"Anti-Aging" Debates in "SCIENCE" have really started !
Steve Harris
>C'mon, Steve, don't tell us what doesn't
>work, tell us three things that DO work!
>You're a smart scientist and many of us
>(I sure am) are bioinformatic laymen. Tell
>me three more things that do work. I'll
>start with one: statin drugs (not taken at
>the same time as antioxidants). Now tell
>us three more things that work. My life
>hangs in the balance. Post up!
COMMENT:
You got the "drug" for which there's best evidence for life extension (not
the same as anti-aging). The evidence for statins as a life extension pill
is best of all. After that, I would probably put selenium (200 mcg a day) as
the stuff which is mostly likely to help you. Then vitamin E, though
evidence there in human trials is mixed, with the largest trial I know of
showing nada with 20,000 people over 5 years. Possibly aspirin in tiny
doses (40 mg = half a baby aspirin a day) for people over 35 who have ANY
cardiovascular risk factors. And probably aspirin is a good idea for anybody
over 65, though I can't prove this. But I would suggest that even mini-dose
aspirin-takers do frequent stool guaiac tests to make sure they're not
bleeding from the GI tract-- and possibly take Zantac also. CoQ10
supplementation is a good idea if you take a statin. The data for Q10 alone
is mixed, and I tend to be biased because my own experience using it in mice
was very positive. Others haven't been able to generally repeat it, though!
There's some evidence that you'll be sick with infections less often if you
take a good multivitamin, and it's probably good to take folate to keep your
homocysteine levels down (why not? It's cheap).
After that, you're basically down to trying to increase your intake of the
good foods: cold water fish, nuts (except peanuts), and fruits and
vegetables (emphasis on the colored ones). Perhaps a little red wine
nightly, unless you have alcoholism risks or social problems with that. The
epidemiological impact of these foods is vastly greater than than that of
any supplements. Those are the best positives. Epidemiologically the stuff
to stay away from is saturated fat (dairy and most commercial meats), and
all trans fats (diary again, plus anything hydrogenated). Fatwise, besides
fish and nuts, you can eat olives and avocados and a little dark chocolate,
if you like them. And finally, don't get obese no matter what you eat. As
somebody whose BMI right now is 27 and fighting, I can sympathize. But don't
give up. And exercise, even if it's only half an hour a day of brisk
walking; diets for weight loss don't work unless you do.
And hell yes, I take a statin (pravachol), CoQ10, and aspirin and eat all
the fish, nuts, fruit and veggies I can stand. And take my vitamins with V-8
juice at dinner, and have red wine as nightcap. And my dairy fat and trans
fat intake is near zero. But I'd be lying if I said I thought I had any
great answers to life extension that hardly anybody else knows about.
SBH
--
I welcome email from any being clever enough to fix my address. It's open
book. A prize to the first spambot that passes my Turing test.
Chris Malcolm
>You got the "drug" for which there's best evidence for life extension (not
>the same as anti-aging). The evidence for statins as a life extension pill
>is best of all. After that, I would probably put selenium (200 mcg a day) as
>the stuff which is mostly likely to help you. Then vitamin E, though
>evidence there in human trials is mixed, with the largest trial I know of
>showing nada with 20,000 people over 5 years. Possibly aspirin in tiny
>doses (40 mg = half a baby aspirin a day) for people over 35 who have ANY
>cardiovascular risk factors. And probably aspirin is a good idea for anybody
>over 65, though I can't prove this.
You're not worried about the possibly accelerated aging of joints due
to the aspirin?
--
Chris Malcolm c...@dai.ed.ac.uk +44 (0)131 650 3085
School of Artificial Intelligence, Division of Informatics
Edinburgh University, 5 Forrest Hill, Edinburgh, EH1 2QL, UK
[http://www.dai.ed.ac.uk/daidb/people/homes/cam/ ] DoD #205
Steve Harris
>"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> writes:
>
>>You got the "drug" for which there's best evidence for life extension (not
>>the same as anti-aging). The evidence for statins as a life extension pill
>>is best of all. After that, I would probably put selenium (200 mcg a day)
as
>>the stuff which is mostly likely to help you. Then vitamin E, though
>>evidence there in human trials is mixed, with the largest trial I know of
>>showing nada with 20,000 people over 5 years. Possibly aspirin in tiny
>>doses (40 mg = half a baby aspirin a day) for people over 35 who have ANY
>>cardiovascular risk factors. And probably aspirin is a good idea for
anybody
>>over 65, though I can't prove this.
>
>You're not worried about the possibly accelerated aging of joints due
>to the aspirin?
Certainly not at minimal antiplatelet doses. At those doses the aspirin
never even makes it past the liver to the systemic circulation (and thus not
to the joints). Acylation of platelet COX-1 happens while the platelets are
in transit of the portal circulation-- ie, in blood going from gut to
liver. Stomach bleeding effects, if any, will presumably be due *only* to
the lowered platelet function. The standard effects of NSAIDs on COX-1 and
stomach prostaglandins won't be seen, because the dose is simply too low and
stomach COX-1 turnover is too fast in nucleated and dividing cells.
Zar
<sbha...@ix.RETICULATEDOBJECTcom.com> wrote:
> Possibly aspirin in tiny
>doses (40 mg = half a baby aspirin a day) for people over 35 who have ANY
>cardiovascular risk factors. And probably aspirin is a good idea for anybody
>over 65, though I can't prove this. But I would suggest that even mini-dose
>aspirin-takers do frequent stool guaiac tests to make sure they're not
>bleeding from the GI tract-- and possibly take Zantac also.
Is it correct that Zantac will neutralize the acidity of the aspirin?
If so, how do you know that the aspirin will still be effective?
If we wanted to avoid taking the acetyl-salicylic acid, we could
neutralize it *before* we take it. But then it wouldn't be effective.
So why would we want to neutralize it *after* we take it?
Steve Harris
The chemical acidity of aspirin isn't important, and it contributes nothing
to either its effect or its side-effects. For this reason buffered aspirin
isn't any more effective or safe-- even at high doses. It's a non-issue.
For really low doses (such as we're talking about) it's a non-issue squared.
Zantac stops the stomach's acid from being produced-- this lessens stress on
the stomach, and helps small ulcers heal (whereas otherwise, with aspirin,
they may bleed).
Robin
news:agfkum$48r$1...@slb4.atl.mindspring.net...
> You got the "drug" for which there's best evidence for life extension (not
> the same as anti-aging).
What about calorie restriction? ( www.calorierestriction.org and
www.walford.org ) My understanding is that calorie restriction with
adequate nutrition is the only intervention consistently and scientifically
shown to extend life span.
Thomas Carter
Thanks Steve, great answer. I love peanuts. What's wrong with them
other than the fact that they are legumes instead of nuts.?
Thomas
Leonid Gavrilov
>
> >C'mon, Steve, don't tell us what doesn't
> >work, tell us three things that DO work!
> >You're a smart scientist and many of us
> >(I sure am) are bioinformatic laymen. Tell
> >me three more things that do work. I'll
> >start with one: statin drugs (not taken at
> >the same time as antioxidants). Now tell
> >us three more things that work. My life
> >hangs in the balance. Post up!
>
> COMMENT:
>
> You got the "drug" for which there's best evidence for life extension (not
> the same as anti-aging). The evidence for statins as a life extension pill
> And hell yes, I take a statin (pravachol>..
SBH
"PravacholŽ, a prescription drug, is not for everyone, including women
who are pregnant or nursing or may become pregnant, or people with
liver problems. And because serious side effects can result, patients
should tell their doctor about any unexplained muscle pain or weakness
they experience while on PravacholŽ, and about any other medications
they are taking. It is recommended that liver function tests be
performed prior to initiating therapy, prior to increasing the dose,
and when otherwise clinically indicated. The combined use of
pravastatin and fibrates should be avoided unless the benefit on lipid
levels is likely to outweigh the increased risk of this drug
combination. Some mild side effects, such as slight rash or stomach
upset, occurred in 2-4% of patients."
http://www.bms.se/heart_lakare/pravachol.htm
"Side effects may include impotence; muscle aches; pain tenderness or
weakness; numbness or tingling; headache and vomiting."
http://www.med.umich.edu/1libr/prescrpt/choles03.htm
"You should not take Pravachol if you are allergic to Lovastatin
(loe-vah-STAT-in). Be sure to consult your doctor before starting the
medication if you take immunosuppressive drugs, particularly following
a heart transplant. Also, do not take if you have low blood pressure,
if you have hormone abnormalities, if you have an active infection or
if you have a liver disease. While on Pravachol avoid a high-fat diet
or taking other medicine without consulting your physician. You should
inform the doctor before starting if you are pregnant, breast-feeding,
or plan to become pregnant, or are over age 60. Blood tests to monitor
cholesterol levels will need to be taken periodically while usingthis
drug."
http://www.med.umich.edu/1libr/prescrpt/choles03.htm
"Gaist, a neurologist at Odense University Hospital, Denmark, has
linked statin use to seven cases of polyneuropathy. This led him to do
a larger study of all first-time cases of this unusual nerve damage
treated in Denmark. He found that people who took statins for two or
more years had more than a 26-fold increase in polyneuropathy. Some
patients' symptoms did not get better even a year after stopping the
drugs.
The report appears in the May issue of Neurology.
These findings don't surprise Beatrice A. Golomb, MD, PhD. Golomb
leads two ongoing studies of statin side effects at the University of
California, San Diego.
"This is one of the top three complaints we hear most commonly from
people taking statins: muscle problems, [thinking] problems, and
neuropathy," Golomb tells WebMD. "We are surprised more attention
hasn't been paid to this."
http://webmd.lycos.com/content/article/1809.51585
Hope this helps to be cautious. Best wishes,
Leonid Gavrilov
______________________________________
Dr. Leonid A. Gavrilov, Center on Aging
NORC/University of Chicago
1155 East 60th Street
Chicago, IL 60637-2745
USA
Fax: (773) 256-6313, Phone: (773) 256-6359
FOR MORE INFO PLEASE VISIT OUR SCIENTIFIC WEBSITE :
http://www.src.uchicago.edu/~gavr1/
John 'the Man'
rambled on about "Re: "Anti-Aging" Debates in "SCIENCE" have really
started !."
Our champion De-Medicalizing in sci.med.nutrition retorts, thusly ...
>> Possibly aspirin in tiny
>>doses (40 mg = half a baby aspirin a day) for people over 35 who have ANY
>>cardiovascular risk factors. And probably aspirin is a good idea for anybody
>>over 65, though I can't prove this. But I would suggest that even mini-dose
>>aspirin-takers do frequent stool guaiac tests to make sure they're not
>>bleeding from the GI tract--
I took 3 adult size 325 mg aspirins before bed for several years
because of dental headaches.
Never had a stomach problem. Never had heart burn or an ulcer. :-)
I have a cast iron stomach.
The dental headaches are gone, and I don't take anymore aspirin. I
wonder why?
Ha, ... Hah, Ha!
--
John Gohde,
Achieving good Health is an Art, NOT a Science!
http://NaturalHealthPerspective.com/
The ONLY Frauds in Health are those who couldn't care less about
prevention. Beware of anybody who brags about eating a lousy diet,
being overweight, or about smoking!
JEDilworth
See this recent article. It cites NIH research. Women have to maintain a
calorie intake of 1120 calories/day, and a man only 1540 calories/day.
There's not a lot of wiggle room.
Judy Dilworth, M.T. (ASCP)
Microbiology
jril...@bigpond.net.au
<DeMan[72]@hotmail.com> wrote:
>Once upon a time, our fellow Zar
> rambled on about "Re: "Anti-Aging" Debates in "SCIENCE" have really
>started !."
>Our champion De-Medicalizing in sci.med.nutrition retorts, thusly ...
>
>>> Possibly aspirin in tiny
>>>doses (40 mg = half a baby aspirin a day) for people over 35 who have ANY
>>>cardiovascular risk factors. And probably aspirin is a good idea for anybody
>>>over 65, though I can't prove this. But I would suggest that even mini-dose
>>>aspirin-takers do frequent stool guaiac tests to make sure they're not
>>>bleeding from the GI tract--
>
>I took 3 adult size 325 mg aspirins before bed for several years
>because of dental headaches.
>
>Never had a stomach problem. Never had heart burn or an ulcer. :-)
>
>I have a cast iron stomach.
>
>The dental headaches are gone, and I don't take anymore aspirin. I
>wonder why?
>
>Ha, ... Hah, Ha!
You probably had bleeds, but didn't notice them. Did you test?
Most folk have small bleeds from a 600mg dose of aspirin.
jl
Steve Harris
>Thanks Steve, great answer. I love peanuts. What's wrong with them
>other than the fact that they are legumes instead of nuts.?
>Thomas
Peanut oil is atherogenic.
Keith F. Lynch
> Zantac stops the stomach's acid from being produced-- this lessens
> stress on the stomach, and helps small ulcers heal (whereas
> otherwise, with aspirin, they may bleed).
Doesn't stomach acid have some important function? If not, why does
the body produce it?
I can understand blocking it if there's a serious medical problem
which it contributes to. But it seems strange to say that almost
everyone should take aspirin, and that everyone who takes aspririn
should take Zantac.
--
Keith F. Lynch - k...@keithlynch.net - http://keithlynch.net/
I always welcome replies to my e-mail, postings, and web pages, but
unsolicited bulk e-mail (spam) is not acceptable. Please do not send me
HTML, "rich text," or attachments, as all such email is discarded unread.
jril...@bigpond.net.au
wrote:
>Steve Harris <sbha...@ix.RETICULATEDOBJECTcom.com> wrote:
>> Zantac stops the stomach's acid from being produced-- this lessens
>> stress on the stomach, and helps small ulcers heal (whereas
>> otherwise, with aspirin, they may bleed).
>
>Doesn't stomach acid have some important function? If not, why does
>the body produce it?
To kill things that have been swallowed whole :)
>I can understand blocking it if there's a serious medical problem
>which it contributes to. But it seems strange to say that almost
>everyone should take aspirin, and that everyone who takes aspririn
>should take Zantac.
I take ~100mg aspirin per day on a full stomach and have no
discernable ill effects. I buy the cheapest generic soluble aspirin
and break them in three.
I wouldn't have thought Zantac (H2 inhibitor) should be taken by
anyone without symptoms.
jl
Paul Rogers
<sbha...@ix.RETICULATEDOBJECTcom.com> wrote:
>. . .and it's probably good to take folate to keep your
>homocysteine levels down (why not? It's cheap).
. . . for cancer prevention as well as cardiovascular disease.
PR
Alex Brands
>
> I took 3 adult size 325 mg aspirins before bed for several years
> because of dental headaches.
>
> Never had a stomach problem. Never had heart burn or an ulcer. :-)
>
> I have a cast iron stomach.
>
> The dental headaches are gone, and I don't take anymore aspirin. I
> wonder why?
Because all your teeth fell out?
Alex Brands
> Thomas Carter wrote in message ...
>
> >Thanks Steve, great answer. I love peanuts. What's wrong with them
> >other than the fact that they are legumes instead of nuts.?
> >Thomas
>
> Peanut oil is atherogenic.
There's also the aflatoxin problem.
Peanuts are prone to be contaminated with a fungus that makes something
called aflatoxin which seems to increase one's risk for liver cancer.
Brynjulf Barexstein
> > Peanut oil is atherogenic.
This made me curious. I almost "live" on peanuts and peanut products,
believing it is one of the most healthy foodstuff you can find !
From where have you got this information ?
Peanut oil is polyunsaturated, so what is wrong with it ?
Dr B.Barexstein, M.D.
Dwight Hooper
If you do a Google Groups search of the nutrition group, you will find
Tom M. referencing Lipid 1998; 33(8): 821-3
The lectins in the peanut oil and the peanuts seem to contribute to
the aforemention problem. I recall John G. referred to this last month
though he got the details confused:-)
All I know is that roasted peanuts tend to cause me "heartburn" though
raw peanuts and other raw nuts don't.
DH..... the lurker
"Brynjulf Barexstein" <br...@online.no> wrote in message news:<plGX8.4931$HR.6...@news4.ulv.nextra.no>...
Alex Brands
It's not the fat itself, it's some other compound in the oil.
There used to be this notion that it was the arrangement of the fatty
acids on the glycerol backbone. Some chemist removed the fatty acids,
then put them back in random arrangements, and the oil was no longer
atherogenic. He concluded that it was the arrangement of the fatty
acids causing the problem. It turns out that during those manipulations
he was inadvertently purifying the oil of the responsible compound.
Alex
Thomas Carter
Thx to Steve and George for motavating me to study this issue.
Numbers in () refer to the abstracts below.
Peanut oil is undeniably atherogenic in rabbits which can not clear
dietary cholesterol from their blood and are therefore used as models
for the study of arterial disease. (1), (7), (9), (10), (11) The
action is clearly accelerated greatly by very high, non-physiological
doses of cholesterol. With the lower doses the results are mixed. The
only human study (12), and a newer primate study indicates a benefit.
(13) The human study is an epidemiological mega study on nuts, so the
peanut effect is surely swamped by other foods. Although the fatty
acid profile of peanuts is good, the bad fats are on the outside of
the glycerol molecule and the linoleic molecule is sandwiched in the
middle and thus less bioavailable, (2), (3) perhaps more importantly
peanuts contain lectins which are proteins that contribute to the
stickiness of RBC's and other cells and are clearly atherogenic. (4),
(5) The atherogenic action of lectins could be quite slow and thus
catch humans at an advanced age, since it may cause soft tissue
calcification (6) Based on the CVD evidence alone I think it could be
a tough decision whether to eat them or not. I would probably not
since there are other good options. The cancer evidence OTOH is
clearly bad, alarming, and significant . GST-M1 and GSTT1 are
polymorphic enzymes possessed homozygously by half of the US
Caucasians. The liver of people who are null for these allels can not
clear toxins well from their blood. They may increase the risk of
liver cancer by up to 1600% in the top quartile of peanut intake.(14)
Hi risk is also incurred at other sites such as the lung(15), (16).
People who sunburn easily are much more likely to carry the GST genes
(17). These people may also be more susceptible to atherogenesis due
to peanuts. (16)
(1) Int J Tissue React 1991;13(2):59-65 Dietary fat and experimental
atherosclerosis. Kritchevsky D. Wistar Institute of Anatomy and
Biology, Philadelphia, Pennsylvania 19104. This paper reviews studies
relating to the effects of fat unsaturation and fatty acid composition
on the development of experimental atherosclerosis in rabbits. The
results derived from the feeding of various fats are similar whether
one feeds cholesterol or an atherogenic, cholesterol-free semipurified
diet. In general, the severity of atherosclerosis is inversely related
to the level of fat unsaturation. Two exceptions are cocoa butter
which is much less atherogenic than expected, most probably due to its
high content of stearic acid, and peanut oil, while relatively
unsaturated, is surprisingly atherogenic for rats, rabbits and
monkeys. This latter effect is not related to the level (6%) of
long-chain saturated fatty acids (arachidic, behenic, lignoceric)
present in peanut oil, but rather to its triglyceride structure.
Randomization of peanut oil, which modifies its triglyceride
structure, significantly reduces its atherogenicity. Publication
Types: Review Review, Tutorial PMID: 1955294
………………………………..
(2). Randomization (a process in which the fatty acids in peanut oil
are randomly rearranged)
of peanut oil reduces its atherogenicity, suggesting that the
structure of the triglyceride comprising peanut oil may affect its
atherogenic potential. Another possibility is that a lectin present in
peanut oil may be responsible for its atherogenic capacity.
Publication Types: Review Review, Tutorial PMID: 3052354
……………………………..
(3) Lipids 1977 Oct;12(10):775-85 Acylglycerol structure of peanut
oils of different atherogenic potential. Myher JJ, Marai L, Kuksis A.
Detailed investigation was made of the triacylglycerol structure of
native, simulated, and interesterified peanut oils, which had
previously been shown to differ markedly in their atherogenic
potential. By means of chromatographic and stereospecific analyses, it
was shown that the more atherogenic native oil contains a
significantly greater proportion of triacylglycerols with linoleic in
sn-2-position and arachidic, behenic, and lignoceric acids in
sn-3-position that the synthetic oils. It is suggested that the
atherogenicity may arise from a relative metabolic unavailability of
the linoleic acid from the native oil, which may be due in part to the
presence of long chain saturated acids in the outer position. This
might render the oil metabolically more saturated that the
interesterified oils of the same total fatty acid composition, which
contain a much greater proportion of the linoleic acid in the primary
postions of the triacylglycerol molecule. The identification of
specific triacylglycerols may allow the experimental testing of this
hypothesis by feeding synthetic triacylglycerols incorporating the
potentially atherogenic features. PMID: 916819
………………………
(4) Lipids 1987 Sep;22(9):667-8 Isolation and quantitation of lectins
from vegetable oils. Klurfeld DM, Kritchevsky D. Wistar Institute,
Philadelphia, PA 19104. The factor(s) responsible for the unexplained
atherogenicity of peanut oil remain to be elucidated. To this end, we
developed a technique to determine if lectin was present in the oil
and to quantitate its concentration. This technique was applied to
other vegetable oils including corn, soybean, and sunflower. Crude,
unprocessed corn and soybean oils were also analyzed for lectin
content. The crude oils contained from 858 to 2983 micrograms lectin
per kg, while the refined oils contained 24 to 55 micrograms/kg of
biologically active lectin. The identities of the isolated lectins
were confirmed by electrophoresis on SDS-polyacrylamide gels. The
biological significance of the presence of lectin in these oils
remains to be determined. PMID: 3669929
lectin
<plant biology> Proteins obtained particularly from the seeds of
leguminous plants, but also from many other plant and animal sources,
that have binding sites for specific mono or oligosaccharides in cell
walls or membranes. They thereby change the physiology of the membrane
to cause agglutination, (agglutin proteins on the cell membrane cause
cells to clump together) mitosis, or other biochemical changes in the
cell.
Named originally for the ability of some to selectively agglutinate
human red blood cells of particular blood groups. Lectins such as
concanavalin A and wheat germ agglutinin are widely used as analytical
and preparative agents in the study of glycoproteins.
(5) Lipids 1998 Aug;33(8):821-3 Lectin may contribute to the
atherogenicity of peanut oil. Kritchevsky D, Tepper SA, Klurfeld DM.
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
kritc...@wista.wistar.upenn.edu Peanut oil is unexpectedly
atherogenic for rats, rabbits, and primates. The lesions it produces
are more fibrous than fatty. The mechanism underlying the
atherogenicity of peanut oil has been elusive. Randomization of peanut
oil reduces significantly its atherogenic properties, but native and
randomized peanut oils have similar rates of lipolysis, and rats fed
the two oils absorb and transport lipids in a similar fashion. Peanut
oil differs from other oils in having a relatively high lectin
content, and the randomization process markedly reduces the lectin
content as well. The biologically active lectin of peanut oil has an
affinity for glycoproteins found specifically on arterial smooth
muscle cells. Peanut lectin has been shown to stimulate growth of
smooth muscle and pulmonary arterial cells. Vigorous washing of peanut
oil reduces its lectin content by 46%. Compared to rabbits fed
cholesterol and peanut oil, rabbits fed cholesterol and washed peanut
oil exhibited less severe atherosclerosis in the aortic arch (by 9%)
and in the thoracic aorta (by 31%). The data suggest that peanut oils'
endogenous lectin may contribute significantly to its atherogenic
properties. PMID: 9727614
………………………………….
(6) Biochim Biophys Acta 2000 Apr 5;1464(2):262-72 Effects of lectins
on calcification by vesicles (A closed membrane shell, derived from
membranes either by a physiological process (budding) or mechanically
by sonication.Vesicles of dimensions in excess of 50nm are believed to
be important in intracellular transport processes.) isolated from
aortas of cholesterol-fed rabbits. Hsu HH, Tawfik O, Sun F. Department
of Pathology and Laboratory Medicine, University of Kansas Medical
Center, Kansas City, KS 66160-7410, USA. hh...@kumc.com Advanced
vascular calcification in atherosclerosis weakens arterial walls,
thereby imposing a serious rupturing effect. However, the mechanism of
dystrophic calcification remains unknown. Although accumulating
morphological and biochemical evidence reveals a role for calcifiable
vesicles in plaque calcification, the mechanism of vesicle-mediated
calcification has not been fully explored. To study whether vesicles'
membrane components, such as carbohydrates, may have a role in
vesicle-mediated calcification, the effect of sugar-binding lectins on
calcification was investigated. Atherosclerosis was developed by
feeding rabbits with a diet supplemented with 0.5% cholesterol and 2%
peanut oil for 4 months. Calcifiable vesicles were then isolated from
thoracic aortas by collagenase digestion. The histological examination
of aortas with hematoxylin counter-staining indicated abnormal
formation of large plaques enriched with macrophage-derived foam
cells. Fourier transform spectroscopy revealed mild calcification in
aortas indicating that advanced stages of heavy calcification have yet
to be reached. However, vesicles isolated from the aortas were capable
of calcification in the presence of physiological levels of Ca(2+),
Pi, and ATP. Thus, at this stage of atherosclerosis, aortas may start
to produce calcifiable vesicles, but at a level insufficient for
substantial formation of mineral in aortas. The assessments by FT-IR
analysis and Alizarin red staining indicated that concanavalin A (Con
A) substantially increased mineral formation by isolated vesicles. Con
A also exerted a marked stimulatory effect on (45)Ca and (32)Pi
deposition in a dose-dependent fashion with a half-maximal effect at
6-10 microg/ml. Either alpha-methylmannoside or alpha-methylglucoside,
but not mannitol, at 10 mM abolished the stimulation. Con A
stimulation was abolished after Con A was removed from calcifying
media, suggesting that covalent binding may not be involved in the
effect. Galactosides appear to also be implicated in (45)Ca and (32)Pi
deposition since Abrus precartorius agglutinin, which specifically
binds galactosides, enhanced the deposition. Neither wheat-germ
agglutinin that binds N-acetylglucoside nor
N-acetylgalactoside-specific Helix pomatia agglutinin was effective,
suggesting that the acetylated forms of carbohydrate moieties are
either absent in vesicles or may not be involved in calcification.
None of these lectins exerted an effect on ATPase. Thus, the effects
of lectins appeared to be mediated through interactions with
carbohydrate moieties of calcifiable vesicles. Whether stimulation of
vesicle-calcification by lectins is of pathological significance in
atherosclerotic calcification requires further investigation. PMID:
10727613 …………….
(7) J Vet Med Sci 1994 Feb;56(1):83-9 Comparison of atherogenicity of
soybean oil and peanut oil, and effect of clentiazem on diet-induced
atherosclerosis in rabbits. Saso Y, Iwasaki H, Yasoshima A, Takashima
K, Morita T. Pharmacological Research Laboratory, Tanabe Seiyaku Co.,
Ltd., Saitama, Japan. Rabbits were fed with two kinds of atherogenic
diet, one containing 0.5% cholesterol and 3% soybean oil and the other
0.5% cholesterol and 6% peanut oil, for three months to compare the
atherogenic property of the diets. The soybean oil diet seemed to be
superior to the peanut oil diet for evaluation of the anti-atherogenic
effect of drugs, because the former caused milder vascular lesions
than the latter. Using this rabbit model for atherosclerosis, the
anti-atherogenic effect of clentiazem, a new calcium antagonist, was
examined. Clentiazem at an oral dose of 30 mg/kg/day significantly
reduced the size of atheromatous lesion in the aortic arch and
thoracic aorta, and lowered the collagen content of the aortic intima
and media, although it did not decrease serum lipid levels. On the
other hand, clentiazem showed no clear effect on reducing the coronary
atherosclerotic lesions. These results suggest that clentiazem may
inhibit the progression of diet-induced aortic atherosclerosis without
normalizing the serum lipid levels. PMID: 8204766
…………………..
(8) Atherosclerosis 1981 Feb-Mar;38(3-4):291-9 Cholesterol vehicle in
experimental atherosclerosis. Part 18. Comparison of North American,
African and South American peanut oils. Kritchevsky D, Tepper SA,
Scott DA, Klurfeld DM, Vesselinovitch D, Wissler RW. Peanut oils were
obtained from the United States (NAPNO), Africa (APNO), and South
America (SAPNO) and their effects on atherosclerosis in rabbits fed 2%
cholesterol were determined. The major differences among the oils were
in the content of oleic (NAPNO, 48.9%; APNO, 58.6%; SAPNO, 36.4%) and
linoleic (NAPNO, 29.6%; APNO, 21.7%; SAPNO, 41.1%) acids. In a series
of 4 experiments it was found that South American peanut oil was 7%
more atherogenic than African peanut oil and 18% more atherogenic than
North American peanut oil. American peanut oil was 14% more
atherogenic that corn oil (CO). South American peanut oil gave highest
serum and liver lipid levels. The differences in atherogenicity may be
due to the structure of the triglycerides of the various peanut oils.
PMID: 7225168 …………………………………
(9) Atherosclerosis 1978 Nov;31(3):365-70 Cholesterol vehicle in
experimental atherosclerosis. Part 16. Effect of peanut oil on
pre-established lesions. Kritchevsky D, Tepper SA, Story JA. Rabbits
were fed an atherogenic diet (2% cholesterol and 6% corn oil) for 8
weeks and then divided into groups of equal average serum cholesterol
levels. One group was autopsied, and the others were returned to
cholesterol-free diets consisting of commercial laboratory ration or
ration augmented with 6% corn oil, peanut oil or PGF, a fat designed
to resemble peanut oil minus arachidic and behenic acids. The animals
were maintained on the diets for 8 more weeks. On all regimens,
severity of atherosclerosis was exacerbated. The extent of
exacerbation was significantly less in rabbits fed corn oil than in
the others. The extent of exacerbation of lesions appears to be a
function of the level of unsaturation of the dietary fats. PMID:
718739……………..
The greatest prevalence of myocardial infarcts was found in rhesus
monkeys fed a cholesterol-containing diet with 40% of calories
supplied by peanut oil and in cynomolgus macaques from Malaya that
were fed the same amount of cholesterol with 40% of calories from
lard. Electrocardiographic abnormalities as well as the occurrence of
unexpected and relatively sudden death in several of these nonhuman
primates are also consistent with signs frequently observed in human
beings.PMID: 7446712………………………..
(10) Atherosclerosis 1984 Mar;50(3):253-9 Experimental
atherosclerosis in rabbits fed cholesterol-free diets. Part 12.
Comparison of peanut and olive oils. Kritchevsky D, Tepper SA,
Klurfeld DM, Vesselinovitch D, Wissler RW. The atherogenicity of
peanut oil is well established as is the fact that the structure of
the component triglycerides of peanut oil influences its
atherogenicity. This study was carried out to determine if the
relative saturation of peanut oil was partly responsible for the
observed effects. Rabbits were fed a semipurified, cholesterol-free
diet containing 14% of North American peanut oil (iodine value, 100),
South American peanut oil (iodine value, 110) or olive oil (iodine
value, 83) for 8 months. Rabbits fed olive oil exhibited higher levels
of serum and liver lipids than did the two peanut oil-fed groups but
significantly lower levels of aortic atherosclerosis. The findings
confirm earlier observations that the structure of a fat can have an
affect on its atherosclerogenic potential that is independent of its
level of unsaturation. PMID: 6324825
…………………………………..
(11) Arterioscler Thromb Vasc Biol 1996 Dec;16(12):1454-64
Hypercholesterolemia in the rabbit induced by feeding graded amounts
of low-level cholesterol. Methodological considerations regarding
individual variability in response to dietary cholesterol and
development of lesion type. Kolodgie FD, Katocs AS Jr, Largis EE,
Wrenn SM, Cornhill JF, Herderick EE, Lee SJ, Virmani R. Department of
Cardiovascular Pathology, Armed Forces Institute of Pathology,
Washington, DC 20306-6000, USA. While a number of studies have
presented detailed examinations of lesion development in the
cholesterol-fed rabbit, individual variability in response to
cholesterol feeding and type of lesion produced relative to the degree
of cholesterol exposure is not well defined. This study analyzed such
critical parameters in an attempt to further characterize the model
and establish a baseline for future testing of treatments targeted at
limiting atherosclerosis. For these experiments, male New Zealand
White rabbits were fed atherogenic diets consisting of 0.05%, 0.10%,
0.15%, 0.20%, or 0.25% cholesterol dissolved in 6% peanut oil for 31
to 32 weeks. Raising dietary cholesterol from 0.05% to 0.15% resulted
in a less than twofold stepwise increase in total plasma cholesterol
(TPC) exposure (area under plasma cholesterol versus time curve),
whereas further increases in cholesterol intake resulted in an
exponential four- to fivefold increase in TPC exposure. (I get much
less than .05% cholesterol) Regression analysis of TPC exposure with
aortic sudanophilia demonstrated a threshold of approximately 5000
cholesterol weeks; below this limit lesions were minimal, and above
this value the degree of plaque correlated with TPC exposure.
Furthermore, a wide biological variability occurred among rabbits with
respect to individual responsiveness to dietary cholesterol. In the
aorta, various types of plaques, from fatty streaks to atheromatous
lesions, were observed, depending on the degree of cholesterol intake.
Diets consisting of < 0.15% cholesterol resulted in the development of
fatty streak lesions, while transitional lesions and atheromatous
plaques were mostly found with higher cholesterol feeding. Coronary
artery atherosclerosis was present in > 50% of animals fed diets > or
= 0.15% cholesterol. Despite the level of TPC exposure, coronary
lesions in epicardial vessels were generally the fibrous type, whereas
intramyocardial arteries demonstrated predominantly intimal foam
cells. In conclusion, by adjusting dietary cholesterol intake and
selecting rabbits with a similar responsiveness to cholesterol, the
overall cholesterol exposure can be more closely controlled to
minimize the inherent individual variability among animals in this
model. The nature of the target lesion must also be carefully
considered, because the efficacy of some treatments may depend on the
type of atherosclerotic plaque. PMID: 8977449 Full text available
…………………………
(12) Curr Atheroscler Rep 1999 Nov;1(3):204-9 Nut consumption and risk
of coronary heart disease: a review of epidemiologic evidence. Hu FB,
Stampfer MJ. Department of Nutrition, Harvard School of Public Health,
665 Huntington Avenue, Boston, MA 02115, USA. Traditionally nuts have
been perceived as an unhealthy food because of their high fat content.
However, recent accumulative evidence suggests that frequent
consumption of nuts may be protective against coronary heart disease
(CHD). So far, five large prospective cohort studies (the Adventist
Health Study, the Iowa Women Health Study, the Nurses' Health Study,
the Physicians' Health Study, and the CARE Study) have examined the
relation between nut consumption and the risk of CHD and all have
found an inverse association. In addition, several clinical studies
have observed beneficial effects of diets high in nuts (including
walnuts, peanuts, almonds, and other nuts) on blood lipids. The
beneficial effects of nut consumption observed in clinical and
epidemiologic studies underscore the importance of distinguishing
different types of fat. Most fats in nuts are mono- and
polyunsaturated fats that lower low-density lipoprotein cholesterol
level. Based on the data from the Nurses' Health Study, we estimated
that substitution of the fat from 1 ounce of nuts for equivalent
energy from carbohydrate in an average diet was associated with a 30%
reduction in CHD risk and the substitution of nut fat for saturated
fat was associated with 45% reduction in risk. Given the strong
scientific evidence for the beneficial effects of nuts, it seems
justifiable to move nuts to a more prominent place in the United
States Department of Agriculture Food Guide Pyramid. Regular nut
consumption can be recommended in the context of a healthy and
balanced diet. Publication Types: Meta-Analysis PMID: 11122711
………………………..
(13) Arteriosclerosis 1986 Sep-Oct;6(5):465-74 Peanut oil reduces
diet-induced atherosclerosis in cynomolgus monkeys. Alderson LM, Hayes
KC, Nicolosi RJ. The atherogenicity of dietary peanut oil (PO) was
examined in cynomolgus monkeys fed semipurified diets for 15 months.
Four groups of six monkeys were fed diets containing 0.22 mg/kcal
(0.1%) cholesterol and 0%, 5%, 10%, or 20% PO. An additional group was
fed 2.0% cholesterol and 20% PO to serve as a literature control.
Increasing the concentration of PO in the diet was associated with
significant decreases in total plasma cholesterol (p less than 0.05)
and the total/HDL cholesterol ratio (p less than 0.05) and an increase
in the terminal HDL cholesterol concentration (p less than 0.05).
Intimal thickness and composition were determined from cross sections
of the thoracic aorta and the iliac and coronary arteries. Increasing
dietary PO was associated with decreases in thickness (p less than
0.005), lipid (p less than 0.001), and smooth muscle cells (p less
than 0.005) in the aortic intima. Aortic intimal lipid was positively
correlated with the ratio of total to HDL cholesterol (r2 = 0.78, p
less than 0.05). Monkeys fed 2.0% cholesterol and 20% PO revealed
extensive atherosclerosis in all three arterial sites compared with
those of any other group. Whereas the dietary fat effect was most
demonstrable in the aorta, dietary cholesterol had a greater effect on
the iliac and coronary arteries than it did on the aorta. Under these
circumstances, dietary PO was not atherogenic in cynomolgus monkeys
when fed with a concentration of cholesterol equivalent to that
consumed by humans. PMID: 3767691
…………………..
(14) Cancer Causes Control 2001 Jan;12(1):23-32 Peanut butter intake,
GSTM1 genotype and hepatocellular carcinoma: a case-control study in
Sudan. Omer RE, Verhoef L, Van't Veer P, Idris MO, Kadaru AM, Kampman
E, Bunschoten A, Kok FJ. Department of Crop Protection, Faculty of
Agriculture, University of Khartoum, Sudan. raja...@usa.net
OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the major cancers
in the world. In Sudan the incidence is thought to be high and
increasing. This study aims to assess the association between peanut
butter intake, as a source of aflatoxins, and the GSTM1 genotype in
the etiology of HCC. METHOD: A case control study was conducted among
150 patients and 205 controls from two regions in Sudan. Food habits
with special reference to peanut butter consumption, as well as peanut
storage systems, have been investigated, as well as confounders such
as hepatitis, drinking and smoking habits, and demographic
characteristics. GSTM1 genotype was assessed in DNA extracted from
blood samples (110 cases, 189 controls). RESULTS: A positive
association was observed for highest vs. lowest quartile of peanut
butter intake, humid storage system and HCC, with ORs (95% CI) being
3.0 (1.6-5.5) and 1.6 (1.1-2.5) respectively. The positive association
with peanut butter intake was essentially limited to subjects with
GSTM1 null genotype with OR for highest vs. lowest quartile 16.7
(2.7-105). CONCLUSION: Peanut butter consumption has been identified
as a strong risk factor of HCC in a region with endemic aflatoxin
contamination in Sudan and was essentially limited to subjects with
the GSTM1 null genotype. PMID: 11227922
……………………..
(15) Cancer Epidemiol Biomarkers Prev 1997 Sep;6(9):733-43 Molecular
epidemiology of the human glutathione S-transferase genotypes GSTM1
and GSTT1 in cancer susceptibility. Rebbeck TR. Department of
Biostatistics and Epidemiology, University of Pennsylvania, School of
Medicine, Philadelphia 19104-6021, USA. reb...@cceb.med.upenn.edu The
mu (GSTM1 and theta (GSTT1) members of the glutathione S-transferase
multigene family are candidate cancer susceptibility genes because of
their ability to regulate the conjugation of carcinogenic compounds to
excretable hydrophilic metabolites. Deletion variants that are
associated with a lack of enzyme function exist at both these loci.
Individuals who are carriers of homozygous deletions in the GSTM1 of
GSTT1 genes may have an impaired ability to metabolically eliminate
carcinogenic compounds and may therefore be at increased cancer risk.
Molecular epidemiological studies have provided three pieces of
information about the relationship of GSTM1 and GSTT1 with cancer
susceptibility. First, the frequencies of homozygous GSTM1 and GSTT1
deletion carriers is very high (i.e., 20-50%) in most populations
studied to date. Second, GSTM1 and, possibly, GSTT1 may be involved in
the etiology of cancer at more than one site. Third, the risk
conferred to individuals who carry homozygous deletions in GSTM1 and
GSTT1 appears to be small in magnitude. (e.g., odds ration of < 2).
However, the magnitude of risk is larger (e.g., odds ratio of 3-5)
when interactions of GSTM1 of GSTT1 with other factors (e.g.,
cigarette smoking) are considered. These findings have implications
for studies of GSTM1 and GSTT1 in cancer susceptibility and for future
applications of these biomarkers in cancer prevention of control
strategies. First, molecular epidemiological studies should consider
both the common frequency of deletion genotypes and the relatively low
cancer risk these deletion genotypes may impart. For example, the
common frequency of deletion variants may improve statistical power in
some molecular epidemiological studies, but large samples may still be
required to detect relatively small effect sizes or important
interaction effects. Second, the fact that deletion genotypes are
common implies that the proportion of cancer attributable to these
variants may be large in the general population. However, these
genotypes may be less suited for individual cancer risk assessment
because of their relatively small contribution to the absolute risk of
cancer. Publication Types: Review Review, Academic PMID: 9298582
…………………………..
(16) Mutat Res 2001 Sep 1;480-481:9-22 Multiple points of intervention
in the prevention of cancer and other mutation-related diseases. De
Flora S, Izzotti A, D'Agostini F, Balansky RM, Noonan D, Albini A.
Department of Health Sciences, University of Genoa, Genoa, Italy.
s...@unige.it Multiple points of intervention are the target for
dietary and pharmacological interventions aimed at preventing cancer
and other diseases in which mutations in somatic cells play a
pathogenetic role. For instance, our studies showed that DNA adducts
can be consistently detected in arterial smooth muscle cells from
human atherosclerotic lesions. Their levels were significantly
correlated with the occurrence of atherogenic risk factors known from
traditional epidemiology and were strikingly enhanced in
atherosclerotic patients lacking the GSTM1 genotype. Cancer
chemoprevention has a dual goal, i.e. prevention of occurrence of the
disease (primary prevention) and early detection and reversion of
tumors at a premalignant stage (secondary prevention). At a later
stage, attempts can be made to prevent local recurrences as well as
invasion and metastasis of malignant cells (tertiary prevention). For
a rational use of chemopreventive agents it is essential not only to
evaluate their efficacy and safety but also to understand the
mechanisms involved. Sometimes it is difficult to discriminate whether
modulation of a given end-point is actually a specific mechanism or
rather the epiphenomenon of other events. For instance, we recently
found that apoptosis is considerably stimulated in the respiratory
tract of smoke-exposed rats; whereas certain chemopreventive agents
work by further enhancing smoke-related apoptosis, other agents appear
to downregulate apoptosis simply because they inhibit the genotoxic
events signaling this process. We propose here a detailed, updated
classification of the points of intervention exploitable in the
prevention of mutation and cancer. The general outline includes a
variety of extracellular and cellular mechanisms modulating the
genotoxic response and tumor initiation as well as tumor promotion,
progression, angiogenesis, invasion, and metastasis. This
classification is not intended to provide a rigid scheme, since
several intervention points are reiterated several times over
different phases of the process. Moreover, some mechanisms are
strictly interconnected or partially overlapping. Interestingly, a
number of chemopreventive agents work through multiple mechanisms,
which warrants a higher efficacy and a broader spectrum of action. It
is also convenient to combine chemopreventive agents working through
complementary mechanisms. In recent preclinical studies, we observed
that combination of N-acetylcysteine with either oltipraz or ascorbic
acid produces additive or more than additive protective effects
towards early biomarkers and/or experimentally-induced tumors.
Publication Types: Review Review, Tutorial PMID:
11506795……………………………
(17) Am J Pharmacogenomics 2002;2(2):147-54 Influence of GSTT1 and
GSTM1 Genotypes on Sunburn Sensitivity. Kerb R, Brockmoller J,
Schlagenhaufer R, Sprenger R, Roots I, Brinkmann U. Pharmacogenetics
Laboratory, Epidauros Biotechnology AG, Bernried, Germany. BACKGROUND:
Exposure to sunlight may cause sunburn, skin cancer or phototoxic
reactions to certain drugs such as Hypericum extract. All these are
ultraviolet B (UVB)-mediated reactions which may be modulated by
individual genetic susceptibility. UVB exposure results in oxidative
stress. Many products of oxidative stress are detoxified by
glutathione-S-transferases mu 1 (GSTM1) and theta 1 (GSTT1). Deletion
polymorphisms (genotype *0/*0) of GSTM1 and GSTT1 occur in 50% and 20%
of Caucasians, respectively. By affecting the individual ability to
detoxify oxidative stress-related products, they may influence the
severity of the cutaneous photoreaction. METHODS: Minimal erythema
doses (MED) of UVB irradiation on the skin were determined in 110
subjects who were selected according to their GSTT1 genotype (28
GSTT1*0/*0, 54 GSTT1*A/*0, and 28 GSTT1*A/*A). Genotypes were detected
with novel polymerase chain reaction (PCR) assays that allow the
differentiation between homozygous and heterozygous GSTT1 and GSTM1
deletions. RESULTS: In the absence of GSTT1 enzyme, the susceptibility
of individuals to UVB-induced inflammatory skin reactions increased
significantly (p = 0.02, ANCOVA). 'Gene-equivalents' were calculated
from the number of functional GSTM1 and GSTT1 alleles as a measure of
the gene-dose. UVB sensitivity correlated with gene dose up to a
threshold above which additional GSTT1 or GSTM1 alleles did not
provide additional protection. Volunteers who were homozygously
deficient in GSTT1 and GSTM1 were most sensitive to UVB.
Interestingly, individuals with high GSTM1 gene-doses showed increased
photosensitization after administration of Hypericum extract (St.
John's wort). CONCLUSION: Individuals harboring the *0/*0 genotype of
GSTT1 and/or GSTM1 showed enhanced UVB-induced cutaneous damage.
Moreover, GST genotypes modulated Hypericum-induced
photosensitization. PMID:
12083949…………………………………
(18) Zhonghua Yu Fang Yi Xue Za Zhi 1992 May;26(3):162-4 [The
aflatoxins and liver cancer in Guangxi, China] [Article in Chinese] Yu
SZ. Shanghai Medical University. The AFB1 intake and the AFM1
excretion of 81 households in 10 villages, Guanxi were investigated
using the ELISA method. The results showed that there was positive
correlation between PLC mortality and AFB1 intake from corn and peanut
oil, but not from rice. The results of stepwise regression showed that
main factors were AFB1 intake of males, AFM1 excretion of females and
consumption of corn. The results showed that aflatoxins were
correlated with mortality rates of liver cancer. Further investigation
needs to be carried out in case-control and cohort studies. PMID:
1395958…………………………..
Steve Harris
<9259eb2.02070...@posting.google.com>...
>"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
news:<agfkum$48r$1...@slb4.atl.mindspring.net>...
>> GeoWCherry wrote in message
<20020709115951...@mb-fp.aol.com>...
>>
>> >C'mon, Steve, don't tell us what doesn't
>> >work, tell us three things that DO work!
>> >You're a smart scientist and many of us
>> >(I sure am) are bioinformatic laymen. Tell
>> >me three more things that do work. I'll
>> >start with one: statin drugs (not taken at
>> >the same time as antioxidants). Now tell
>> >us three more things that work. My life
>> >hangs in the balance. Post up!
>>
>> COMMENT:
>>
>> You got the "drug" for which there's best evidence for life extension
(not
>> the same as anti-aging). The evidence for statins as a life extension
pill
>> is best of all....
>> And hell yes, I take a statin (pravachol>..
> SBH
>
>who are pregnant or nursing or may become pregnant, or people with
>liver problems. And because serious side effects can result, patients
>should tell their doctor about any unexplained muscle pain or weakness
COMMENT:
It doesn't. Most of what you've written is is from drug company lawyers
bibbling scribs for package inserts/PDR which will relieve them of maximal
responsiblity. It has almost nothing to do with clinical reality.
Statins are generally well-tolerated. Heart attacks and coronary disease
generally aren't.
Therefore (apologies to Larry Hart):
I'll drink menhaden
Oil, and take a statin
Pill or two.
And add an aspirin to
The brew
You can't be half-assed
Avoiding bypass
Surgery.
It clots your brain, you see
Suddenly...
-- Doc Harris
Peter H Proctor
>
> It doesn't. Most of what you've written is is from drug company lawyers
> bibbling scribs for package inserts/PDR which will relieve them of maximal
> responsiblity. It has almost nothing to do with clinical reality.
>
> Statins are generally well-tolerated. Heart attacks and coronary disease
> generally aren't.
Personally, Tho my cholesterol levels are not particularly high, I
take Lipitor, which has additional good effects on blood lipids in addition
to lowering cholesterol.
Arguably, the side effect of most concern with these drugs is rare
muscle breakdown with kidney failure caused by the products of this cloging
the kidneys. Personally, I'll take my chances.
A few years ago, I read an interesting analysis in the Lancet (?)
which showed administering statins to persons at risk was the most
cost-effective singe intervention in preventive medicine, next to low-dose
aspirin.
This weeks "The Lancet" reviews all the usual techniques ( statins,
controlling hypertension, aspirin, diet etc. ) for preventing heart
attacks and concludes they are mostly additive. In theory at least, In
is possible to cut the incidence of heart attacks by three-quarters using
them in combination. For some reason, they don't mention homocysteine,
which may be as important as cholesterol. A few weeks ago, an article in
the same journal reported that once you have sufficient folate, B12 seems
to be the controlling thing in homocysteine levels.
Dr P
Thomas Carter
snip
> A few years ago, I read an interesting analysis in the Lancet (?)
> which showed administering statins to persons at risk was the most
> cost-effective singe intervention in preventive medicine, next to low-dose
> aspirin.
Hi Dr,
The Lancet was wrong. Fish oil capsules beat both drugs hands down,
and with fewer side effects, altho there are nagging doubts about the
possibility that it is pro-aging due to the hi number of double bonds
in the carbon chain which may promote oxidative stress.
> This weeks "The Lancet" reviews all the usual techniques ( statins,
> controlling hypertension, aspirin, diet etc. ) for preventing heart
> attacks and concludes they are mostly additive. In theory at least, In
> is possible to cut the incidence of heart attacks by three-quarters using
> them in combination. For some reason, they don't mention homocysteine,
> which may be as important as cholesterol. A few weeks ago, an article in
> the same journal reported that once you have sufficient folate, B12 seems
> to be the controlling thing in homocysteine levels.
>
> Dr P
This is interesting supporting data for the Nurses' health study which
indicates that a whopping 82% reduction in cardiac events can be had
by a few easily accomplised life style changes. Three percent of the
nurses were in the low risk group. This is not theory, but an actual
accomplishment by almost 3,000 nurses.
I have another study which shows much the same and that it translates
into a nine year survival advantage.
Thomas
Results. Many of the factors were correlated, but each independently
and significantly predicted risk, even after further adjustment for
age, family history, presence or absence of diagnosed hypertension or
diagnosed high cholesterol level, and menopausal status. Women in the
low-risk category (who made up 3 percent of the population) had a
relative risk of coronary events of 0.17 (95 percent confidence
interval, 0.07 to 0.41) as compared with all the other women.
Eighty-two percent of coronary events in the study cohort (95 percent
confidence interval, 58 to 93 percent) could be attributed to lack of
adherence to this low-risk pattern (77% reduction with just folate,
B6, and alcohol. But this also serves as corroboration of the 77%
figure. Also actual adherence to the lifestyle was probably not 82%!)
A national study found people could add from 5 to 9.5 years to their
lives by maintaining a low risk cardiac profile. Researchers measured
long-term mortality rates of more then 366,000 participants and found
that nonsmokers with cholesterol levels less than 200 mg/dL and blood
pressure readings under 120/80 had significantly less heart disease
and fewer deaths than their counterparts. The study excluded people
with a history of diabetes or heart attack. Although previous reports
have supported the risk factor theory with estimated statistics, these
studies were too small for accurate measurement.
Clinicians calculated the new information using results from two
long-term studies, one conducted over a 22-year period. Only five to
ten percent of the subjects qualified as low risk. Among all age
groups, deaths attributed to heart disease comprised only six to eight
percent of all deaths among those at low risk, compared to 25 to 29
percent in the other subjects.
In the low risk population, deaths from heart disease were 77 to 92
percent less, deaths from stroke 52 to 76 percent less, and deaths
from all causes 50 to 58 percent less for men and 40 percent less for
women. And men in the low risk group lived 91/2 years longer.
Elzinator
>"Peter H Proctor" <d...@drproctor.com> wrote in message news:<FED37A2B2455A44A.33840DDD...@lp.airnews.net>...
>snip
>
>> A few years ago, I read an interesting analysis in the Lancet (?)
>> which showed administering statins to persons at risk was the most
>> cost-effective singe intervention in preventive medicine, next to low-dose
>> aspirin.
>
>Hi Dr,
>The Lancet was wrong. Fish oil capsules beat both drugs hands down,
>and with fewer side effects, altho there are nagging doubts about the
>possibility that it is pro-aging due to the hi number of double bonds
>in the carbon chain which may promote oxidative stress.
Several studies provide evidence that co-ingestion of vitamin E with
omega-3/fish oil attenuates oxidation. I don't recall the markers
analyzed as I read the studies over a year ago.
Much anecdotal testimony (clinical lipid profiles) supports the
evidence in studies that fish oil does indeed reduce total
triacylglycerols and LDL.
Elzi
<insert whatever here>
Paul Rogers
<elzi...@planetclaire.not> wrote:
>Much anecdotal testimony (clinical lipid profiles) supports the
>evidence in studies that fish oil does indeed reduce total
>triacylglycerols and LDL.
TG big time, but not LDL. Probably raises it slightly.
Paul R
Elzinator
The changes in both LDL and HDL in the studies are disparate, but the
trend is that LDL is reduced. The data on HDL has been almost
equivocally no change, increase or decrease. Usually the changes in
ratio of HDL:LDL has been favorable.
Elzi
<insert whatever here>
Tom Matthews (Paul Wakfer)
Just one more of dozens of studies which show that Aubrey de Grey's "one year at
most life extension from current methods" is completely wrong. It is just such
studies and other evidence which abound in the literature, and of which he
cannot be ignorant, which makes one question his objectivity and perhaps even
his motives, IMO.
--Tom Matthews (Paul Wakfer)
MoreLife for the rational - http://morelife.org
Reality based tools for More Life in quantity & quality
Ben
http://www.alexchiu.com/affiliates/clickthru.cgi?id=lovechrist
Paul Rogers
news:ef5cju05iae4bskhc...@4ax.com...
Could you post study(s) that show LDL is reduced after fish oil
supplementation? I have not been able to detect any trend downward in
studies but there does seem to be a trend upward.
Overall, cardiovascular benefits may be enhanced, but let's sort this out
for the sake of accuracy.
Paul R
Aubrey de Grey
Thomas Carter wrote:
> This is interesting supporting data for the Nurses' health study which
> indicates that a whopping 82% reduction in cardiac events can be had
> by a few easily accomplised life style changes. Three percent of the
> nurses were in the low risk group. This is not theory, but an actual
> accomplishment by almost 3,000 nurses.
Stampfer et al, N Engl J Med 2000 Jul 6;343(1):16-22.
> I have another study which shows much the same and that it translates
> into a nine year survival advantage.
Stamler et al, JAMA 1999 Dec 1;282(21):2012-2028.
There are two weak link in your summary above. The first is your use
of "easily accomplised". From Stampfer et al:
> We defined subjects at low risk as those who were not currently
> smoking, had a body-mass index (the weight in kilograms divided by the
> square of the height in meters) under 25, consumed an average of at
> least half a drink of an alcoholic beverage per day, engaged in
> moderate-to-vigorous physical activity (which could include brisk
> walking) for at least half an hour per day, on average, and scored in
> the highest 40 percent of the cohort for consumption of a diet high in
> cereal fiber, marine n-3 fatty acids, and folate, with a high ratio of
> polyunsaturated to saturated fat, and low in trans fat and glycemic
> load, which reflects the extent to which diet raises blood glucose
> levels.
Like it or not, giving up smoking is NOT easily accomplised by most
people. Lowering one's BMI considerably is arguably even harder. We
all know well that the things listed above are risk factors for heart
disease; I'd be the last to deny it. In the Stamler study, high risk
was defined using serum cholesterol levels, history of diabetes or
heart attack, and ECG abnormalities -- again, factors not accurately
describable as "easily" modified to the extent necessary to move one
out of the high risk bracket.
The second weak link is the relationship to life expectancy. The
Stampfer study looked for 14 years at people who were between 30 and
55 at the start. Thus, no one in the study had even reached the life
expectancy for US females by the end of the study, so it was looking
at early death, not at life expectancy. The Stamler study is the
same -- even in the high risk category under 1/4 of the subjects died
in the study period.
Tom Matthews wrote:
> Just one more of dozens of studies which show that Aubrey de Grey's
> "one year at most life extension from current methods" is completely
> wrong. It is just such studies and other evidence which abound in the
> literature, and of which he cannot be ignorant, which makes one
> question his objectivity and perhaps even his motives, IMO.
Tom, I would welcome your explicit conjecture as to what my motives
are. I don't accuse you of having questionable motives just because
you leap to firm and insulting conclusions before hearing both sides
of a discussion (to wit, my reply to Thomas above). I do, however,
question your objectivity.
Aubrey de Grey
Thomas Carter
Fish oil has been clearly shown by many studies to raise LDL and lower
the HDL/LDL ratio, and there is little data to the contrary, sorry.
Thomas
> <insert whatever here>
Tom Matthews (Paul Wakfer)
I have no idea what your motives might be, but I certainly question your
objectivity when you resort to an argument that something is "hard to do"
as a defense of your position that using currently available methods will
not extend anyone's life more than one year from simply an "ad lib" diet
and lifestyle.
Furthermore, (as I have stated before) motives have little bearing on my
approval or condemnation of someone's actions. Only the harm done by the
effects of those actions is important.
Peter H Proctor
<t...@morelife.org> wrote:
Re Statins, diet, etc.
>Just one more of dozens of studies which show that Aubrey de Grey's "one year at
>most life extension from current methods" is completely wrong.
Actually, I think Aubrey is talking about interference with
the aging process itself, not the age-related degenerative diseases
that most people die of. The latter is almost trivial.
Having read his books, papers, etc. I can testify that
Aubrey is obviously a very smart, capable person and no doubt knows
the difference<G>. Perhaps, as is customary when talking to a
knowledgeable audience, he likes to use short-hand, assuming that
his readers will understand what his subject is.
> It is just such
>studies and other evidence which abound in the literature, and of which he
>cannot be ignorant, which makes one question his objectivity and perhaps even
>his motives, IMO.
Bullsh!t..... He just is not talking about what you think
he is.... BTW, it is really tacky to impunge someones' motives,
agree with his conclusions or not.
Dr P
Aubrey de Grey
Peter Proctor wrote:
> > Just one more of dozens of studies which show that Aubrey de Grey's "one
> > year at most life extension from current methods" is completely wrong.
>
> Actually, I think Aubrey is talking about interference with
> the aging process itself, not the age-related degenerative diseases
> that most people die of. The latter is almost trivial.
>
> Having read his books, papers, etc. I can testify that
> Aubrey is obviously a very smart, capable person and no doubt knows
> the difference<G>. Perhaps, as is customary when talking to a
> knowledgeable audience, he likes to use short-hand, assuming that
> his readers will understand what his subject is.
At the risk of shortening readers' lives by giving them a heart attack,
I must clarify that Tom was right and Peter is wrong about what I have
been talking about in this thread. While it may be useful (though not
very easy) for those interested in understanding aging to distinguish
between aging and age-related degenerative diseases, it is a good deal
less useful for those interested in life extension. If something kills
lots of us, us, I think it's pretty important to deal with it, so the
simple question of life extension is indeed what I was discussing. I
think that gerontologists, and even most life-extensionists, tend to
(or at least appear to) agree with Peter that age-related degenerative
diseases are "almost trivial", and that this is a bad mistake, since
(to take the best example) cancer is in my view the single trickiest
aspect of aging to postpone by more than a decade or so. Whether we
call something a disease seems to be determined by how many people it
kills (or severely debilitates) at ages below the life expectancy, and
this has not much to do with how many people it kills in total or how
hard it is to fix.
I should also emphasise that my generalisation about only getting on
the order of a year by current methods is just that: a generalisation.
If forced to estimate what proportion of people could gain 5-10 years
(by virtue of being at high risk for something or other that is fixed
to a large extent by current methods), I would say 10-20%. Since we
can't know confidently whether we're in that 10-20% or not, I broadly
agree with Bruce Ames that it makes sense to take a multivitamin a day
even if one thinks one's diet is good, and I seem to have said so here
in the past (on March 14th of this year and Jan 4th of 2001).
Aubrey de Grey
Peter H Proctor
wrote:
snip...
> I
>think that gerontologists, and even most life-extensionists, tend to
>(or at least appear to) agree with Peter that age-related degenerative
>diseases are "almost trivial", and that this is a bad mistake, since
>(to take the best example) cancer is in my view the single trickiest
>aspect of aging to postpone by more than a decade or so.
For one thing, the majority of cancers get "cured".
> Whether we
>call something a disease seems to be determined by how many people it
>kills (or severely debilitates) at ages below the life expectancy,
It is not quite that diffuse. Physicians call something a
disease partially because it has a specific set of symptoms, an
etiology, etc.. but primarily because it produces a specific set of
morphological changes that you can see under a microscope. Least
that is what I do, having trained as a Pathologist<G>...
> and
>this has not much to do with how many people it kills in total or how
>hard it is to fix.
The problem is that these diseases have specific etiologies
that are only secondarily related to age. E.g., the older you
are, the more likely it is that the pathogenesis has had time to work
itself out.
E.g., the pathogenesis of atherosclerosis is becomng pretty
well understood. The 80% or so of people who don't die of cancer
almost all die of one of its consequences--- mainly, heart attack or
stroke. Aterhosclerosis is now thought to play a key role in senile
dementia. So anything that prevents atherosclerosis or its
sequelae is "life extending".
>Snip.... Since we
>can't know confidently whether we're in that 10-20% or not, I broadly
>agree with Bruce Ames that it makes sense to take a multivitamin a day
>even if one thinks one's diet is good, and I seem to have said so here
>in the past (on March 14th of this year and Jan 4th of 2001).
A good start, if only because folate, B12, and B6 lower
homocysteine levels. But there is other stuff too, Here is
something from last Week's "The Lancet". ( Volume 360, Number 9326
06 July 2002 ).
"Two decades of progress in preventing vascular disease"
Snip........." The past 25 years have seen the establishment of
aspirin, ß-blockers, ACE-inhibitors, and lipid-lowering therapies to
lower the risk of future vascular events, by about a quarter each,
in high-risk patients (panel). The benefits of each intervention
appear to be largely independent, so that when used together in
appropriate patients it is reasonable to expect that about two-thirds
to three-quarters of future vascular events could be prevented. Add
to this the potential benefits of quitting in smokers ( which lowers
the risk of myocardial infarction by a half ), and blood-pressure
lowering ( a 10 mm Hg reduction in systolic blood pressure could
reduce the risk of vascular events by a quarter ) in hypertensive
patients, and it may be possible to lower the risk of future events by
more than four-fifths in high-risk individuals. Therefore, the
potential gains from the combination of currently known preventive
strategies are large."
Dr P
Thomas Carter
Hi Aubrey,
Quite right. But two thirds of Americans don't smoke and about 45%
have BMI's lower than 25, and these people have much lower risks of
diabetes, ECG abnormalties, etc. I don't think its too far off to call
being in this group easy. Granted its much harder for some than
others. That would be the group that must GET there.
> The second weak link is the relationship to life expectancy. The
> Stampfer study looked for 14 years at people who were between 30 and
> 55 at the start. Thus, no one in the study had even reached the life
> expectancy for US females by the end of the study, so it was looking
> at early death, not at life expectancy. The Stamler study is the
> same -- even in the high risk category under 1/4 of the subjects died
> in the study period.
>
But the Stamler study specified a life span increase of 9.5 years. The
Stampfer study included mortalities in their cardiac events. Early
deaths are of course quite diminishing to life expectancy.
Thomas
Peter H Proctor
> >can't know confidently whether we're in that 10-20% or not, I broadly
> >agree with Bruce Ames that it makes sense to take a multivitamin a day
> >even if one thinks one's diet is good, and I seem to have said so here
> >in the past (on March 14th of this year and Jan 4th of 2001).
>
> A good start, if only because folate, B12, and B6 lower
> homocysteine levels.
E.g.
Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on
progression of subclinical atherosclerosis: a randomised, placebo-controlled
trial
E G J Vermeulen, et al, Lancet 2000; 355: 517-22
Summary
Background A high plasma homocysteine concentration is associated with
increased risk of atherothrombotic disease. We investigated the effects of
homocysteine-lowering treatment (folic acid plus vitamin B6) on markers of
subclinical atherosclerosis among healthy siblings of patients with
premature atherothrombotic disease. snip.....
Interpretation: Homocysteine-lowering treatment with folic acid plus
vitamin B6 in healthy siblings of patients with premature atherothrombotic
disease is associated with a decreased occurrence of abnormal exercise
electrocardiography tests, which is consistent with a decreased risk of
atherosclerotic coronary events.
Aubrey de Grey
Peter Proctor wrote:
> For one thing, the majority of cancers get "cured".
Briefly...
> > Whether we
> >call something a disease seems to be determined by how many people it
> >kills (or severely debilitates) at ages below the life expectancy,
>
> It is not quite that diffuse. Physicians call something a
> disease partially because it has a specific set of symptoms, an
> etiology, etc.. but primarily because it produces a specific set
> of morphological changes that you can see under a microscope.
Sure, but those changes have to be identified and characterised in
order to be defined as the signature of the disease, and that needs
people to be interested in the changes, and that (I claim) generally
needs society to want to avoid them (and to believe they might be
able to) by medical means, and that in turn doesn't happen for most
things that are a few years too slow to be the most visible thing
that kills lots of us. I'm saying that the sociology drives the
medicine. If we actually did (miraculously) push atherosclerosis,
Alzheimer's and cancer back by 15 years, I bet that a lot of things
that people get now but don't die of because they die of something
else first would become interesting enough to be elevated to the
status of "disease".
> The problem is that these diseases have specific etiologies
> that are only secondarily related to age. E.g., the older you
> are, the more likely it is that the pathogenesis has had time to
> work itself out.
>
> E.g., the pathogenesis of atherosclerosis is becomng pretty
> well understood. The 80% or so of people who don't die of cancer
> almost all die of one of its consequences--- mainly, heart attack or
> stroke. Aterhosclerosis is now thought to play a key role in senile
> dementia. So anything that prevents atherosclerosis or its
> sequelae is "life extending".
Yes, totally agreed. This is why I'm currently focusing my efforts
in the area of lysosomal enhancement with microbial enzymes on the
arterial macrophage, whose lysosomes fill up with oxysterols etc.
If macrophages could degrade everything they eat, it is completely
certain that atherosclerosis would not occur and very likely that
advanced atherosclerotic lesions could be induced to regress fast.
But this is really the flip-side of what I was saying. Just as it is
dubious to call (say) mitochondrial mutations part of "aging itself"
and therefore not a disease, it is dubious to call fatty streaks the
early stages of a disease and thus not part of "aging itself". For
practical purposes, the only question that matters is how smart we
need to become to fix the changes in question.
> Snip........." The past 25 years have seen the establishment of
> aspirin, ß-blockers, ACE-inhibitors, and lipid-lowering therapies to
> lower the risk of future vascular events, by about a quarter each,
> in high-risk patients (panel).
> ^^^^^^^^^^^^^^^^^^
>
> Background A high plasma homocysteine concentration is associated with
> increased risk of atherothrombotic disease. We investigated the effects
> of homocysteine-lowering treatment (folic acid plus vitamin B6) on
> markers of subclinical atherosclerosis among
> healthy siblings of patients with premature atherothrombotic disease
> ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
Forgive me a moment of deja vu :-)
Aubrey de Grey
Aubrey de Grey
Thomas Carter wrote:
> the Stamler study specified a life span increase of 9.5 years.
Not quite: actually an "Estimated greater life expectancy", which in
fact (if you look at the statistical methods) means an extrapolated
greater life expectancy based on the early deaths. By that sort of
method, CR would be stated to shorten lifespan, since in most studies
there are more early deaths in the CR than the AL group.
> Early deaths are of course quite diminishing to life expectancy.
No they're not, they're only mildly diminishing to life expectancy,
because they're (by definition) the deaths of a minority of the total
population.
Aubrey de Grey
Elzinator
Tom,
Frankly, I haven't been able to keep up with the studies for the last
8 months except for the relationship of n-3 fatty acids, immune system
and insulin activity. The last I recall when reading the studies
related to lipid profiles (~year ago?), the trend in LDL changes was
generally a reduction (induced by downregulation of a hepatic gene?).
However, the determining variables appeared to be dose, caloric intake
and total dietary fat intake.
If there has been a meta-analysis since then demonstrating the
converse, I stand corrected.
Elzi
<insert whatever here>
Peter H Proctor
"Aubrey de Grey" <ag...@mole.bio.cam.ac.uk> wrote in message
news:ah9vi8$676$1...@pegasus.csx.cam.ac.uk...
>
> Peter Proctor wrote:
> > It is not quite that diffuse. Physicians call something a
> > disease partially because it has a specific set of symptoms, an
> > etiology, etc.. but primarily because it produces a specific set
> > of morphological changes that you can see under a microscope.
>
> Sure, but those changes have to be identified and characterised in
> order to be defined as the signature of the disease, and that needs
> people to be interested in the changes,
The symptomology and the disease-related macro and microscopic changes in
the "meat" were mostly characterized by 100 years ago. Some have been
recognized for millenia.
> If we actually did (miraculously) push atherosclerosis,
> Alzheimer's and cancer back by 15 years, I bet that a lot of things
> that people get now but don't die of because they die of something
> else first would become interesting enough to be elevated to the
> status of "disease".
As a practical matter, there are no unknown "diseases" or causes of
death waiting to be discovered. Even the very oldest people die from one
of the regulars. BTW, thoug I have since wandered away from the area,
during my pathology residency, my sometime job used to be figuring out what
killed someone by cutting them open and taking a look.. Real ( er)
hands-on experience. The big thing is cardiac arrythmia secondary to
whatever....
snip... Stuff I agree with...
>
> But this is really the flip-side of what I was saying. Just as it is
> dubious to call (say) mitochondrial mutations part of "aging itself"
> and therefore not a disease, it is dubious to call fatty streaks the
> early stages of a disease and thus not part of "aging itself".
Depends on who you talk to<G>.
Dr P
Gene Goldenfeld
> >he is.... BTW, it is really tacky to impunge someones' motives,
> >agree with his conclusions or not.
I don't have anything to say about the anti-aging discussion, but
the idea that ..."it is really tacky to impunge someones'
motives..." is a call for dishonesty, depending on the forum.
What's not usually done in scientific forums, such as in journal
articles and conferences, may be appropriate in public forums. If
someone's motives for career, fame, politics and money form an
essential element of what's driving the substance of his
arguments, then it could be dishonest *not* to characterize them
as such (a tactical question). Here's an example from an article
in the NY Times Magazine of Sept 1 ("Totally Uncooked") that I
find wholly appropriate. It concerns the apparent growth in the
raw-food subculture in the US and focuses in particular on
Michael and Roxanne Klein, the latter the owner of a raw food
restaurant in California:
"It would be easy to dismiss raw cookery as kookery, and many do.
But the rise of raw also reflects something about America's
current mood. Extreme dietary regimens tend to crop up during
times of crisis as a simple fix for society's ills."
Gene Goldenfeld
Tom Matthews (Paul Wakfer)
> On Thu, 18 Jul 2002 18:21:53 GMT, d...@drproctor.com (Peter H Proctor)
> wrote:
>
>
>>On Wed, 17 Jul 2002 23:42:14 -0400, "Tom Matthews (Paul Wakfer)"
>><t...@morelife.org> wrote:
>>Re Statins, diet, etc.
>>
>>
>>>Just one more of dozens of studies which show that Aubrey de Grey's "one year at
>>>most life extension from current methods" is completely wrong.
>>>
>> Actually, I think Aubrey is talking about interference with
>>the aging process itself, not the age-related degenerative diseases
>>that most people die of. The latter is almost trivial.
>>
>
> I'd say so, too. At least this is whats coming across to me, not even
> being a native english speaker.
If you read the original again in full, it is very clear the Aubrey does *not*
apply his "one year at most life extension from current methods" to reduction of
only age-related degenerative diseases, but instead to *all* causes of
mortality. Aubrey apparently believes that while current methods may reduce
morbidity and acute mortality, they will affect the end-result age of death
very, very little.
It is in this particular respect that we greatly differ.
I maintain that the result will be closer to 10-15 years (average).
Michael Price goes much further in maintaining that it will be 20-30 year.
>> Having read his books, papers, etc. I can testify that
>>Aubrey is obviously a very smart, capable person and no doubt knows
>>the difference<G>.
I have never questioned his intelligence, scientific knowledge and acumen. I do
question some of his value judgments and his overall wisdom. Many people are
highly intelligent in one area of thought, but neither wise nor consistent
overall. In fact, in my experience this is true for most intelligent and highly
accomplished people. It makes good sense, logically, that this would be so,
because if one spends the necessary time to be highly accomplished in any one
area one does not have the time to think deeply and clearly about most other
areas. I have spent my lifetime attempting to study and think clearly and
consistently in very broad areas of knowledge and thought. Perhaps that is why I
have not had the time to become significantly accomplished and productive in any
one area.
>>Perhaps, as is customary when talking to a
>>knowledgeable audience, he likes to use short-hand, assuming that
>>his readers will understand what his subject is.
>>
>>
>>>It is just such
>>>studies and other evidence which abound in the literature, and of which he
>>>cannot be ignorant, which makes one question his objectivity and perhaps even
>>>his motives, IMO.
>>>
>> Bullsh!t..... He just is not talking about what you think
>>he is.... BTW, it is really tacky to impunge someones' motives,
>>agree with his conclusions or not.
>>
>
> I'd like to second this. And I believe Tom is really getting carried
> away here. Probably because he thinks that Aubrey, being intelligent
> and "in the know" denies "the truth" despite better knowledge.
People often subconsciously "evade" things which do not fit with (or are
contrary to) what they want to see happen in the world. Aubrey very much wants
to see more money spent on research to affect fundamental aging processes and I
too want this just as much as he does. However, being older than he (and seeing
many other good people who are older than he), I am not going to deny what I see
as good evidence that current methods can greatly help people to stay alive
until these fundamental anti-aging breakthroughs are available. Nor am I alone
in this viewpoint. Many on this list agree with me (witness Peter's statement,
"The latter is almost trivial").
In addition, Aubrey and I greatly disagree about how the financing of
the development of fundamental antiaging processes should be done. My view is
that it should not be financed by either of the following:
1) Stealing money through government forced taxation.
2) Having people forgo current methods (particularly supplements) and using the
money saved.
My arguments against 1) are that
a) Theft is *never* a moral course of action (read - of long run benefit to all).
b) Philosophically, no "good" can come from immoral methods.
c) To the extent that certain members of the public desire the development of
fundamental antiaging methods they will finance them voluntarily. To the extent
that certain others do not, they should not be forced to finance them.
My arguments about 2) are:
a) This is a conflict between those who are currently less than 40 ("young") and
more than 60 ("old") (in rough terms). In essence, Aubrey is asking the "old" to
forgo the possibility of extended life so that it may come more certainly to the
"young". Aubrey appears not to be doing this intentionally or consciously.
However, his myopia wrt the implications of published studies re the multiple
health and disease (mortality and morbidity) inhibiting effects of current life
extension methods has that effect, whatever its other purposes may be.
b) Moreover, this "forgoing of extended life for those currently 'old'" is also
negative wrt to its effects on hastening the development of fundamental
antiaging methods, since the more people that have some hope to benefit from
them, the more chance these benefits have to come sooner rather than later.
Peter H Proctor
<t...@morelife.org> wrote:
>If you read the original again in full, it is very clear the Aubrey does *not*
>apply his "one year at most life extension from current methods" to reduction of
> only age-related degenerative diseases, but instead to *all* causes of
>mortality. Aubrey apparently believes that while current methods may reduce
>morbidity and acute mortality, they will affect the end-result age of death
>very, very little.
He has a point--- from personal experience that any doc
will reinforce--- at present, nobody lives long enough to die of
old-age. Everybody dies prematurely of some defined age-related
degenerative disease ( mostly atherosclerosis or cancer ), if
infection or accident doesn't kill them first. So we really have
not a clue what would happen if swe could get rid of _that_ aspect of
mortality.
Dr P
Tom Matthews (Paul Wakfer)
Given that (among other leading edge chemicals) oral use of PBN *is* one of
those "currently available life extending methods" (though with some difficulty
of procurement), your statement above does not seem to be consistent with
statements in your previous posts.
In any case, no one will *ever* die merely of "old age"! All deaths have a
particular cause which can potentially be inhibited and delayed with the correct
method(s), some of which may even be available now.
In this sense, everyone will always die "prematurely", because something could
always have been done to delay or prevent the acute cause of that death.
As I have stated elsewhere, the goal of my life extension efforts is to attempt
to inhibit, delay or prevent ALL POSSIBLE causes of death at one and the same
time to the extent to which this is consistently possible.
michaelprice
> Just one more of dozens of studies which show that Aubrey de Grey's
> "one year at most life extension from current methods" is completely
> wrong.
Agreed. I'd be more worried if he claimed an extra decade would be
typical - it would be more credible, but *one year*; hah!
[.........]
> If you read the original again in full, it is very clear the Aubrey
> does *not* apply his "one year at most life extension from current
> methods" to reduction of only age-related degenerative diseases, but
> instead to *all* causes of mortality. Aubrey apparently believes that
> while current methods may reduce morbidity and acute mortality, they
> will affect the end-result age of death very, very little.
>
> It is in this particular respect that we greatly differ.
> I maintain that the result will be closer to 10-15 years (average).
> Michael Price goes much further in maintaining that it will be 20-30 year.
Actually I maintain a lot more than that. I think Aubrey is off by *two*
orders of magnitude, which will no doubt confirm his belief that I'm
completely off my trolley.
In order of decreasing probability, we can expect dietary supplements to
yield a mean average lifespan increase of at least either:
· 27%. Extrapolating purely from the mammalian lifespan data. Assumes no
synergy between the known anti-aging micronutrients dietary RNA[2],
chromium[5] and vitamins B5 (pantothenate) [3] and B6 (pyridoxine) [6],
which is unrealistically pessimistic.
· 85%. Extrapolating from both the insect and mammalian lifespan data.
Allows for synergy (seen in insects[1b]) between the known mammalian
anti-aging micronutrients and vitamin B3 (niacinamide).
· 85% to 230%. Extrapolating from additional probable anti-aging
micronutrients magnesium, zinc, carnitine, alpha lipoic acid and vitamins B7
(biotin), B9 (folate) and B12 (cobalamin)). If all the probable anti-aging
cofactors work then an additional mean life extension of 85% *17/10 = 145%
is expected. In practice we must expect that some of the unproven but
probable micronutrients will be duds, so a more realistic total mean
lifespan extension would be somewhere in the range 85% to 230%; a doubling
or tripling of our mean average natural lifespan, 70 years, to between 140
and 250 years would be a reasonable expectation.
We can expect an associated maximum lifespan increase of approximately 63%
[7] of the mean average lifespan increase, i.e. in the range 54% to 145%, to
total 188 to 300 years.
Use of the health boosting micronutrients, selenium, the carotenoids and
various herbs[96] may help square the survival curve, raising the mean life
span closer the new maximum lifespan. Living to, and beyond, 200 years is
achievable right now.
Full references and reasoning available upon request in a 200+K word file.
[1b] The Use of Drosophila Melanogaster as a Screening Agent for Longevity
Factors. II. The Effects of Biotin, Pyridoxine, Sodium Yeast Nucleate, and
Pantothenic Acid on the Life Span of the Fruit Fly. Thomas S Gardner,
Journal of Gerontology 1(3) (1948): 9-13
[2a] The Effect of Yeast Nucleic Acid on the Survival Time of 600-Day-Old
Albino Mice. Thomas S Gardner, Journal of Gerontology 3(?) (1946): 445-452.
This reproduces the work of Robertson on lifelong administration of nucleic
acid enriched diets, at a lower dosage.
[2b] Influence of Nucleic Acids of Various Origin upon the Growth and
Longevity of the white mouse. TB Robertson in the Australian J of
Experimental Biology and Medical Science, 5, (1928): 46-67
16% mean life span extension. Maximum lifespan (last 10%) extended by
approximately 8 - 16%.
[3] Effect of pantothenic acid on the longevity of mice. Richard B Pelton
and Roger J Williams in Proceedings of the Society Experimental Biology &
Medicine 99 632-633, 1958. Mean lifespan extension of 19.5%. No maximum
lifespan data reported.
[4] How to re-energise old mitochondria without shooting yourself in the
foot. Driver C, Georgiou A in Biogerontology 2002;3(1-2):103-6
Nicotinamide increased mean lifespan in drosophila by 15%. Private
communication: Maximum lifespan (last 10%) also increased.
[5a] Composition and Biological Activity of Chromium-Pyridine Carboxylate
Complexes. GW Evans and DJ Pouchnik, Journal of Inorganic Biochemistry 49,
pg 177-187 (1993). Describes the action of dietary chromium picolinate
(relative to chromium chloride and chromium nicotinate) in reducing
glycation & plasma glucose levels in rats as they aged. (Submitted March
1992 for publication.)
[5b] Life span is increased in rats supplemented with a chromium-pyridine 2
carboxylate complex. Evans GW, Meyer LK in Adv Sci Res. 1994; 1:19-23.
[5c] Chromium picolinate increases longevity. Evans GW, Meyer LK in AGE
(the Journal of the American Aging Association) Oct 1992; 15(4), 134. 80%
of the rats receiving chromium picolinate outlived all the other treatment
groups, i.e. mean and maximum lifespan extended.
[5d] Chromium Picolinate. GW Evans, (1996) ISBN 0895299119.
Gives additional information about the Evans-Meyer-Pouchnik chromium
picolinate experiment on rats: Mean lifespan extension of 27%
[5e] The Longevity Factor: Chromium Picolinate. RA Passwater, (1993), ISBN
0879836199. Gives additional information about the Evans-Meyer-Pouchnik
chromium picolinate experiment on rats: Cohort maximum lifespan (last
survivor) extended by 17%, from 41 months to 48 months, extending the
previous species maximum by 15%. 30 rats, 10 in each group.
[6] Favorable Effects of Pyridoxine HCl on the aging process. Lindseth K,
Dictor M & Miquel J in AGE 5(4), 143, 1982. Late middle-age intervention
gave mean total lifespan extension of 11%. No maximum lifespan data
reported.
[7] Tetrahydrocurcumin Prolongs Survival Curves of Male C57BL Mice. Kitani
K, Osawa T in AGE 25, 2002 Middle age intervention resulted in mean
lifespan extension of 11%, maximum lifespan (last 10%) extended by 7%.
Curcumin, a saffron-yellow pigment, is one of the active ingredients of the
spice Turmeric (ginger family). The other curcuminoids in Turmeric may also
be potent antioxidants.
Cheers,
Michael C Price
Thomas Carter
Michael sent me his word file. (thx, Mike) While his two centuries
of life span hypothesis is outlandishly optimistic, he backs it up
with well over 100 references. This tightly reasoned article deals
mostly with B vitamins and their synergistic effects on health and
life span. But also touches on other supplements, and aging theory
with some very valid insights. It is more tightly reasoned and of
better quality than most published books or articles. I recommend it
as a must read, especially for anyone who does not supplement with a
B100 or at least a B50 complex vitamin. It has given me much more
respect for the B vitamins and more hope than the effects of these and
other natural interventions are additive in nature and consequently
can give us hope for a much greater life extension than I for one have
been expecting from my supplemental regimen. Could we hope for 200
years or more? Well, read his article and decide for yourself. I think
Michael's 200 years is at least as probable as Aubrey's one year.
Thomas
Tom Matthews (Paul Wakfer)
My comments below should be read with the knowledge that I have not read
Michael's word file, but am making them based on general principles.
Thomas Carter wrote:
> Michael sent me his word file. (thx, Mike) While his two centuries
> of life span hypothesis is outlandishly optimistic, he backs it up
> with well over 100 references. This tightly reasoned article deals
> mostly with B vitamins and their synergistic effects on health and
> life span.
But reasoning, however tight and logical, is not sufficient to make a case.
First, there is the matter of the evaluation of the *level of validity* which
should be attached to the evidence (and the level of validity of much of the
evidence that Michael has presented before has been very weak in the opinion of
most of us here including published scientists).
Second, there is the matter of the dearth of interventive (real cause and effect
determining) human experimentation using supplements (especially clearly
synergistic combinations) which to the shame of the biomedical establishment,
has not been and is not being adequately done. Without those results, no good
case can be made for Michael's extreme conjecture. (It is difficult enough to
make a good case even for my own more moderate conjecture of 10-15 years mean
and 20-30 years max life extension by current methods optimally applied.)
Third, "optimism" is not alone a valuable attribute. Only *reasonable* optimism
is conducive to maximizing one's long-range happiness, since only reasonable
optimism has sufficient chance of success that one will not be ultimately
disappointed and highly deflated.
> But also touches on other supplements, and aging theory
> with some very valid insights. It is more tightly reasoned and of
> better quality than most published books or articles.
To clarify here: I assume that you mean books and articles written for mass
consumption, rather than scholarly texts and treatises, and review articles
published in peer-reviewed journals.
> I recommend it
> as a must read, especially for anyone who does not supplement with a
> B100 or at least a B50 complex vitamin. It has given me much more
> respect for the B vitamins and more hope than the effects of these and
> other natural interventions are additive in nature and consequently
> can give us hope for a much greater life extension than I for one have
> been expecting from my supplemental regimen.
I don't think that I have ever seen you state what *are* your current
estimations (best hopes) for life extension from your own supplemental regimen
(which I expect it would be reasonable to say is the best that you think can be
done by current methods). Would you please tell us, so that we have some basis
for understanding your statement above?
> Could we hope for 200
> years or more? Well, read his article and decide for yourself. I think
> Michael's 200 years is at least as probable as Aubrey's one year.
That last sounds like a fair assessment, which I too would probably make after reading it.
Thomas Carter
Yes, too true. The tight and logical case is based for the most part
on scanty rodent evidence that is quite old and has not been verified.
I spoke more of hope than belief. For safe supplements this is another
way of saying the benefit/risk ratio is good enough for action.
>
> > But also touches on other supplements, and aging theory
> > with some very valid insights. It is more tightly reasoned and of
> > better quality than most published books or articles.
>
>
> To clarify here: I assume that you mean books and articles written for mass
> consumption, rather than scholarly texts and treatises, and review articles
> published in peer-reviewed journals.
Yes. But I would say it is as good as some stuff I've read in Medical
Hypothesis.
> > I recommend it
> > as a must read, especially for anyone who does not supplement with a
> > B100 or at least a B50 complex vitamin. It has given me much more
> > respect for the B vitamins and more hope than the effects of these and
> > other natural interventions are additive in nature and consequently
> > can give us hope for a much greater life extension than I for one have
> > been expecting from my supplemental regimen.
>
>
> I don't think that I have ever seen you state what *are* your current
> estimations (best hopes) for life extension from your own supplemental regimen
> (which I expect it would be reasonable to say is the best that you think can be
> done by current methods). Would you please tell us, so that we have some basis
> for understanding your statement above?
10 yrs (95% confidence level 5 to 20)
michaelprice
> >
> Hi,
> Michael sent me his word file. (thx, Mike) While his two
> centuries of life span hypothesis is outlandishly optimistic,
That is my gut feel as well, but when I look at the steps leading to this
conclusion they all seem so reasonable. Where did I go wrong? :-)
> he backs it up with well over 100 references.
Now over 230, and still growing.
> This tightly reasoned article deals
> mostly with B vitamins and their synergistic effects on health and
> life span. But also touches on other supplements, and aging theory
> with some very valid insights. It is more tightly reasoned and of
> better quality than most published books or articles. I recommend it
> as a must read, especially for anyone who does not supplement with a
> B100 or at least a B50 complex vitamin. It has given me much more
> respect for the B vitamins and more hope than the effects of these and
> other natural interventions are additive in nature and consequently
> can give us hope for a much greater life extension than I for one have
> been expecting from my supplemental regimen. Could we hope for 200
> years or more? Well, read his article and decide for yourself. I think
> Michael's 200 years is at least as probable as Aubrey's one year.
> Thomas
Thanks for the feedback. Still available upon request for anyone. Will
broadcast when closer to finalised.
Cheers,
Michael C Price
michaelprice
> I want to first thank Thomas for providing this review.
> My comments below should be read with the knowledge that I
> have not read Michael's word file, but am making them based on
> general principles.
>
> Thomas Carter wrote:
>
>> Michael sent me his word file. (thx, Mike) While his two centuries
>> of life span hypothesis is outlandishly optimistic, he backs it up
>> with well over 100 references. This tightly reasoned article deals
>> mostly with B vitamins and their synergistic effects on health and
>> life span.
>
> But reasoning, however tight and logical, is not sufficient to make
> a case. First, there is the matter of the evaluation of the *level of
> validity* which should be attached to the evidence
Naturally, the degree of validity or plausibility is crucial.
> (and the level of validity of much of the evidence that Michael has
> presented before has been very weak in the opinion of most of us
> here including published scientists).
I assume that this is reference to Aubrey de Grey and Steve Harris, both of
whom have (repeatedly) claimed that additional supra-RDA vitamin/mineral
intake is ineffective for normal healthy humans eating a well-balanced diet,
yet neither of them have felt the necessity to respond to my (repeated)
posting of evidence countering this claim.
> Second, there is the matter of the dearth of interventive (real cause and
> effect determining) human experimentation using supplements (especially
> clearly synergistic combinations) which to the shame of the biomedical
> establishment, has not been and is not being adequately done.
There is a wealth of experiments demonstrating the synergistic health
benefits in mammals (recently posted), which makes the extrapolation of
synergy to the lifespan results (so far only empirically demonstrated on
insects) plausible. Plus there is a strong theoretical reason, explained in
my monograph.
> Without those results, no good case can be made for Michael's extreme
> conjecture. (It is difficult enough to make a good case even for my own
> more moderate conjecture of 10-15 years mean and 20-30 years max
> life extension by current methods optimally applied.)
> Third, "optimism" is not alone a valuable attribute. Only *reasonable*
> optimism is conducive to maximizing one's long-range happiness, since
> only reasonable optimism has sufficient chance of success that one will
> not be ultimately disappointed and highly deflated.
Of course.
Cheers,
Michael C Price
Thomas Carter
> Thomas Carter:
> > >
> > Hi,
> > Michael sent me his word file. (thx, Mike) While his two
> > centuries of life span hypothesis is outlandishly optimistic,
>
> That is my gut feel as well, but when I look at the steps leading to this
> conclusion they all seem so reasonable. Where did I go wrong? :-)
>
I wouldn't say you went wrong, but I do think you went
outlandish. That is to say your hypothesis of over 200 years requires
an extremely high number of "ifs" to come in on the favorable side. So
while your extreme number is possible it is far from probable. As you
lower the target number reaching it becomes more probable. I have seen
many scientists err by assuming that their extrapolation of a curve
that has been verified in a certain range is valid for a much
different range. Archeologists and physicists come to mind. As to the
present question I'll give just one example of a probable reason that
would eliminate the two century life span due to the supplements you
spoke of. A 63% increase in the life of rodents gives no time for
death due to loss of dopamine producing cells in the substantia negri
portion of the brain. A similar extension of Life in humans would,
thus resulting in a high chance of Parkingson's disease. A big
unnoticed "if" in the hypothesis is that vitamins would eliminate this
natural aging force which we all are subject to at a very small rate
and which has been estimated to cause death by age 130 for anyone who
lives that long. One could list dozens or even hundreds of such "ifs".
Telomeres, lipofuscin, etc?
I take your hypothesis to implicitly mean a great extension of
life due only to the regimen you wrote about. When seen as only one
factor in the great amount of scientific progress we are experiencing,
the two century life span is a good deal more probable. To stay with
the PD example, if B vitamins can help get a person thru the next 30
years, there is a good chance that genetic engineering can eliminate
PD during that time. The same reasoning applies to telomere and
lipofuscin aging. So while I see the 200 yr life span due soley to the
supplementation of present day nutrients as outlandishly improbable, I
see it as only moderately improbable when all factors are considered.
I in fact see it worth reaching for.
Thomas
michaelprice
thanks for the feedback:
Assuming a 'normal' rate of nigral loss? I tend to regard PD as amenable to
anti-oxidant strategies to reduce the stress on the domaminergic substantia
nigra neurons, which is why I didn't cover it (or investigate it much,
admittedly). A PubMed trawl shows that my confidence is not entirely
misplaced. Antioxidants such as vitamin D, E, melatonin (methylated
serotonin) and flavonoids act as PD neuroprotectors. Mitochondrial decline
is implicated in PD which should respond to ALA and ALCAR. So I'm inclined
to think that the progression of PD would be slowed by as much as our lives
are extended by the micronutrients I'm megadosing with.
I believe most (all?) age-degenerative problems (e.g. lipofuscin build-up,
which, AFAIK, is not irreversible but a sign of decline in the efficiency of
our homeostatic mechanisms) are amenable to a similar sort of analysis.
Telomeres may be an exception, but their role in aging is currently unclear.
Cheers,
Michael C Price
Some refs re PD:
Neuroreport 2001 Dec 4;12(17):3871-5
Tissue distribution and neuroprotective effects of citrus flavonoid
tangeretin in a rat model of Parkinson's disease.
Datla KP, Christidou M, Widmer WW, Rooprai HK, Dexter DT.
PMID: 11726811
Free Radic Biol Med 2000 Mar 15;28(6):904-11
Melatonin suppresses iron-induced neurodegeneration in rat brain.
Lin AM, Ho LT.
PMID: 10802221
J Pineal Res 2001 Nov;31(4):356-62
Glutamate induces oxidative stress not mediated by glutamate receptors or
cystine transporters: protective effect of melatonin and other antioxidants.
Herrera F, Sainz RM, Mayo JC, Martin V, Antolin I, Rodriguez C.
PMID: 11703566
Free Radic Biol Med 2001 Apr 15;30(8):924-31
Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde
targets mitochondria.
Kristal BS, Conway AD, Brown AM, Jain JC, Ulluci PA, Li SW, Burke WJ.
PMID: 11295535
Brain Res 2001 Feb 16;892(1):211-7
Neuroprotective effect of vitamin E on the early model of Parkinson's
disease in rat: behavioral and histochemical evidence.
Roghani M, Behzadi G.
PMID: 11172767
Brain Res 2001 Jun 15;904(1):67-75
Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats.
Wang JY, Wu JN, Cherng TL, Hoffer BJ, Chen HH, Borlongan CV, Wang Y.
PMID: 11516412
michaelprice
> build-up, which, AFAIK, is not irreversible but a sign of decline
> in the efficiency of our homeostatic mechanisms) are amenable to
> a similar sort of analysis.
[116a] Effect of dietary vitamin E on lipofuscin accumulation with age in
the rat brain. Monji A, Morimoto N, Okuyama I, Yamashita N, Tashiro N in
Brain Res 1994 Jan 14;634(1):62-8
"dietary vitamin E clearly had a significant effect on lipofuscin
accumulation with age in the rat brain up until middle age, and that the
same effect became indistinct in the latter half of their life."
[116b] Effects of vitamin E on the blastogenic response of splenocytes and
lipofuscin contents in the hearts and brains of aged mice. Ma XY, Su YB,
Zhang FR, Li JF in
J Environ Pathol Toxicol Oncol 1996;15(1):51-3
"the lipofuscin level in the brains and hearts of aged mice declined
substantially with the VE supplementation (heart: p < 0.001, brain: p <
0.05). Furthermore, the effects of dietary VE on the serum VE and tissue
lipofuscin content in aged mice were much more obvious than in the young
animals."
[116c] Lipofuscin accumulation and its prevention by vitamin E in nervous
tissue: quantitative analysis using snail buccal ganglia as a simple model
system. Winstanley EK, Pentreath VW in Mech Ageing Dev 1985
Mar;29(3):299-307
"This diet prevented lipofuscin appearance in the young animals, and reduced
the lipofuscin content by 50% in the old animals. The findings provide
direct evidence that Vitamin E reduces lipofuscin accumulation in glial
cells in intact nervous tissue."
[] Long-term variations in cyclic light intensity and dietary vitamin A
intake modulate lipofuscin content of the retinal pigment epithelium.
Katz ML, Gao CL, Rice LM in J Neurosci Res 1999 Jul 1;57(1):106-16
"lipofuscin content is determined by a balance between the rates at which
lipofuscin is formed and at which it is eliminated"
Cheers,
Michael C Price
michaelprice
> Thanks for the feedback. Still available upon request for anyone. Will
> broadcast when closer to finalised.
My monograph on the subject of staying alive is now available on-line in
John de Rivaz's longevity report. I hope folks find it it helpful.
http://www.longevity-report.com/lr91.htm
My thanks to everybody who took the trouble to read the earlier version(s),
and for the feedback they gave me.
Cheers,
Michael C Price