48 replies to this topic

[Michael]

All:

This is my favorite passage from the study:

**********
We note that unlike CR, resveratrol did not reduce circulating IGF-1 levels (Figure 2B), and there was also no decrease in spontaneous tumors at the time of sacrifice (Supplemental Table S2). In particular, spontaneous liver tumors were abundant in mice fed the control diet or resveratrol, but rare in CR mice. Thus, although a low dose of resveratrol can improve quality of life by retarding aging parameters such as cardiac dysfunction, a nutritional or pharmaceutical strategy to also increase lifespan in mice will likely require blockage of the IGF-1 axis or its targets.
***********

And yet RSV does appear to fight cancer at higher dosage levels, does it not?

Yes -- under totally artificial conditions . RSV has been shown to inhibit (a) in vitro carcinogenesis, which can obviously be of zero evidential value on whether something really happens in the real world (although such studies are often helpful in elucidating the mechanisms whereby an effect already observed in vivo occurs); (b) cancer incidence or progression induced or promoted in vivo by nasty chemical carcinogens, in which case you're mostly looking at a stupid antioxidant, drug-detoxifying, or sometimes (eg in the colon) a cyclooxygenase-inhibiting effect, none of which has anything to do with prevention of "normal," age-related cancer (which primarily results from mutations induced by endogenous DNA damage during mitosis); or ( c ) in vivo in estrogen-sensitive cancer models (Transgenic Adenocarcinoma Mouse Prostate (TRAMP) mice, estrogen-sensitive transplanted human prostate or breast cancer lines, etc -- eg, (1,2)), which likely results from resveratrol's phytoestrogen properties -- which is risky business.

The alleged benefits even of soy phytoestrogens, which are much better-studied in humans (because we have done more clinical trials and, more importantly, have a lot of prospective epidemiology) remain highly ambiguous. As I have written elsewhere (slight edits in version below):

******
soy phytoestrogens are protective against prostate cancer in some animal models (including (3), which closely mirrors this [resveratrol] study [2] in design (TRAMP mice, initiated on genistein at age 5-6 weeks)), but while a reduction in prostate cancer incidence has been observed in soy consumers in some epidemiological studies, an American Heart Association Nutrition Committee Science Advisory for professionals concluded that

The efficacy and safety of soy isoflavones for preventing or treating cancer of the breast, endometrium, and prostate are not established; evidence from clinical trials is meager and cautionary with regard to a possible adverse effect.(4)

Indeed, a prospective epidemiological study in Japan found that

Intakes of genistein, daidzein, miso soup, and soy food were not associated with total prostate cancer. However, these four items decreased the risk of localized [ie, noninvasive, generally non-life-threatening -MR] prostate cancer. In contrast, positive associations were seen between isoflavones and advanced prostate cancer.(4)

This is especially important to note in the resveratrol prostate cancer study (2), since the animals began consuming a resveratrol-supplemented diet at age 5 weeks, as in the previous genistein report in the same model (3); this is at or only shortly after weaning (3-6 weeks), and before reproductive maturity (6-8 weeks). In this context, it is important to bear in mind the bimodal effects of soy phytoestrogens on breast cancer, depending on exposure times during the life cycle:

We and others have shown that both genistein and resveratrol can protect against mammary cancer in rodents. The timing of exposure to genistein appears critical for its mammary protective effects. It has been reported that genistein early in life causes enhanced mammary gland differentiation, alterations in cell proliferation and apoptosis, and upregulation of tumor-suppressor genes. With resveratrol in the diet, changes in cell proliferation and apoptosis in terminal ductal structures of the mammary gland might help to explain its protective effects.(6)

************


Note this last point, which is especially important in considering the time of exposure:

Similar observations have been made in humans: childhood exposure to genistein in soy or to some other bioactive food components reduces later breast cancer risk, although they may have no effect if consumed during adulthood. ... Many of these dietary exposures modify fetal and postnatal hormonal environment, including changing the concentrations of estrogens and leptin. The hormonal alterations then may induce persistent epigenetic changes ... The targets of epigenetic changes are likely to be the terminal end buds (TEBs), the structures where carcinogen-induced mammary tumors in rats and mice are initiated. ... Similar structures in women, called terminal ductal lobular units, are the sites where most human breast cancers rise. ... It is possible that some of these epigenetic changes also explain why the number of TEBs generally, but not always, correlates with breast cancer risk. (5)

Returning to previously-posted materials:

*************

Some studies have found that, with high soy intake, estrogen metabolism is favorably altered and menstrual cycle length increased; however, the impact of these changes on breast cancer risk is uncertain. Considerable enthusiasm remains for the possibility that soyfood intake contributes to the low breast cancer rate in Asia but increasingly it appears that childhood and/or adolescence is the critical period of exposure. This hypothesis, which is supported by both epidemiologic and animal data, is consistent with the mounting evidence that early life events greatly impact breast cancer risk ...

In addition to the potential protective effects, some data suggest that isoflavones could promote breast cancer. In vitro, genistein stimulates the growth of estrogen-sensitive mammary cancer cells, and in ovariectomized athymic mice, dietary genistein and genistin stimulate the growth of existing estrogen-sensitive mammary tumors. Consequently, in recent years, the estrogen-like effects of isoflavones have raised concerns that soyfoods are contraindicated for women at high risk of breast cancer and breast cancer patients with estrogen-sensitive tumors — approximately two-thirds of women with postmenopausal breast cancer are in this category. Numerous review articles and commentaries have been published on this topic.(6)

Soy phytoestrogens may also promote endometrial hyperplasia, another estrogen-dependent phenomenon:

Three hundred seventy-six postmenopausal healthy women, all with intact uterus ... were distributed in two different groups using randomized criteria: group A (n = 179) patients received soy tablets (150 mg of isoflavones per day) for 5 years; group B (n = 197) patients received identical appearing placebo tablets for 5 years. ... Two hundred ninety-eight women completed the 5-year treatment. No cases of malignancy were detected during biopsy. Seventy percent of women undergoing treatment with soy phytoestrogens had an endometrium classified as atrophic or nonassessable versus 81% receiving placebo. The occurrence of endometrial hyperplasia was significantly higher in group A (3.37% vs. 0%). CONCLUSION(S): Long-term treatment (up to 5 years) with soy phytoestrogens was associated with an increased occurrence of endometrial hyperplasia. These findings call into question the long-term safety of phytoestrogens with regard to the endometrium.(13)

I submit, then, that based on the experimental design problems (administration to sexually immature animals and known interspecies differences between mice and (wo)man in resveratrol biotransformation) and the biphasic and ambiguous effects of phytoestrogens in human epidemiology, experiments examining resveratrol's effects in hormone-dependent cancer models provide very little confidence that resveratrol will treat or reduce the incidence of prostate or breast cancer, and indeed might even raise the specter of a cancer risk of resveratrol supplementation in mature humans, and especially in males.
************

The importance of this new, CR-versus-resveratrol study (7) is that it is the first and only study to last for most of the natural lifespan of the animal, and the only one that assesses the effects of resveratol under conditions relevant to anyone that doesn't live on an unremediated Superfund site; and it found, again, that

unlike CR, resveratrol did not ... [cause] decrease in spontaneous tumors at the time of sacrifice [30 months -- about 80 human years -MR]. In particular, spontaneous liver tumors were abundant in mice fed the control diet or resveratrol, but rare in CR mice.(7)

"Long-lived F1 hybrid mice" were used in the study. Are these particular "hybrid" mice similar, or substantially different, from mice used in other similar studies?

As noted above, in many in vivo cases, they quite intentionally lived short- lived mutants -- again, of little relevance to normal, healthy humans. And in the other studies, the animals were subjected to intentionally hideous conditions, and in any case the previous experiments have been so short that we really don't have a good idea as to whether the mice were properly cared-for in the first place, whereas Weindruch has a thirty year record of raising some of the healthiest control mice in biogerontology.

It seems increasingly reasonable to ask why the long-promised results lifespan studies in normal, nonobese mice from Sinclair's group (8) still have still not been released, a year and a half on (emphasis mine):

Cohorts of middle-aged (one-year-old) male C57BL/6NIA mice were provided with either a standard diet (SD) or an otherwise equivalent high-calorie diet (60% of calories from fat, HC) for the remainder of their lives. To each of the diets, we added resveratrol at two concentrations ... After 6 months of treatment, there was a clear trend towards increased survival and insulin sensitivity. Because the effects were more prominent in the higher dose (22.4 0.4 mg kg-1 day-1, [High-Calorie, High-Resveratrol group], we initially focused our resources on this [High-Calorie, High-Resveratrol group])group and present the results of those analyses herein. [i]Analyses of the other groups will be presented at a later date.(8)

Silence, it seems, so far remains golden ...

-Michael

References
1. Whitsett TG Jr, Lamartiniere CA.
Genistein and resveratrol: mammary cancer chemoprevention and mechanisms of action in the rat.
Expert Rev Anticancer Ther. 2006 Dec;6(12):1699-706. Review.
PMID: 17181483 [PubMed - indexed for MEDLINE]

2. Harper CE, Patel BB, Wang J, Arabshahi A, Eltoum IA, Lamartiniere CA.
Resveratrol suppresses prostate cancer progression in transgenic mice.
Carcinogenesis. 2007 Sep;28(9):1946-53. Epub 2007 Aug 3.
PMID: 17675339 [PubMed - in process]

3. Mentor-Marcel R, Lamartiniere CA, Eltoum IE, Greenberg NM, Elgavish A.
Genistein in the diet reduces the incidence of poorly differentiated prostatic adenocarcinoma in transgenic mice (TRAMP).
Cancer Res. 2001 Sep 15;61(18):6777-82.
PMID: 11559550 [PubMed - indexed for MEDLINE]

4. Sacks FM, Lichtenstein A, Van Horn L, Harris W, Kris-Etherton P, Winston M; American Heart Association Nutrition Committee.
Soy protein, isoflavones, and cardiovascular health: an American Heart Association Science Advisory for professionals from the Nutrition Committee.
Circulation. 2006 Feb 21;113(7):1034-44. Epub 2006 Jan 17.
PMID: 16418439 [PubMed - indexed for MEDLINE]

5. Hilakivi-Clarke L.
Nutritional modulation of terminal end buds: its relevance to breast cancer prevention.
Curr Cancer Drug Targets. 2007 Aug;7(5):465-74. Review.
PMID: 17691906 [PubMed - indexed for MEDLINE]

6. Messina M, McCaskill-Stevens W, Lampe JW.
Addressing the soy and breast cancer relationship: review, commentary, and workshop proceedings.
J Natl Cancer Inst. 2006 Sep 20;98(18):1275-84. Review.
PMID: 16985246 [PubMed - indexed for MEDLINE]

7. Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch R, Prolla TA.
A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.
PLoS ONE. 2008 Jun 4;3(6):e2264.
PMID: 18523577 [PubMed - in process]

8. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA.
Resveratrol improves health and survival of mice on a high-calorie diet.
Nature. 2006 Nov 16;444(7117):337-42. Epub 2006 Nov 1.
PMID: 17086191 [PubMed - indexed for MEDLINE]

[sUper GeNius]

QUOTE
Experts said that one of the two trials, being conducted by Dr. Weindruch, was at last showing clear evidence that calorically restricted monkeys were outliving the control animals.

But no such effect is apparent in the other trial, being conducted at the National Institutes of Health.


Any comment. 50% rate of success in higher primates?

[inawe]

Another flunking:

Nutr Cancer. 2007;57(2):194-200.
Null effect of dietary restriction on prostate carcinogenesis in the Wistar-Unilever rat.McCormick DL, Johnson WD, Haryu TM, Bosland MC, Lubet RA, Steele VE.
Life Sciences Group, IIT Research Institute, Chicago, IL 60616, USA. dmccormick@iitri.org

"The results of the present study do not support the hypothesis that prostate carcinogenesis can be prevented by reducing caloric intake.
Reducing mean body weight by up to 25% through chronic dietary restriction has no effect on the induction of prostate cancers in the
Wistar-Unilever rat model."

PMID: 17571953 [PubMed - indexed for MEDLINE]

[Michael]

All:

Experts said that one of the two trials, being conducted by Dr. Weindruch, was at last showing clear evidence that calorically restricted monkeys were outliving the control animals.

But no such effect is apparent in the other trial, being conducted at the National Institutes of Health.

Any comment. 50% rate of success in higher primates?

Plagiarizing myself again...

There are actually THREE primate "CR" studies going on, with preliminary success in 2, and it's those 2 studies -- Donald Ingram's at Johns Hopkins & Richard Weindruch's at University of Wisconsin-Madison -- that are actually studies of CR per se -- ie, studies in which the effects of simple obesity are ruled out by slightly restricting the "ad libitum (AL)" animals (in rodents, this means that the "AL" group is actually fedd 10-20% less than they would if allowed to eat to their furr-encased little hearts' content, with the CR group then further restricted BEYOND this "AL" baseline).

The "failed" primate "CR" study under discussion (1), headed by Barbara Hansen at the University of Maryland-Baltimore, was NOT "real" CR in this sense, but a "weight-clamping" study. Ie, the AL group was genuinely eating all that it wanted, & the "CR" group was given enough food to maintain their adult weight rather than become obese.

Hence, (1) tells us only what we already know about the dangers of obesity & NIDDM, & little to nothing re: the effects of full-blown CR (ie active REDUCTION in Caloric intake) on AGING (as opposed to mortality merely "associated with the prevention of hyperinsulinemia and the mitigation of age-related disease") in primates generally or humans specifically; & it's only mildly surprising (even laying statistics aside for the moment) that "The oldest monkey was a diabetic female (AL) that lived to be 40 years of age."

(3) points out that the uselessness of the weight-clamping study (1) as evidence on the translatability of CR goes far deeper, as it was riddled with methodological flaws and inaccurate reporting:

In general, Bodkin and colleagues concluded that DR increases average age at death associated with prevention of hyperinsulinemia and the mitigation of other age-related diseases and disease markers. Caution must be exercised to avoid over-interpretation of these findings. We contend that their results do not provide sufficient evidence to support the conclusion that DR exerts the same widespread beneficial effects in nonhuman primates (and by genetic similarity, human primates) as has been extensively reported in rodents ... The preliminary nature of these findings is dictated by methodological issues, including study design, subject characteristics, and statistical methodology, any of which may limit the generalizability of these findings. Of significant concern is that several experimental controls typically used in rodent DR studies were not applied in the Bodkin and colleagues study.

First, only 8 of the total 117 rhesus monkeys were in the DR group, and only 3 deaths occurred in this experimental group. This is an extremely small sample size for any mortality study. The typical rodent longevity study would include 30–40 animals per treatment group. Second, while the number of monkeys in the ad libitum (control) group is sufficiently large (n = 109), control and DR monkeys did not enter the study at the same time, nor were they randomly assigned to either the control or DR groups.

It is apparent that the study by Bodkin and colleagues was not designed at the outset to address the question to which the conclusions are directed, specifically the effects of DR on aging and age-related disease. The authors state that all subjects were part of a longitudinal study on aging, obesity, and spontaneous diabetes. Monkeys described in this paper were part of a series of individual experiments rather than a single focused investigation of DR and aging. … environmental and procedural variables would also need to be controlled. Specifically, all monkeys would need to be housed in the same type cage, in the same or similar vivaria, and decisions regarding treatment of disease and euthanasia would have to be standardized.

This type of environmental control was not described by Bodkin and colleagues. Another methodological issue is that the paper does not make clear how many animals had a known date of birth and therefore a reliable age at death [!]. The paper states explicitly that all animals had a recorded age (p. 213). The practice of recording an estimated age when the specific birth date is not known, particularly for wild-caught monkeys, is common in primate research. ... Certainly these factors contribute to significant variability in estimated ages thereby negatively impacting any conclusions about differences in life span and age at onset of disease.

Differences in the diet fed to monkey in the study could have led to another methodological problem. Unlike most rodent DR studies in which diets for control and DR groups are highly controlled, it is apparent that monkeys in the Bodkin and colleagues study did not all consume the same diet. Standard monkey chow (17% protein, 70% carbohydrate, and 13% fat) was fed to most animals in the study. However, 15% (n = 16, p. 213) of the AL monkeys were fed a liquid diet different in composition (14% protein, 55% carbohydrate, and 31% fat) most notably over twice the amount of fat compared to the standard diet. [& NB the fact that a ‘liquid lunch’ often has a higher GI than a solid one – perhaps contributing to diabetes -MR] .

The 8 DR monkeys were brought into the larger colony as a separate cohort of adult monkeys already on a weight stabilization protocol designed to maintain a normal adult body weight. … The authors point out that body weight (10–11 kg) and percent fat (17%–24%) for the DR group was comparable to that of a normal, lean monkey (p. 213). ... The reader does not know what amount of food was provided to each monkey … and no information on calorie intake is given for AL controls. Body weights on entry into the study were comparable in the AL group (Table 1, p. 214); however, data on weight or fat percentage at the end of the study is not provided. … Previous publications from this laboratory suggest a body weight range of 15.4 to 19.5 kg, and fat percentages ranging from 20% to 48% would be expected in the AL-fed monkeys that were featured in this report. ... This concern calls to question whether monkeys in the AL group represented a relevant group for comparison to the 8 monkeys in the DR cohort.

… the animals' age of entry into the study is quite varied, ranging from 4 years in the AL normal group to 29 years in the AL diabetic group. … [A]ge is an important covariate strongly related to mortality and, in many cases, age is related to the nonproportionality of many other risk factors. Thus, ignoring age and accepting the proportionality assumption can lead to conflicting and nonconclusive results. … The 95% confidence intervals for the hazard ratios presented in Table 2 show that there are essentially no statistical differences in these ratios from the no-effect ratio reference values of 1.0. Also, many of the confidence intervals are quite large, ... The only significant result was the DR group versus the AL hyperinsulinemic group, which had the widest confidence interval of all those reported in Table 2. Most importantly, using the group with the largest sample size, AL normal, as the reference group resulted in no evidence of statistical significance at all.

In the abstract of the paper, the authors state the following: "Compared with the DR monkeys, the AL monkeys had a 2.6-fold increased risk of death." Although, in the body of the text, the authors acknowledge that this comparison was not statistically significant, they continue to make similar statements throughout the paper [!]. Finally, Table 3 shows that there are no differences in the risk of mortality between the DR and AL groups when other characteristics or covariates are entered into the regression model. Thus, the statistical results presented by Bodkin and colleagues do not appear to support any finding of differences in the risk of mortality between the different dietary groups. If anything, the authors' results reflect the unplanned or convenient nature of the study population characterized by the small sample size in the DR group and the overall heterogeneity of the animals in the study.

Further concerns not addressed by Bodkin and colleagues involve the issue of censoring monkeys from statistical analyses. Are the censoring patterns the same in the different study groups? If not, then any informative censoring might be related to the outcome. (3)

So the title "Effects of long-term diet restriction on aging and longevity in primates remain uncertain" is of course true -- but it's really pointing out that the reason for the ongoing uncertainty lies in the fact taht Hansen's group has not provided us with any new evidence.
As to how the "real" CR animals are doing (the Ingram/Roth and Weindruch studies will be ongoing for some time, with proper controls ):

Previous reports from our laboratory have suggested that morbidity, in particular neoplastic disease (Black et al., 2000), and perhaps even mortality (Roth et al., 1999) are reduced in monkeys on CR. Currently, the proportion of rhesus and squirrel monkeys that have died in the CR cohorts is about one half of that observed in the controls. Specifically, for squirrel monkeys 33% of the initial CR cohort has died compared with 54% in the group of age-matched controls. In rhesus monkeys, the percentages are 13 and 23% for CR and controls, respectively (M.A.L. unpublished data). Though preliminary, these emerging data suggest that CR will, as reported consistently in rodents, extend lifespan and reduce morbidity in nonhuman primates. (2)

That was a summary from 2002. There've been more supportive developments since -- more benefits in specific diseases (like the Alzheimer's study you mention, and another in model Parkinson's), further divergence in incidence of disease and in mortality, a possible single super-extreme survivor in the CR group -- but I can't be arsed to go dig it up . This is all the more remarkable since, on various grounds, it appears that the monkeys are very minimally CRed indeed (4).


-Michael

1: Bodkin NL, Alexander TM, Ortmeyer HK, Johnson E, Hansen BC. Mortality and morbidity in laboratory-maintained Rhesus monkeys and effects of long-term dietary restriction. J Gerontol A Biol Sci Med Sci. 2003 Mar;58(3):212-9.
PMID: 12634286 [PubMed - indexed for MEDLINE]

2. Lane MA, Mattison J, Ingram DK, Roth GS.
Caloric restriction and aging in primates: Relevance to humans and possible CR mimetics. Microsc Res Tech. 2002 Nov 15;59(4):335-8. Review.
PMID: 12424798 [PubMed - indexed for MEDLINE]

3. Lane MA, Mattison JA, Roth GS, Brant LJ, Ingram DK.
Effects of long-term diet restriction on aging and longevity in
primates remain uncertain.
J Gerontol A Biol Sci Med Sci. 2004 May;59(5):B405-7. No abstract
available.
PMID: 15123747 [PubMed - in process]

4. Rae MJ.
You don't need a weatherman: famines, evolution, and intervention into aging.
AGE. 2006 March;28(1):93-109.

Edited by Michael, 09 February 2009 - 09:47 PM.

[Anthony_Loera]

First off:
Pinning an article that has less than 100 views is something I am not used seeing on this board. It appears this opinion has garnered the attention of the board admins here, and appears to be very important. So much so that it deserves a permanent spot, very interesting.

So let's look at this, from what I gather we are talking about adiscussion regarding low dose of resveratrol doing nothing for cancer, as the quote comes from the PLoS ONE website:
http://www.plosone.o...al.pone.0002264

Micheal makes an argument below based on this study:
====================================
hmm:

And yet RSV does appear to fight cancer at higher dosage levels, does it not?

Michael:

Yes -- under totally artificial conditions wink.gif. RSV has been shown to inhibit (a) in vitro carcinogenesis, which can obviously be of zero evidential value on whether something really happens in the real world (although such studies are often helpful in elucidating the mechanisms whereby an effect already observed in vivo occurs); (b) cancer incidence or progression induced or promoted in vivo by nasty chemical carcinogens, in which case you're mostly looking at a stupid antioxidant, drug-detoxifying, or sometimes (eg in the colon) a cyclooxygenase-inhibiting effect, none of which has anything to do with prevention of "normal," age-related cancer (which primarily results from mutations induced by endogenous DNA damage during mitosis); or ( c ) in vivo in estrogen-sensitive cancer models (Transgenic Adenocarcinoma Mouse Prostate (TRAMP) mice, estrogen-sensitive transplanted human prostate or breast cancer lines, etc -- eg, (1,2)), which likely results from resveratrol's phytoestrogen properties -- which is risky business.

The alleged benefits even of soy phytoestrogens, which are much better-studied in humans (because we have done more clinical trials and, more importantly, have a lot of prospective epidemiology) remain highly ambiguous.

====================================

Good argument! But I don't agree with it.

The remainder of the first post talks about phytoestrogens, and similarities with resveratrol. So Mike's opinion, is that resveratrol works like other phytoestrogens found, and will not work against cancer. Do I have this right?

I presume I do.

Mike, your opinion piece is good, and I appreciate the other side of the argument. But just like you believe "in vitro" studies can obviously be of zero evidential value, I have to state that I believe your opinion, is interesting, but may qualify to be of zero evidential value as well since higher dosage results are not presented and you are posting your views based on different phytoestrogens.

Then again, maybe I am confused.

Which of the items below are you arguing, as it seemss I may need some clarity... Pick one or more from the choices below, or make your own bullet points:

1- Resveratrol does not provide CR at low doses
2- CR does not help with cancer
3- low dose of resveratrol does not help with cancer
4- You have determined that high dose of resveratrol will not work becasue a low dose did not work, and the similarities of other phytoestrogens.
5- All of the above
6- Primates studies are faulty
7- Resveratrol studies are faulty
8- Phytestogens are all the same...and taking a large amount of soy is the same as taking a large amount of resveratrol...

Uhmm... Just clean it up a bit for me. For now, I consider it an opinion piece with links to studies that (for the most part) don't talk about resveratrol in relation to your selected post (and pinned) topic.

It's easy really, just convince me with resveratrol studies. If you do, I may just change my business again.

Thanks
A

Edited by Anthony_Loera, 06 June 2008 - 10:13 PM.

[Shepard]

First off:
Pinning an article that has less than 100 views is something I am not used seeing on this board. It appears this opinion has garnered the attention of the board admins here, and appears to be very important. So much so that it deserves a permanent spot, very interesting.

I pinned it for the time being so that it gets the attention it deserves. Michael's posting are among the highest quality I've seen the Health section. Depending on the quality of the discussion that occurs will determine whether or not it stays pinned.

[maxwatt]

First off:
Pinning an article that has less than 100 views is something I am not used seeing on this board. It appears this opinion has garnered the attention of the board admins here, and appears to be very important. So much so that it deserves a permanent spot, very interesting.

I pinned it for the time being so that it gets the attention it deserves. Michael's posting are among the highest quality I've seen the Health section. Depending on the quality of the discussion that occurs will determine whether or not it stays pinned.

Some quick thoughts; I haven't the time to properly reference everything, but....

Resveratrol and cancer: I remarked HERE on a paper showing resveratrol inhibits the wnt pathway, which should inhibit some forms of cancer, including breast cancer, I think in this THREAD.

The article Michael is quoting, HERE states:

We note that unlike CR, resveratrol did not reduce circulating IGF-1 levels (Figure 2B), and there was also no decrease in spontaneous tumors at the time of sacrifice (Supplemental Table S2).

However, folic acid does reduce IGF-1 levels, (see LINK above) activating the genes turned on by CR that resveratrol does not. So it would be interesting to evaluate resveratrol plus folic acid versus CR. I am adding folic acid to my daily resveratrol dose to attempt to mimic more fully the gene expression induced by resveratrol.

Mice are not miniature human beings. Lab mice all get tumors, usually dying by the age of two as a result. Most humans do not; we have much better cellular repair mechanism than mice. That resveratrol in a low dose had no effect on tumorogenesis in mice says nothing about a life extending in humans one way or the other, but it does raise questions about the cancer-causing patways in mice, and how CR regulates them. Perhaps CR turn on repair mechanisms in mice that humans already have without CR, thogh it is unlikely to be that simple.

[Brainbox]

Phytestogens are all the same...and taking a large amount of soy is the same as taking a large amount of resveratrol...

As far as I understand, it's not primarily the similarity of the studied substances that is addresses by Micheal, but the similarity in study designs by using studies of similar substances. And the analogy between promising study results in artificial environments versus less promising or even possible detrimental results in real-life situations. He's trying to extrapolate the still incomplete resveratrol results along the line of the better studied soy phytoestrogens to show the probable flaws that occur while extrapolating the results of limited studies in animal models or even in-vitro artificial models to real life human proportions. At least that's how I read Micheal's contribution. At least it seems that Micheal's reasoning is a bit more subtle than the quote above is suggesting.

It seems increasingly reasonable to ask why the long-promised results lifespan studies in normal, nonobese mice from Sinclair's group (8) still have still not been released, a year and a half on (emphasis mine):

Cohorts of middle-aged (one-year-old) male C57BL/6NIA mice were provided with either a standard diet (SD) or an otherwise equivalent high-calorie diet (60% of calories from fat, HC) for the remainder of their lives. To each of the diets, we added resveratrol at two concentrations ... After 6 months of treatment, there was a clear trend towards increased survival and insulin sensitivity. Because the effects were more prominent in the higher dose (22.4 0.4 mg kg-1 day-1, [High-Calorie, High-Resveratrol group], we initially focused our resources on this [[i]High-Calorie, High-Resveratrol group])group and present the results of those analyses herein. Analyses of the other groups will be presented at a later date.(8)

Silence, it seems, so far remains golden ...

Bingo! The almost forgotten 1000$ question.

Edited by brainbox, 07 June 2008 - 07:14 AM.

[maxwatt]

......snip...

It seems increasingly reasonable to ask why the long-promised results lifespan studies in normal, nonobese mice from Sinclair's group (8) still have still not been released, a year and a half on (emphasis mine):

Cohorts of middle-aged (one-year-old) male C57BL/6NIA mice were provided with either a standard diet (SD) or an otherwise equivalent high-calorie diet (60% of calories from fat, HC) for the remainder of their lives. To each of the diets, we added resveratrol at two concentrations ... After 6 months of treatment, there was a clear trend towards increased survival and insulin sensitivity. Because the effects were more prominent in the higher dose (22.4 0.4 mg kg-1 day-1, [High-Calorie, High-Resveratrol group], we initially focused our resources on this [[i]High-Calorie, High-Resveratrol group])group and present the results of those analyses herein. Analyses of the other groups will be presented at a later date.(8)

Silence, it seems, so far remains golden ...

Bingo! The almost forgotten 1000$ question.

I suspect that the healthy-looking resveratrol fed mice died of cancer the same as the sickly looking control group. Some cancers respond to the wnt pathway which resveratrol inhibits. Others do not, because additionally they affect expression of the hedgehog pathway which resveratrol does not inhibit. Something more than resveratrol is needed to achieve life extension in mice. I suspect this is true in humans, but I am convinced resveratrol is a good start.

Mol Nutr Food Res. 2008 May 26. [Epub ahead of print] Links
Low concentrations of resveratrol inhibit Wnt signal throughput in colon-derived cells: Implications for colon cancer prevention.Hope C, Planutis K, Planutiene M, Moyer MP, Johal KS, Woo J, Santoso C, Hanson JA, Holcombe RF.
Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. Fax: 714-456-2242.

Resveratrol is a bioflavonoid which is known to inhibit cell proliferation and induce apoptosis in cancer cell lines at concentrations above 50 muM. It also has colon cancer prevention activity in mouse models and possibly in humans. We have examined the effects of low concentrations of resveratrol on a specific signaling pathway, the Wnt pathway, which is activated in over 85% of sporadic colon cancers. Two colon cancer (HT29 and RKO) and one normal mucosa-derived (NCM460) cell lines were utilized. Cell proliferation was not affected by resveratrol at less, not double equals40 muM for HT29 and NCM460 and <20 muM for RKO though Wnt signal throughput, as measured by a reporter construct, was reduced in RKO and NCM460 at concentrations as low as 10 muM (p < 0.001). This effect was most easily appreciated following Wnt pathway stimulation with Wnt3a conditioned medium and LEF1 or LEF1/beta-catenin transfection. Resveratrol did not inhibit Wnt throughput in mutationally activated HT29. Low concentrations of resveratrol significantly decreased the amount and proportion of beta-catenin in the nucleus in RKO (p = 0.002) and reduced the expression of lgs and pygoI, regulators of beta-catenin localization, in all cells lines. Thus, at low concentrations, in the absence of effects on cell proliferation, resveratrol significantly inhibits Wnt signaling in colon-derived cells which do not have a basally activated Wnt pathway. This inhibitory effect may be due in part to regulation of intracellular beta-catenin localization.

PMID: 18504708

edited for clarity and speling

Edited by maxwatt, 07 June 2008 - 01:12 PM.

[kismet]

If Michael is right and res at low doses (as shown in the discussed study) and high doses does not fight cancer, it is very unlikely that Sinclair's group would have shown any life extension from res.
Hence, we still can only guess if res might slow intrinsic aging in a rodent model (if cancer was excluded) or in humans...
So to show if res works one would need to compare e.g. GH knockout mice + res or CR + res (ok, that may be pointless if res is indeed a CR mimetic) against GH knockout respectively CR mice alone? [i.e. reducing cancer incidence to focus more on other aspects of aging]

[Hedgehog]

I suspect that the healthy-looking resveratrol fed mice died of cancer the same as the sickly looking control group. Some cancers respond to the wnt pathway which resveratrol inhibits. Others do not, because additionally they affect expression of the hedgehog pathway which resveratrol does not inhibit. Something more than resveratrol is needed to achieve life extension in mice. I suspect this is true in humans, but I am convinced resveratrol is a good start.

Mol Nutr Food Res. 2008 May 26. [Epub ahead of print] Links
Low concentrations of resveratrol inhibit Wnt signal throughput in colon-derived cells: Implications for colon cancer prevention.Hope C, Planutis K, Planutiene M, Moyer MP, Johal KS, Woo J, Santoso C, Hanson JA, Holcombe RF.
Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. Fax: 714-456-2242.

Resveratrol is a bioflavonoid which is known to inhibit cell proliferation and induce apoptosis in cancer cell lines at concentrations above 50 muM. It also has colon cancer prevention activity in mouse models and possibly in humans. We have examined the effects of low concentrations of resveratrol on a specific signaling pathway, the Wnt pathway, which is activated in over 85% of sporadic colon cancers. Two colon cancer (HT29 and RKO) and one normal mucosa-derived (NCM460) cell lines were utilized. Cell proliferation was not affected by resveratrol at less, not double equals40 muM for HT29 and NCM460 and <20 muM for RKO though Wnt signal throughput, as measured by a reporter construct, was reduced in RKO and NCM460 at concentrations as low as 10 muM (p < 0.001). This effect was most easily appreciated following Wnt pathway stimulation with Wnt3a conditioned medium and LEF1 or LEF1/beta-catenin transfection. Resveratrol did not inhibit Wnt throughput in mutationally activated HT29. Low concentrations of resveratrol significantly decreased the amount and proportion of beta-catenin in the nucleus in RKO (p = 0.002) and reduced the expression of lgs and pygoI, regulators of beta-catenin localization, in all cells lines. Thus, at low concentrations, in the absence of effects on cell proliferation, resveratrol significantly inhibits Wnt signaling in colon-derived cells which do not have a basally activated Wnt pathway. This inhibitory effect may be due in part to regulation of intracellular beta-catenin localization.

PMID: 18504708

edited for clarity and speling

Colon cancer and the Wnt pathway very closely related.... Maybe a slow release resveratrol tablet. Colon cancer would be an ideal candidate for resveratrol since it would be easy to target. Wnt also a key regulator of metastasis. I would guess resveratrol might also help prevent colon cancer....

[Hedgehog]

Colon cancer and the Wnt pathway very closely related.... Maybe a slow release resveratrol tablet. Colon cancer would be an ideal candidate for resveratrol since it would be easy to target. Wnt also a key regulator of metastasis. I would guess resveratrol might also help prevent colon cancer....

Oct. 24, 2006 -- People who drink three or more glasses of red wine a week are less likely to get the abnormal colon growths that can lead to cancer, according to a new study.

The study was done by Joseph Anderson, MD, and colleagues at New York's Stony Brook University. It was presented at the American College of Gastroenterology's annual scientific meeting in Las Vegas.

The study looked at the habits of more than 1,700 people who were, on average, in their late 50s. It also checked for the incidence of abnormal colon growths, including polyps.

The researchers found that 3% of red wine drinkers had such abnormal growths, compared with nearly 9% of white wine drinkers and almost 10% of teetotalers.



http://www.webmd.com...vs-colon-cancer



While moderate wine drinkers -- those who drank one to eight glasses a week -- were 63% less likely to develop colon cancer, heavier wine drinking was not protective, Sethi says. Drinking beer appeared to have no effect on colon cancer risk, the study showed.


http://www.webmd.com...lon-cancer-risk


They found that drinking red wine significantly reduced the risk of colorectal neoplasia by 68 percent, but drinking white wine did not. Researchers suspect that higher concentrations of the compound resveratrol in red wine may provide a protective effect against colon cancer.

The research highlights the potential role of red wine in chemoprevention of colon cancer, but when it comes to proven prevention strategies, doctors say screening for colorectal cancer remains essential and is the most proven preventative measure that individuals can use to reduce their risk of developing this disease.


http://www.consumera...wine_colon.html

[inawe]

Michael's posting are among the highest quality I've seen the Health section.

That's GREAT!
I'm trying to learn biology in order to understand how things inside me work and make them better. So I was excited to learn of this guy
Michael who knows the stuff and will be able to explain things to me.
What's under discussion is not just Resveratrol (RSV) but a comparison of RSV and Calorie Restriction (CR).
I keep reading that "CR is the only intervention proven to extend life". Because of that, other interventions are compared with CR. This is a
mistake because of the CR fundamentalist. To compare anything else to CR to them, is like comparing anybody else to Mohammed, to a
fundamentalist Muslim.
Couldn't find an explanation, at the biological molecular level, of how CR is extending life. According to this latest Weindruch
paper, overexpression of SIRT1 by CR is out. So I'm anxiously waiting for Michael to explain how CR extends life.
As for eating, we have obesity on one extreme and anorexia on the other. Both extremes are very bad. CR is somewhere in between, but
where? I eat 1700 cal/day and exercise for 600 cal/day. The balance is 1100 cal/day. Is that all right? I'm happy with my 14% body fat.
Probably this doesn't qualify as CR, so be it.
As for RSV, I take 1.5-2 gr/day for about a year now. I feel better than before I started taking that much RSV. I keep reading papers to see
if the RSV could hurt me. I didn't find any so I'll keep taking RSV. Even if it flunks ... Hey, in Michael's presentation it was the first
time I saw the word flunk in connection to whatever a supplement is doing.

[niner]

Hedgehog's post about the red wine epidemiology with respect to colon cancer is a nice bit of evidence. It strongly suggests that at least something in red wine is active. Whether that something is resveratrol or not is yet to be nailed down, though it's a good candidate. The paper about the Wnt pathway talks about in vitro levels of 10 uM or more. That is hardly a low dose in humans. To achieve a plasma level of 10uM in free resveratrol would require a dose of perhaps 20 grams, based on the Boocock study of high dose res pharmacokinetics. And that was only Wnt pathway inhibition. Getting the cancer cells to stop dividing required 20 to 40 uM. This does not mean that there isn't a concentrating mechanism going on somewhere, or that intestinal epithelia are not a special case because the resveratrol is sitting there.

I appreciate Michael's posts. He really knows his poop, although he does seem a bit religious about CR. The data is there on CR, whereas the data on supplements is weaker. Michael is a good counterpoint to the over the top supplement hype that is out there.

[Hedgehog]

Hedgehog's post about the red wine epidemiology with respect to colon cancer is a nice bit of evidence. It strongly suggests that at least something in red wine is active. Whether that something is resveratrol or not is yet to be nailed down, though it's a good candidate. The paper about the Wnt pathway talks about in vitro levels of 10 uM or more. That is hardly a low dose in humans. To achieve a plasma level of 10uM in free resveratrol would require a dose of perhaps 20 grams, based on the Boocock study of high dose res pharmacokinetics. And that was only Wnt pathway inhibition. Getting the cancer cells to stop dividing required 20 to 40 uM. This does not mean that there isn't a concentrating mechanism going on somewhere, or that intestinal epithelia are not a special case because the resveratrol is sitting there.

I appreciate Michael's posts. He really knows his poop, although he does seem a bit religious about CR. The data is there on CR, whereas the data on supplements is weaker. Michael is a good counterpoint to the over the top supplement hype that is out there.

I see it as more like a preventative type of molecule for cancer not really a cancer killer molecule. It is probably too hard to get high enough concentrations (in-vivo) to affect the correct proteins like Bcl2. (you MIGHT be able to for cancers such as stomach or colon cancer)


Bcl2--->(probably the mechanism for resveratrol apoptosis mechanism @ high concentrations).
Wnt-->(low concentrations might prevent cancers such as colon or stomach cancer) However, can induce apoptosis but @ high concentrations. Wnt pathway is a morphogenic pathway. IE different amounts of pathway activation/inhibition give different results such as apoptosis or cell division.

http://aacrmeetingab...ract/2006/3/A37

Edited by Hedgehog, 07 June 2008 - 10:05 PM.

[krillin]

It strongly suggests that at least something in red wine is active. Whether that something is resveratrol or not is yet to be nailed down, though it's a good candidate.

OPCs are more likely. Wine only has as much resveratrol as Ortho-Core.

Nutr Cancer. 2004;49(1):81-8.
Chemoprevention of colorectal cancer by grape seed proanthocyanidin is accompanied by a decrease in proliferation and increase in apoptosis.
Nomoto H, Iigo M, Hamada H, Kojima S, Tsuda H.
Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.

Effects of proanthocyanidin (PA), procyanidin B-2 (B-2), and epigallocatechin gallate (EGCG) on azoxymethane (AOM)-induced colonic preneoplastic aberrant crypt foci (ACF) formation were investigated using F344 rats. The numbers of total ACF in rats treated with 0.002% PA and 0.05% B-2 were significantly decreased compared with the AOM alone group (control). Cell proliferation in the colon, as shown by proliferating cells nuclear antigen (PCNA), was also reduced in those treatments. The single-stranded DNA (ssDNA) labeling index, a marker for apoptosis, was significantly increased in 0.002% PA and 0.05% B-2 groups compared with control. Moreover, the numbers of CD11b/c+ cells (macrophages) and NKR-P1A+ cells (NK cells) in the all groups were significantly increased compared with control. In an in vitro study using rat colon cancer cell line RCN-9, PA, especially 5-10mer of PA (PA5/10), strong growth inhibition was shown. PA5/10 caused the most remarkable apoptosis as cleared by FACS analysis. These cells showed significantly increased caspase-3 activity. The results would suggest that the PA, especially PA5/10, might strongly enhance caspase-3 activity and cause apoptosis in cancer cells. PA at fairly low doses in the long term might serve as an effective means for preventing colon carcinogenesis.

PMID: 15456639

[missminni]

All:

Yes -- under totally artificial conditions wink.gif. RSV has been shown to inhibit (a) in vitro carcinogenesis, which can obviously be of zero evidential value on whether something really happens in the real world

It seems increasingly reasonable to ask why the long-promised results lifespan studies in normal, nonobese mice from Sinclair's group (8) still have still not been released, a year and a half on (emphasis mine):

Cohorts of middle-aged (one-year-old) male C57BL/6NIA mice were provided with either a standard diet (SD) or an otherwise equivalent high-calorie diet (60% of calories from fat, HC) for the remainder of their lives. To each of the diets, we added resveratrol at two concentrations ... After 6 months of treatment, there was a clear trend towards increased survival and insulin sensitivity. Because the effects were more prominent in the higher dose (22.4 0.4 mg kg-1 day-1, [High-Calorie, High-Resveratrol group], we initially focused our resources on this [High-Calorie, High-Resveratrol group])group and present the results of those analyses herein. [i]Analyses of the other groups will be presented at a later date.(8)

Silence, it seems, so far remains golden ...

-Michael

In the REAL world,
Res cured my 9 year old female american bulldog of mammary cancer. I posted about it in the Resveratrol for dogs forum. Her biopsy report was dire. The vet said she'd be dead in 6 months if she lasted that long. The cancer was in her lymph glands too. I am happy to tell you 6 months later, she is very much alive and well and healthier than ever.
She's 94 lbs. I gave her between 4-6 grams a day for the first 4 months. I've since lowered her daily dose to 2 -3 g a day and I'm planning to reduce it a even more. She was a goner according to the vet, the Animal Medical Center and a veterinarian oncologist. Resveratrol worked. It did the same thing for a friends dog that had a huge malignant tumor on the outside of her tummy and after a few months of taking resveratrol, her tumor is half the size.

Both these dogs had biopsies and were examined by professionals prior to the resveratrol dosing. In both cases the doctors were amazed at their condition on their return visits. My vet is with the Animal Medical Center and she can substantiate this.

Edited by missminni, 08 June 2008 - 07:59 PM.

[Shannon Vyff]

This thread deserves being pinned, it is quite exciting and I thank Michael very much for sharing with us.

[sUper GeNius]

[font="Courier"][size=2]
In the REAL world,
Res cured my 9 year old female american bulldog of mammary cancer. I posted about it in the Resveratrol for dogs forum.
[/quote]

There's a esveratrol for dogs forum? Where?

[missminni]

In the REAL world,
Res cured my 9 year old female american bulldog of mammary cancer. I posted about it in the Resveratrol for dogs forum.

There's a esveratrol for dogs forum? Where?

It's here

[missminni]

This thread deserves being pinned, it is quite exciting and I thank Michael very much for sharing with us.

I agree but I think the title is biased. "Does Resveratrol Flunk Real World Cancer?" would be
more appropriate. In my real world, it cured it. If anyone would like to see my dogs biopsy report
I will post it and will ask the vet from Animal Medical Center to send me a copy of her examination of Minni.

[kismet]

Is it gone completely as per the biopsy?
Such a small smaple size is not convincing and 6 months are definitely not long enough to tell (isn't cancer often recurring?) - though, your account is very promising.
Take care not to kill your dog (and the evidence for reservatrol's efficacy) by ceasing the res prematurely - assuming it really helped to fight of the cancer.

[mikeinnaples]

Sorry, I must of missed something in this conversation so if I am asking a silly question so be it.


Anyways, exactly where is the research that says Resveratrol flunks v. real world cancer in humans in vivo? Can some quote something other than an opinion or post a link to the human research?

[missminni]

Is it gone completely as per the biopsy?
Such a small smaple size is not convincing and 6 months are definitely not long enough to tell (isn't cancer often recurring?) - though, your account is very promising.
Take care not to kill your dog (and the evidence for reservatrol's efficacy) by ceasing the res prematurely - assuming it really helped to fight of the cancer.

I'm not going to stop giving it to her entirely...just little less than 4-6 grams a day, but maybe I should keep it at the same dose. Thanks for pointing that out. The vet (from Bobst Animal Medical Center) was amazed at her condition. AMAZED!!
She asked very specific questions about dosage, frequency, where I got it etc. I gave her as many pubmed articles I could about it. She was
going to talk to the admin there about doing clinical trials, although it was highly unlikely since they never did trials that weren't financed by a drug company.
Below is a copy of the biopsy report. Also, she looks incredible...and she's 9 and half years old. She looks better than ever.
Even her hind legs where she had torn both cruciate ligaments the year before (forgive wrong spelling) look better...straighter.
It's very noticeable. Everyone comments on how amazing she looks. And my friends dog had a very noticeable decrease in tumor size.
She's an eleven year old dog.
P.S. I just realized the date on the biopsy is Jan 8th, so it's only 5 months....ouch. I better not decrease her dosage at all.
But the vet didn't even really expect her to last this long. He said 6 months was the most I could hope for. The vet at AMC
said she would have shown some signs of deterioration by now but its just the opposite.

Antech Diagnostics 1111 Marcus Avenue Lake Success NY 11042 Phone: 800-872-1001

Eastside Animal Hospital Client # 4132

321 E 52nd St Chart #

New York, NY 10022

Tel: 212-751-5176

Fax: 212-980-3494

Accession No. Doctor Owner Pet Name Received

NYBA01538411 M CARSON MINNIE 01/08/2008

Species Breed Sex Pet Age Reported

Canine Bulldog SF 11Y 01/17/2008 03:37 PM

Test Requested Results Reference Range Units

Biopsy

Biopsy

Microscopic Description: Sections of the 4th and 5th mammary gland

are examined on 3 slides. There is a discrete, partially

encapsulated neoplasm composed of epithelial cells that form

papillary fronds within dilated ducts. The cells have abundant

eosinophilic polyhedral cytoplasm with distinct cell margins. The

nuclei are hyperchromatic with marginated, coarsely clumped

chromatin. Most cells have prominent nucleoli. There is a moderate

mitotic index. The neoplasm is infiltrating the surrounding

connective tissue. Tumor emboli can be seen within lymphatic

vessels. The samples include lymph node. There are nests of

neoplastic cells within the subcapsular sinusoids.



Microscopic Findings: Mammary adenocarcinoma, high grade.



Comment: Survival time and disease free interval of patients with

mammary adenocarcinoma is best correlated with tumor size, degree of

local invasion, nodal or distant metastasis at the time of diagnosis

[1,2]. While this neoplasm is discrete, there is local tissue and

lymphatic vascular invasion. The lymphatic vascular invasion is a

portent of metastatic disease. The prognosis is poor.

[1] Misdorp, W, et al. Prognostic factors in canine mammary cancer.

J Natl Cancer Inst. 56:779-86, 1976.

[2] Yamagami, T, et al. Prognosis for canine malignant mammary

tumors based on TNM and histologic classification. J Vet Med Sci.

58:1079-83, 1996.



David A. Gamble, DVM, PhD, DACVP


Report Notes:

R MAMMARY 4 AND 5

Edited by missminni, 09 June 2008 - 01:25 PM.

[VictorBjoerk]

Very interesting thread, Resveratrol maybe should be used in hospices for experimentation?

[missminni]

Very interesting thread, Resveratrol maybe should be used in hospices for experimentation?

That would be interesting, but why wait for hospice? If I were diagnosed with
breast cancer or ovarian cancer, I would try Resveratrol before doing Chemo. Everyone I know who did Chemo
got cancer back within a few years anyway. At least with Res, you can take it ongoing. If only people knew,
so many lives could be saved. I think of so many people I know who died from breast cancer, and more than likely,
a simple powder mixed in their food could have saved them. I might be celebrating prematurely with my dog, but
if you could see her and the look on the vets face when she saw her, you would understand why. And not to
forget my friends dog whose tumor keeps getting smaller. These are not young dogs either.

[mikeinnaples]

From what I can read here, its pure speculation at this point that it doesn't work v. cancer in-vivo. Still waiting for some real evidence that it won't.

Why is this pinned again?

[maxwatt]

Sorry, I must of missed something in this conversation so if I am asking a silly question so be it.


Anyways, exactly where is the research that says Resveratrol flunks v. real world cancer in humans in vivo? Can some quote something other than an opinion or post a link to the human research?

Michael gave a link to the article when he started this thread.

Basically, the resveratrol-fed mice developed cancer and died without an extension of maximal life-span, unlike CR where the mice did not get cancer and lived longer.
But there were other benefits, and the doses used were low. The experiemnt should be repeated with higher doses.
Also resveratrol did not modulate IGF-1, which CR did. (FWIW, folic acid does modulate IGF-1; I've added 80 to 1600 mcg to my morning resveratrol to see if it has any effect on my insulin levels.)
Resveratrol has been shown to inhibit wnt pathway, which is anti-cancer; some studies have show benefits for colin and mammary cancers.

So the title of this thread is perhaps unwarranted and misleading. It should be "low dose resveratrol does not affect skin cancer incidence in mice."

[missminni]

Michael gave a link to the article when he started this thread.

Basically, the resveratrol-fed mice developed cancer and died without an extension of maximal life-span, unlike CR where the mice did not get cancer and lived longer.
But there were other benefits, and the doses used were low. The experiemnt should be repeated with higher doses.
Also resveratrol did not modulate IGF-1, which CR did. (FWIW, folic acid does modulate IGF-1; I've added 80 to 1600 mcg to my morning resveratrol to see if it has any effect on my insulin levels.)
Resveratrol has been shown to inhibit wnt pathway, which is anti-cancer; some studies have show benefits for colin and mammary cancers.

So the title of this thread is perhaps unwarranted and misleading. It should be "low dose resveratrol does not affect skin cancer incidence in mice."

For some reason, I was under the impression that resveratrol was primarily effective with hormonal cancers. Skin cancer isn't hormonal, is it?
Is this a contest between CR and Resveratrol? Can't they co-exist?

[maxwatt]

Michael gave a link to the article when he started this thread.

Basically, the resveratrol-fed mice developed cancer and died without an extension of maximal life-span, unlike CR where the mice did not get cancer and lived longer.
But there were other benefits, and the doses used were low. The experiemnt should be repeated with higher doses.
Also resveratrol did not modulate IGF-1, which CR did. (FWIW, folic acid does modulate IGF-1; I've added 80 to 1600 mcg to my morning resveratrol to see if it has any effect on my insulin levels.)
Resveratrol has been shown to inhibit wnt pathway, which is anti-cancer; some studies have show benefits for colin and mammary cancers.

So the title of this thread is perhaps unwarranted and misleading. It should be "low dose resveratrol does not affect skin cancer incidence in mice."

For some reason, I was under the impression that resveratrol was primarily effective with hormonal cancers. Skin cancer isn't hormonal, is it?
Is this a contest between CR and Resveratrol? Can't they co-exist?

Michael Rae practices CR,a nd has been, well, some say hostile, to any supplemental intervention to try and mimic its effects. He is also very intelligent and makes some good points. I learned from his post that unlike CR resveratrol does not modulate IGF-1, but found that folic acid does. SO combining the two should be beneficial.

There was a life-span study in nematodes that showed both CR and resveratrol extended lifespan, but the two together did not have an additive effect. Also organisms without the SIRT1 gene were not life extended by either modality. Evidence is lacking in organisms longer-lived than rodents for CR or resveratrol, though there are some preliminary results for monkeys. Some people maintain CR won't be effective in humans for life extension for that matter.

I feel that non-CR interventions will come in two stages: too soon to know if they work, and too late to do me any good. That's why I experiment instead of waiting for proof.