetone, but it’s a three carbon chain with little else
attached. I would imagine it’s quickly fed to acyl-coenzyme A and
metabolized for energy. Lactate is reduced pyruvate and builds up in
conditions of hi energy use such as strenuous exercise, and glucose
intoxicated rat brain slices. It was long thought to be the cause of
lactic acidosis, but this is now considered to be caused by proton
leak from the mitochondria associated with hi NAD+ thruput.

This would likely be the cause of the stress seen in the rat brain
slices and would have nothing to do with glycation or “triose”cation..
The irony here is that in this acidic invironment glucose becomes more
acyclic and thus is more prone to glycate proteins. The letter seems
to highly speculative at the best, and IMO not well thought thru.
Human in vivo relevance at physiological oxygen pressure and with
blood flow to remove lactate would be a long shot.

Tho I have only one ref at hand, I think the dangers of postprandial
hyperglycemia are thought to be free glucose in the plasma due to
overload of red blood cells which are the primary glucose carriers in
the blood stream. Capillaries are only one third the diameter of red
blood cells, and when the latter squeeze thru the capillary they
extend it, opening up pores so that substances on their membranes can
pass thru. Free glucose is more likely to lodge in the vascular walls
causing the well known coronary, renal, optical and vascular problems
associated with diabetes. Also important are excess production of
insulin, a toxic substance, and reactive post prandial hypoglycemia
caused by the hi insulin production.

Thomas

Am J Physiol. 1984 Mar;246(3 Pt 2):R289-98. Links
Red blood cell as glucose carrier: significance for placental and
cerebral glucose transfer.
Jacquez JA.
At plasma glucose values of 5 mM (90 mg/100 ml) the
maximum glucose transport capacity of the human red cell membrane is
12,000 times the rate of glucose utilization by the red blood cell.
Mammals, other than primates, that have been tested have a comparable
high-capacity system during fetal life, which is lost soon after
birth. It has been suggested that the availability of the water space
of the red blood cell for distribution of glucose facilitates transfer
across the placenta during fetal life in all mammals and across the
blood-brain barrier in adult primates. Though plausible, more
comparative studies of glucose transport in red blood cells of other
species and direct experimental evaluations of the contribution of the
red blood cell to glucose transfer across the placenta and the blood-
brain barrier are needed.
PMID: 6367491

Irwin Fridovich PhD is James B Duke Prof Emeritus of Biochemistry. He
has 406 papers listed on PubMed alone one of which is the following
highly important position paper coauthored by many other leading aging
researchers.

Aging Clin Exp Res. 2004 Apr;16(2):104-11; discussion 111-2.

The aging factor in health and disease: the promise of basic research
on aging.

Butler RN, Warner HR, Williams TF, Austad SN, Brody JA, Campisi J,
Cerami A,
Cohen G, Cristofalo VJ, Drachman DA, Finch CE, Fridovich I, Harley CB,
Havlik RJ,
Martin GM, Miller RA, Olshansky SJ, Pereira-Smith OM, Smith JR, Sprott
RL, West
MD, Wilmoth JR, Wright WE.

International Longevity Center-USA, Alliance for Health & the Future,
and
Department of Geriatrics, Mount Sinai Medical Center, New York, NY
10028, USA.
Robe...@ilcusa.org

PMID: 15195984

Here is a dialog that I just had with Prof Fridovich:------- Original Message --------
Subject: Re: Re your letter "Deleterious effects due to glucose or to

triose phosphates."
Date: Mon, 23 Jun 2008 12:45:55 -0400
From: Irwin Fridovich <fridov...@biochem.duke.edu
To: Paul Wakfer <p...@morelife.org
References: <485FC1BE....@morelife.org

Dear Paul,
My letter was based on reasonable chemistry and
biochemistry.The thoughts in it were intended to stimulate other
scientists to think about the toxicity of hyperglycemia in a
different way.If the two individuals, who did not find my ideas
sensible, will communicate directly with me I shall be glad to
consider their criticisms.
Sincerely,
Irwin
On Jun 23, 2008, at 11:31 AM, Paul Wakfer wrote:

Dear Prof Fridovich,

Since I had always been on the lookout for mechanisms by which
serum glucose spikes cause non-linearly more harm than would be
found simply by their contribution to the AUC glycation pressure, I
found your letter to be very important and posted it to the
newsgroup sci.life-extension.

http://groups.google.com/group/sci.life-extension/browse_frm/thread/1...

The responses I received are from two posters who appear to always
think that they know better than everyone else, the first clearly
stating that your ideas were just so much nonsense.
I would be obliged if you would make a direct response to that
reply (by Thomas Carter). If you do not think that it is worth your
time to response to such people on such a venu, then I fully
understand.

--Paul Wakfer

MoreLife for the rational -http://morelife.org
Reality based tools for more life in quantity and quality
The Self-Sovereign Individual Project -http://selfsip.org
Self-sovereignty, rational pursuit of optimal lifetime happiness,
individual responsibility, social preferencing & social contracting

Thomas, if you get a reply from Fridovich, I would appreciate it if
you would post it here so that we are all more enlightened.

--Paul
[/quote]
I think that the following additional dialog with Fridovich is worth
posting both because of its relevance to the subject of this thread
and also to my own comment relating to the distortion of reality
engendered by the last two sentences of Fridovich>s original published
comment letter.

Even though Fridovich unfortunately used only the "top" replying
method, I have reordered the text so that readers here can more easily
follow the dialog.

-------- Original Message --------
Subject: Re: Re your letter "Deleterious effects due to glucose or to
triose phosphates."
Date: Tue, 24 Jun 2008 12:57:46 -0400
From: Irwin Fridovich <fridovich@biochem.duke.edu>
To: Paul Wakfer <paul@morelife.org>
References: <485FC1BE.503@morelife.org>
<E514B83B-808D-4602-89FD-2BE2FE1BF52F@biochem.duke.edu> <4860543A.
3010906@morelife.org>
<E668E891-34DA-43F2-9624-7EE8377DB73D@biochem.duke.edu>
<48610B90.8090205@morelife.org>

[quote]On Jun 23, 2008, at 9:56 PM, Paul Wakfer wrote:

Dear Irwin,

Thanks for replying. I have passed on your suggestion to Thomas
Carter, but I do not expect that he will have the courage to
communicate directly with you. If he does, your response, which
I have requested that he post to sci.life-extension, should be
enlightening to all readers there.

Did you read as far as the end of my own post of your letter
where I made a small critique of your two sentences beginning
with "It is fortunate"? If so, I would be interested to have
your response. I made that criticism because I am convinced that
always maintaining the correct perspective of cause and effect
is of paramount importance in science. BTW, my on background is
originally in mathematics and theoretical physics (Professor at
University of Toronto), but later self trained in all aspects of
biology and social philosophy related to human life enhancement,
both in quantity and quality.

--Paul
[/quote]
On Jun 24, 2008, at 10:58 AM, Paul Wakfer wrote:
[quote]On 06/24/2008 10:02 AM, Irwin Fridovich wrote:
Dear Paul,
If you will clarify what you want me to comment on I will
respond.

Dear Irwin,

I am a little confused about what was unclear in my explanation of
my request. The best that I can do is to assume that you were
unable to access my message posted to sci.life-extension and
viewable by clinking the link that I provided, specifically http://
groups.google.com/group/sci.life-extension/browse_frm/thread/
17068151710ac69b#

Assuming that is the case, here is the text of your letter to which
I refer and my critique of it with respect to which I am interested
in a comment from you.

Your letter ended with:

"It is fortunate that the equilibrium of
the aldolase reaction lies far toward fructose 1,6-bisphosphate. Were
this not the case the concentration of the triose phosphates would be
higher and the deleterious effects of glucose would be apparent even
at the normal 4 mM."

My critique of this was:

However, while the biochemical analysis above is brilliant, note the
illogic of the last two sentences, which effectively reverse the cause
and effect of physical reality and evolution. Rather they should have
been written:

"The likely reason why 4 mM of serum glucose is the more normal and
healthier value is because the equilibrium of the aldolase reaction
lies far toward fructose 1,6-bisphosphate, which makes the
concentration of the triose phosphates and the consequent deleterious
effects of glucose much lower than at the higher value of 20 mM which
showed such strong negative effects."

So my criticism is mainly about the use of the word "fortunate" to
describe the homoestatic conditions of evolved lifeforms. This is,
of course, a point of philosophy of science, but one with respect
to which I think it is extremely important to maintain the correct
perspective.

--Paul
[/quote]
Dear Paul,
I agree that your wording is better.Certainly the
equilibrium
of the aldolase reaction is a direct consequence of the free energy
change associated with the cleavage of glucose1,6 bisphosphate into
the two triose phosphates and the enzyme catalyzing that reaction
could not change that.It would have been wiser to omit the entire
comment.I blame it on poetic licence.It was a way to emphasize the
point that the trioses are more dangerous than the parent glucose
compound.
Thanks for your comment.
Irwin
------------ end of quoted dialog -------------

Note the last sentence of the above which reemphasizes what Fridovich
maintained in his published comment (and I thought to be important).
Once again, I urge Thomas Carter to correspond with Fridovich in order
to resolve their differences. The requirements of having valid
knowledge demand such action.

--Paul Wakfer

MoreLife for the rational - http://morelife.org
Reality based tools for more life in quantity and quality
The Self-Sovereign Individual Project - http://selfsip.org
Self-sovereignty, rational pursuit of optimal lifetime happiness,
individual responsibility, social preferencing & social contracting

rs1000b@yahoo.com · Guest

On Jun 23, 9:40 pm, Paul Antonik Wakfer <p...@morelife.org> wrote:
[quote]On Jun 23, 1:11 am, Thomas Carter <tomcarter...@yahoo.com> wrote:

On Jun 22, 1:37 pm, Paul Antonik Wakfer <p...@morelife.org> wrote:

The following published letter gives a basis for understanding the
evidence that serum glucose spikes are far more harmful than would be
expected merely from their contribution to the total glycation
effects.

---------------- Start of publication ------------------

Free Radic Biol Med. 2008 Jun 1;44(11):1970. Epub 2008 Mar 18.
Deleterious effects due to glucose or to triose phosphates.
Fridovich I.
Department of Biochemistry, Box 3711, Duke University Medical Center,
Durham, NC
27710, USA.
PMID: 18394431

Article

Many of the deleterious consequences of uncontrolled diabetes mellitus
have been attributed to nonenzymatic glycation and such glycation
reactions have been extensively studied [1]. Nakahata et al. [2] have
recently reported that a 15-min exposure of rat brain slices to 20 mM
D-glucose resulted in increased production of superoxide with
decreased arteriolar vasodilation in response to acetylcholine.
Strikingly 20 mM L-glucose was without effect. The nonenzymatic
glycation reaction begins with the coupling of the potential carbonyl
on C-1 of glucose with the amino groups on proteins or nucleic acids.
Since the designations D or L pertain to sterio isomerism at C-5 of
the glucose, it must be expected that D- or L-glucose will participate
in nonenzymatic glycation reactions to the same degree. Moreover
glycation by glucose is a slow reaction and could not have proceeded
significantly in 15 min. It follows that the effects reported by
Nakahata et al. could not have been due to nonenzymatic glycations by
D-glucose.

Glucose exists in solution overwhelmingly in the pyranose form, in
which the carbonyl on C-1 cyclizes by hemiacetal formation with the
hydroxyl on C-5. This masking of the carbonyl explains the slugginess
of nonenzymatic glycation. D-Glucose but not L-glucose can be
converted, by the enzymes of the Embden-Meyerhoff pathway, to triose
phosphates, for which cyclization by hemiacetal formation is not
possible. Hence the triose phosphates are much more prone to
condensation with amino groups than are hexoses such as glucose.
Moreover the triose phosphates can tautomerize to enediols that are
likely to autooxidize with formation of superoxide, hydrogen peroxide,
and diketones [3], [4] and [5]. For these reasons the effects reported
by Nakahata et al. [2] were most probably due to the triose phosphates
derived from D-glucose rather than to D-glucose itself.

A remaining puzzle is why 20 mM glucose was harmful while 5 mM was
not. The rate of entry of D-glucose into the glycolytic pathway is by
way of the hexokinase- or glucokinase-catalyzed phosphorylations.
Hexokinase exhibits a Km for D-glucose of approximately 0.1 mM and is
subject to allosteric inhibition by glucose 6-phosphate. In contrast
glucokinase exhibits a Km for D-glucose of 10 mM and is not inhibited
by glucose 6-phosphate. Thus at 20 mM glucose the glycolytic flux
would not be regulated by the steady-state level of glucose 6-
phosphate, and the formation of the triose phosphates would be higher
than the 5-fold difference in the concentration of the D-glucose
applied by Nakahata et al. [2] It is fortunate that the equilibrium of
the aldolase reaction lies far toward fructose 1,6-bisphosphate. Were
this not the case the concentration of the triose phosphates would be
higher and the deleterious effects of glucose would be apparent even
at the normal 4 mM.

References

[1] G. Misciagna, G. De Michelle and M. Trvisan, Nonenzymatic glycated
proteins in the blood and cardiovascular disease, Curr. Pharm. Des. 13
(2008), pp. 3688–3695.

[2] K. Nakahata, H. Kinoshita, T. Azma, N. Matsuda, K. Hama-Tomioka,
M. Haba and Y. Hatano, Propofal restores brain microvascular function
impaired by high glucose via the decrease in oxidative stress,
Anesthesiology 108 (2008), pp. 269–275.

[3] T. Yamaguchi and K. Nakagawa, Mutagenicity of and formation of
oxygen free radicals by trioses and glyoxal derivatives, Agric. Biol.
Chem. 47 (1983), pp. 2461–2465.

[4] T. Mashino and I. Fridovich, Mechanism of cyanide-catalyzed
oxidation of alpha-ketoaldehydes and alpha-ketoalcohols, Arch.
Biochem. Biophys. 252 (1987), pp. 163–170.

[5] T. Mashino and I. Fridovich, Superoxide radical initiates the
autoxidation of dihydroxyacetone, Arch. Biochem. Biophys. 254 (1987),
pp. 547–551.

---------------- End of publication -----------

However, while the biochemical analysis above is brilliant, note the
illogic of the last two sentences, which effectively reverse the cause
and effect of physical reality and evolution. Rather they should have
been written:

"The likely reason why 4 mM of serum glucose is the more normal and
healthier value is because the equilibrium of the aldolase reaction
lies far toward fructose 1,6-bisphosphate, which makes the
concentration of the triose phosphates and the consequent deleterious
effects of glucose much lower than at the higher value of 20 mM that
showed such strong negative effects."

--Paul Wakfer

MoreLife for the rational -http://morelife.org
Reality based tools for more life in quantity and quality
The Self-Sovereign Individual Project -http://selfsip.org
Self-sovereignty, rational pursuit of optimal lifetime happiness,
individual responsibility, social preferencing & social contracting

Hi Paul,

The three trioses produced by metabolism of glucose are pyruvate,
lactate, and dihydroxyacetone. None are dangerous. Pyruvate has been
studied as a neuroprotectant. I don’t know much about
dihydroxyacetone, but it’s a three carbon chain with little else
attached. I would imagine it’s quickly fed to acyl-coenzyme A and
metabolized for energy. Lactate is reduced pyruvate and builds up in
conditions of hi energy use such as strenuous exercise, and glucose
intoxicated rat brain slices. It was long thought to be the cause of
lactic acidosis, but this is now considered to be caused by proton
leak from the mitochondria associated with hi NAD+ thruput.

This would likely be the cause of the stress seen in the rat brain
slices and would have nothing to do with glycation or “triose”cation..
The irony here is that in this acidic invironment glucose becomes more
acyclic and thus is more prone to glycate proteins. The letter seems
to highly speculative at the best, and IMO not well thought thru.
Human in vivo relevance at physiological oxygen pressure and with
blood flow to remove lactate would be a long shot.

Tho I have only one ref at hand, I think the dangers of postprandial
hyperglycemia are thought to be free glucose in the plasma due to
overload of red blood cells which are the primary glucose carriers in
the blood stream. Capillaries are only one third the diameter of red
blood cells, and when the latter squeeze thru the capillary they
extend it, opening up pores so that substances on their membranes can
pass thru. Free glucose is more likely to lodge in the vascular walls
causing the well known coronary, renal, optical and vascular problems
associated with diabetes. Also important are excess production of
insulin, a toxic substance, and reactive post prandial hypoglycemia
caused by the hi insulin production.

Thomas

Am J Physiol. 1984 Mar;246(3 Pt 2):R289-98. Links
Red blood cell as glucose carrier: significance for placental and
cerebral glucose transfer.
Jacquez JA.
At plasma glucose values of 5 mM (90 mg/100 ml) the
maximum glucose transport capacity of the human red cell membrane is
12,000 times the rate of glucose utilization by the red blood cell.
Mammals, other than primates, that have been tested have a comparable
high-capacity system during fetal life, which is lost soon after
birth. It has been suggested that the availability of the water space
of the red blood cell for distribution of glucose facilitates transfer
across the placenta during fetal life in all mammals and across the
blood-brain barrier in adult primates. Though plausible, more
comparative studies of glucose transport in red blood cells of other
species and direct experimental evaluations of the contribution of the
red blood cell to glucose transfer across the placenta and the blood-
brain barrier are needed.
PMID: 6367491

Irwin Fridovich PhD is James B Duke Prof Emeritus of Biochemistry. He
has 406 papers listed on PubMed alone one of which is the following
highly important position paper coauthored by many other leading aging
researchers.

Aging Clin Exp Res. 2004 Apr;16(2):104-11; discussion 111-2.

The aging factor in health and disease: the promise of basic research
on aging.

Butler RN, Warner HR, Williams TF, Austad SN, Brody JA, Campisi J,
Cerami A,
Cohen G, Cristofalo VJ, Drachman DA, Finch CE, Fridovich I, Harley CB,
Havlik RJ,
Martin GM, Miller RA, Olshansky SJ, Pereira-Smith OM, Smith JR, Sprott
RL, West
MD, Wilmoth JR, Wright WE.

International Longevity Center-USA, Alliance for Health & the Future,
and
Department of Geriatrics, Mount Sinai Medical Center, New York, NY
10028, USA.
Robe...@ilcusa.org

PMID: 15195984

Here is a dialog that I just had with Prof Fridovich:------- Original Message --------
Subject: Re: Re your letter "Deleterious effects due to glucose or to

triose phosphates."
Date: Mon, 23 Jun 2008 12:45:55 -0400
From: Irwin Fridovich <fridov...@biochem.duke.edu
To: Paul Wakfer <p...@morelife.org
References: <485FC1BE....@morelife.org

Dear Paul,
My letter was based on reasonable chemistry and
biochemistry.The thoughts in it were intended to stimulate other
scientists to think about the toxicity of hyperglycemia in a
different way.If the two individuals, who did not find my ideas
sensible, will communicate directly with me I shall be glad to
consider their criticisms.
Sincerely,
Irwin
On Jun 23, 2008, at 11:31 AM, Paul Wakfer wrote:

Dear Prof Fridovich,

Since I had always been on the lookout for mechanisms by which
serum glucose spikes cause non-linearly more harm than would be
found simply by their contribution to the AUC glycation pressure, I
found your letter to be very important and posted it to the
newsgroup sci.life-extension.

http://groups.google.com/group/sci.life-extension/browse_frm/thread/1...

The responses I received are from two posters who appear to always
think that they know better than everyone else, the first clearly
stating that your ideas were just so much nonsense.
I would be obliged if you would make a direct response to that
reply (by Thomas Carter). If you do not think that it is worth your
time to response to such people on such a venu, then I fully
understand.

--Paul Wakfer

MoreLife for the rational -http://morelife.org
Reality based tools for more life in quantity and quality
The Self-Sovereign Individual Project -http://selfsip.org
Self-sovereignty, rational pursuit of optimal lifetime happiness,
individual responsibility, social preferencing & social contracting

Thomas, if you get a reply from Fridovich, I would appreciate it if
you would post it here so that we are all more enlightened.

--Paul
[/quote]
An author>s permission should be obtained before publishing his
private correspondence to a public forum.

Guest

On 26 juin, 16:09, jc101 <uniqueprodu...@comcast.net> wrote:
[quote]On Jun 26, 6:19 am, fr.r...@free.fr wrote:

On Jun 25, 4:54 pm, jc101 <uniqueprodu...@comcast.net> wrote:

On Jun 24, 4:55 am, fr.r...@free.fr wrote:

On Jun 23, 7:47 pm, jc101 <uniqueprodu...@comcast.net> wrote:

On Jun 23, 11:44 am, fr.r...@free.fr wrote:

On Jun 22, 5:30 pm, jc101 <uniqueprodu...@comcast.net> wrote:

On Jun 21, 11:27 am, Pramesh Rutaji <p297tongue6...@newsguy.com
jc101 wrote:
snip
Gonna be side effects with effective CR. In addition to brittle bones,
depression, lethargy, fatigue, loss of libido, impotence, feeling
cold, and anger,

Could you please give references for your statements otherwise this is
just "faith based rather than science" as you>re saying !!!!

I will bet increased rate of colds, flu, and other
infections are noted as well.

Regarding this statement, I>m very curious to look at your sources
since inhttp://pmid.us/6608731
with full text herehttp://tinyurl.com/6j9wbrthetable2shows
clearly that Restricted (Res + +) old mice have a greater immune
response than ad lib. fed old mice (Fed + +).

The good news is that all these problems can be averted now and the
exact same effective CR results achieved just using about a mg of DNP
at less than 1 cent and maybe a cc of knotweed extract (resveratrol
source) at less than 10 cents daily. After this new DNP article came
out last month, CR just became outmoded altogether, superseded by
mitochondrial protonophore therapy. Remaining practitioners will be
continuing for faith based (or habit) rather than science based
reasons, given the prevalence of noted side effects with effective CR.
Reminds me of when electric lights replaced kerosene lamps. There
always will be a fewwicktrimmersleft around.

The main difference between CR and DNP use is the number of studies
showing (mean and max) lifespan extension with CR and only one study
with DNP showing an increase of 7 % in mean lifespan with only one
specific mouse strain . So currently science is leaning towards CR and
faith is leaning towards DNP use.

If you have evidences regarding CR side effects, please provide them

FranÃ§ois Rose

JLC-
Indeed, that is just what I am asking - if anyone has any data on the
incidence of these side effects that I have heard of anecdotally with
calorie restriction : brittle bones, depression, lethargy, fatigue,
loss of libido, impotence, feeling cold, anger, as well as possible
increased rate of colds, flu, and other infections. I suspect these
data have not been tabulated. Perhaps practitioners would chime in..

Regarding "cold, anger, as well as possible increased rate of colds,
flu, and other infections", your bet is probably wrong as I show you a
study in my former reply that shows that the immune response of CR
mice is better.
Here is another study published in 2007 with primates under CR since
1987 http://pmid.us/17063037
and it>s said that "both males and females (under CR) may benefit
immunologically"

Regarding brittle bones, Paul Wakfer already answered about that.

I>m personnally following a mild CR with only meal each day and
regarding impotence and loss of libido, I>m having sex at least once a
day for at least twelve years. No sign of impotence in view. (I
follow a method described in this book "Taoist Secrets of Love:
Cultivating Male Sexual Energy" by Mantak Chia , Michael Winn )

Regarding cold, it is true I can feel a little bit cold especially
before I eat but I pull on another sweater; where is the point.

Regarding depression, lethargy, fatigue, I>ve never been so
active and
effecient since I>m on mild CR !!!!

Regarding anger, I remember I read sth about this in PubMed but I
can>t find it gain; according to my memories, it was said that the
animals on CR were angrier between them. (That can be easily
understood since their bodies told them that they NEED to eat and
they>ve never decided to eat less calories; it>s not their personal
choice; they are living under the pressure of getting food and they
don>t know when)
Some mechanisms of our human biology seems to be very useful during
starvation moment (like storing fats and carbohydrates), but these
mechanisms are not as useful for my (long term) survival since I
have
a food store near my home and a fridge and a freezer.
Personnally, I>ve decreased gradually my daily calory amount and
regarding anger, the first days after I lessened my calory amount, I
was more angry than usual but I think (and I hope) that it was going
back to my usual mood after a while.

If someone wants to live on 1500 calories a day, and reap the
benefits
to longevity that might be available, go for it. Just saying
there are
side effects, and no evidence of longevity increases without a 40%
reduction of calories have been documented that I know of.

Metformin is a CR mimetic ( http://pmid.us/15247056 )
Moreover, the CR benefits are greater when the reduction of calories
is greater (until some point, of course, maybe 40% or may be 50%)

So my idea is that a mild CR with the use of metformin could have a
synergistic effect and I personally don>t have big problems with my
mild CR and never been so fit and active

Protonophone therapy will replace CR.

If you say so but I will wait for other studies before I try it

By the way, it is spelled "protonophore" in the
studyhttp://pmid.us/18505478

FranÃ§ois Rose> JLC- Hide quoted text -

- Show quoted text -

Thanks for your reply and I am glad that you have found a body weight
that works well for you - it is undoubtedly within normal range BMI
18.5 - 25.0. I feel certain that your calorie intake is not much below
2000.

Yet, the fact remains : 'mild' or 'moderate' lowering of food intake
is not 'Calorie Restriction' yielding longevity benefits. CR in lab
animals is 40% less, 1500 calories in men, yielding BMI 15-18.

So there is no study with a 20% CR with rats!!!!!!!!!!!!!!!!!!!!
Maybe you didn>t search (look below)

No one
reports achieving this, the side effects are probably too tough. So,
that is why I say this mild or moderate food lowering is not proven,
there is no proof of longer life with 20% less calories, it is a
matter of faith without data. But sounds like you are happy with your
body weight, performance and appearance and that is all that matters
within normal BMI range.

from http://pmid.us/17374682 with free full text (see table 1 and
above)
:
"Such results show that there is a strong linear relation between the
degree of restriction and the longevity benefit "

That means a 50 % CR is statistically leading to around a 40 %
increase
in LS
a 25 % CR is statistically leading to around a 20 % increase in LS

By the way, the table from this paper clearly indicates that there are
at least two studies with a 25% CR which result in an increase LS
between 15% and 25 %. (Maybe you could try to search them, JLC)

This is an idea already displayed in this post about BMI:
JLC, you seem to think that a CR between 0% and 35% gives no benefit
in
lifespan and suddenly when you finally get the magic number of 40% CR,
it gives you a 33 % bonus of extra life!!!!!
This paper says exactly the contrary; there seems to be a continuum in
the way you practice CR: if you do mild CR, you>ll have a mild LS
extension and if you practice a strong CR, you>ll have a big LS
extension
(until some point of course: you stop eating, you 'll die soon).
This continuum probably also go like this: if you do a small caloric
increase, you>ll have a small cut in your LS: if you do a big caloric
increase, you>ll have a big cut in your LS

(the redaction of the reply took me some time but the search took me
only 30 minutes on PubMed :the blindest person is the one who doesn>t
want to see, JLC)

The table 2 from the full text of the same study is modeling the GAIN
(Yes JLC the gain!!!) of
year at 2 different levels (15% and 30% CR below control) in relation
to
the age at which restriction is initiated: you might take a look at
it.
Of course it>s only a model; human life is not a double blind
placebo-controlled study (as Ray Kurzweil said) and the result seems
quite modest but if you have something better (if possible well
documented) about life extension, JLC, just tell us.

The paper is also dealing with the importance of activity in rodent
longevity.

Let>s get real here. From the review article you referenced, thank
you, the following :

http://jn.nutrition.org/cgi/content/full/137/4/1078

"...intake would be reduced by 30% from 10 MJ each day to 7 MJ each
day, approximately from 2500 to 1750 kcal/d ...starting the
restriction (initiating it at age 55 and then engaged in it for 23 y)
the prediction would be that the payback for over 2 decades of
restricting intake would actually only be an extra 6 wk! "

Figure 2 shows that if initiated CR at age 37 (halfway through life),
you only get 30% of its longevity benefits, and the data set is all
over the graph actually.
[/quote]
This study was showed to you, JLC , just to answer to your doubt about
the existence of animal studies under mild CR with a significative
gain of lifespan i.e. 15% CR gives 10% of LS gain
Since you take this opportunity to extract some sentences from the
full text in order to present new reasonings, I will try to reply to
them.

In this article, the mean expectancy for men is 78 and for women is
83; so I don>t know where you get age 37 as the halfway through life

[quote]" Studies of late-onset CR in rodents can allow us to model the impact
of CR protocols initiated in the middle or later in adult life, as
will need to be the case if CR is used in humans. Such modeling
reveals that realistic scenarios of restricting intake by 15â€“30% and
initiating such restriction in one>s 40s will only bring rather small
benefits in extended lifespan despite the CR being extended over
multiple decades. Commencing CR even later, in one>s 60s, may have no
positive effect on life expectan cy. "
[/quote]
"McCay et al (I) postulated that food restriction extends the
life span by slowing growth and delaying development.(...) However,
the concept has been discredited by research findings from our(l0)and
Walfordâ€™s laboratories ( 11). A summary of our results are shown in
Table 1. There was not a significant difference in the age ofthe
10thpercentile survivors between rats in which food restriction (60%
of the ad libitum intake) was initiated at 6 wk of age (2 wk
postweaning) and those in which it was started at 6 mo of age
(young adult life). The maximum life span of these two groups
was almost identical and was much greater than that of the ad
libitum-fed rats." from Masoro http://www.ajcn.org/cgi/reprint/55/6/1250S
Of course, the mean and median LS would have been interesting.
The data are from Yu, Masoro et al: abstract here http://pmid.us/4056321
but no free full text.

[quote]
"In contrast to studies of humans, exercise appears to have only minor
benefits in terms of lifespan in rodents. This may expose a potential
problem extrapolating between rodents and humans because compensatory
consequence of CR may be reduced physical activity. Because rodents
are not unduly troubled by heart disease, they derive little benefit
from elevated exercise but may also be less affected by reduced
exercise. In humans reduced activity in response to CR may lead to
problems with heart health that offset the benefits of CR"
[/quote]
Maybe you miss this in the same full text, "Such a perspective might
be overcautious because the nonhuman primate trials have indicated
that markers of cardiovascular health are significantly improved (66).
Moreover, Fontana et al. (25), studying the voluntary restriction
population, have emphasized the enormous differences in measures of
risks of heart disease relative to the general U.S. population. In
fact, this population has levels of blood pressure typically observed
only in children. " !!!!!!!!!!!

From the same full text "There are, however, some difficulties with
this comparison. If survey responses on the CRON website are
representative, 98% of the CRON population is also regularly
exercising, and the reference group were overweight. The heart health
benefits may therefore derive more from lowered body fat and exercise
than from CR per se."
This is of course related to the impossibility of a double blind
placebo controlled study with humans on CR: see again Roth and al. in
http://pmid.us/16732404

[quote]
"....not yet addressed by CR studies in animals is whether the same
effects will be apparent in humans who have to exist in an environment
where it is necessary to fight off pathogens and perform various
activities beyond sitting in a small room isolated from the external
environment simply to function effectively. "

This 20% calorie restriction down to 2000 calories I would now like to
entitle "FBMCR" or "Faith Based Moderate Calorie Restriction" since it
has little or no support in the literature as being useful for
longevity if started in adult life.
[/quote]
If I understand correctly your reply:
In order to consider the mild CR started in adult life, you>ve taken
the age of 37. So I assume that for you, the adult life begins at
37 !!!!! Anyway, the important matter is really not there:

My main reproach to this paper is, IMO, that it gets the problem from
the wrong side: let>s state this:
From the full text "In humans reduced activity in response to CR may
lead to problems with heart health that offset the benefits of CR"
From this, they infer that the very small benefit from a late CR in
rats should be even more cut "because rodents are not unduly troubled
by heart disease"

In fact, they should have inferred exactly the contrary: since human
health is very sensitive to heart disease, the very small benefit from
a late CR in rodents could probably be transformed in a big (at least
significative) benefit from a late CR in humans and this idea is
supported by this paper from Fontana and al. : http://pmid.us/15096581

"Long-term calorie restriction is highly effective in reducing the
risk for atherosclerosis in humans"
Here long term means 6 years + or - 3 years!!!!!! (yes a mean of 6
years )
"Their average age was 50 Â± 10 years (range 35-82 years)" !!!!

"The CR subjects (...) (minimized) energy content (1,112-1,958 kcal/
day). They eat a wide variety of vegetables, fruits, nuts, dairy
products, egg whites, wheat and soy proteins, and meat (â‰ˆ26% of
calories from protein, â‰ˆ28% from fat, and â‰ˆ46% from complex
carbohydrates). All of CR group strictly avoid processed foods
containing trans fatty acids and high glycemic foods (e.g., refined
carbohydrates, desserts, snacks, and soft drinks). The comparison
group ate typical U.S. diets (...) (1,976-3,537 kcal/day; â‰ˆ18%
calories from protein, â‰ˆ32% from fat, and â‰ˆ50% from carbohydrates)."
"BMI, based on body weight records kept by the participants, decreased
from 24 Â± 3 (range 29.6 to 19.4) kg/m2 to 19.5 Â± 2 (range 22.8 to
16.5) kg/m2 during the period of CR, which averaged 6 Â± 3 years (range
3 to 15 years), with nearly all of the decrease occurring during the
first year. The BMI values for the individuals in the comparison group
were similar to the mean range for middle-aged people in the U.S."
the comparison of the blood parameters between CR and control from the
full text is quite impressive: see http://tinyurl.com/3epk7n
(My personal results of Tchol, LDL, HDL, BP are equals to the CR mean;
my fasting glucose is higher: 93 mg/dl, my TG are lower: 39 mg/dl, my
CRP is lower than 1 (my results don>t give the value!!), my basal
heart beat is 50 (a beat I could never think as reachable for me), I>m
35 and weigh 137 lb)
As you can notice, the BMI of CR people is not very low: 19.5 +/- 2

Another paper from Fontana and al (without free full text so I don>t
know the restriction ratio): http://pmid.us/17389710
"Calorie restriction or exercise: effects on coronary heart disease
risk factors. A randomized, controlled trial."
From the abstract:
"Data from the present study provide evidence that CR-(caloric
restriction) and EX (exercise)-induced negative energy balance result
in substantial and similar improvements in the major risk factors for
CHD (Coronary heart disease) in normal-weight and overweight middle-
aged adults."
"Subjects were 29 women and 17 men aged 57 +/- 3 yr, with BMI 27.3 +/-
2.0 kg/m" (the mean age is 57 !!!!!!!!)
"we conducted a 1-yr controlled trial involving 48 nonobese subjects"
(within only one year !!!!!!!!)
"These CR- and EX-induced energy deficits were accompanied by
reductions in most of the major CHD risk factors, including plasma LDL-
cholesterol, total cholesterol/HDL ratio, HOMA-IR index, and CRP
concentrations that were similar in the two intervention groups"

So when in the first paper we were dealing with (http://pmid.us/
17374682 ) , Speakman and al. state that "when CR is applied in
humans, particular attention should be paid to its impact on physical
activity levels and markers of cardiovascular health", IMO, a
particular attention should be paid to people who are NOT under CR
because people who are not under CR have higher alarm signals of
future cardiovascular issues!!!!
This is also the reason why, I think, that contrary to rodents, humans
should benefit from a mild CR even initiated late in life.

FranÃ§ois Rose

Andrew B. Chung, MD/PhD · Guest

Paul Antonik Wakfer wrote:
[quote]
The following published letter gives a basis for understanding the
evidence that serum glucose spikes are far more harmful than would be
expected merely from their contribution to the total glycation
effects.

---------------- Start of publication ------------------

Free Radic Biol Med. 2008 Jun 1;44(11):1970. Epub 2008 Mar 18.
Deleterious effects due to glucose or to triose phosphates.
Fridovich I.
Department of Biochemistry, Box 3711, Duke University Medical Center,
Durham, NC
27710, USA.
PMID: 18394431

Article

Many of the deleterious consequences of uncontrolled diabetes mellitus
have been attributed to nonenzymatic glycation and such glycation
reactions have been extensively studied [1]. Nakahata et al. [2] have
recently reported that a 15-min exposure of rat brain slices to 20 mM
D-glucose resulted in increased production of superoxide with
decreased arteriolar vasodilation in response to acetylcholine.
Strikingly 20 mM L-glucose was without effect. The nonenzymatic
glycation reaction begins with the coupling of the potential carbonyl
on C-1 of glucose with the amino groups on proteins or nucleic acids.
Since the designations D or L pertain to sterio isomerism at C-5 of
the glucose, it must be expected that D- or L-glucose will participate
in nonenzymatic glycation reactions to the same degree. Moreover
glycation by glucose is a slow reaction and could not have proceeded
significantly in 15 min. It follows that the effects reported by
Nakahata et al. could not have been due to nonenzymatic glycations by
D-glucose.

Glucose exists in solution overwhelmingly in the pyranose form, in
which the carbonyl on C-1 cyclizes by hemiacetal formation with the
hydroxyl on C-5. This masking of the carbonyl explains the slugginess
of nonenzymatic glycation. D-Glucose but not L-glucose can be
converted, by the enzymes of the Embden-Meyerhoff pathway, to triose
phosphates, for which cyclization by hemiacetal formation is not
possible. Hence the triose phosphates are much more prone to
condensation with amino groups than are hexoses such as glucose.
Moreover the triose phosphates can tautomerize to enediols that are
likely to autooxidize with formation of superoxide, hydrogen peroxide,
and diketones [3], [4] and [5]. For these reasons the effects reported
by Nakahata et al. [2] were most probably due to the triose phosphates
derived from D-glucose rather than to D-glucose itself.

A remaining puzzle is why 20 mM glucose was harmful while 5 mM was
not. The rate of entry of D-glucose into the glycolytic pathway is by
way of the hexokinase- or glucokinase-catalyzed phosphorylations.
Hexokinase exhibits a Km for D-glucose of approximately 0.1 mM and is
subject to allosteric inhibition by glucose 6-phosphate. In contrast
glucokinase exhibits a Km for D-glucose of 10 mM and is not inhibited
by glucose 6-phosphate. Thus at 20 mM glucose the glycolytic flux
would not be regulated by the steady-state level of glucose 6-
phosphate, and the formation of the triose phosphates would be higher
than the 5-fold difference in the concentration of the D-glucose
applied by Nakahata et al. [2] It is fortunate that the equilibrium of
the aldolase reaction lies far toward fructose 1,6-bisphosphate. Were
this not the case the concentration of the triose phosphates would be
higher and the deleterious effects of glucose would be apparent even
at the normal 4 mM.
[/quote]
The latter did not happen by fortune but rather by GOD>s design.

We know this because there is no such thing as fortune when everything
that the world would attribute to chance happens by GOD.

"The lot is cast into the lap but its every decision comes from the
LORD." -- King Solomon (Proverbs 16:33)

[quote]References

[1] G. Misciagna, G. De Michelle and M. Trvisan, Nonenzymatic glycated
proteins in the blood and


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