NIA's ITP: Yet More Supplement Failure...
Michael 27 Mar 2012
This is from the NIA's Interventions Testing Program (ITP), their large, multicenter, gold-standard lifespan study to test out potential anti-aging drugs and supplements in normal, healthy, nonobese, non-toxin-fed, genetically-intact, well-cared-for mice; it's the same program that revealed the breakthru' results with rapamycin, but that has more quietly flunked out many other agents in the process.
Add more to the flunk list. In previous studies, they've started the animals off in early adulthood (12 mo); here, they've started them at 4 mo, when they're fully reproductively adult but still growing and developing in part because an agent that *slows down* aging should, ceteris paributs, have a more dramatic effect when started earlier in life.
"
The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. ... We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with ... green tea extract (GTE), curcumin, oxaloacetic acid ["Benagene"], medium-chain triglyceride oil, and resveratrol ... We reported *previously* that adding RES[veratrol] to the diet starting at 12 months of age did not affect life span (11). However, it was hypothesized that RES, like caloric restriction, might have its greatest effect when started earlier in life (14). Therefore, testing was repeated starting the test diet at 4 months of age. ...
On the assumption that each mouse weighs 30 g and consumes 5 g food/day, the estimated daily doses of these agents would be: RES 50; curcumin 333; GTE 333; MCTO 10,000; and OAA 367 mg/kg body weight/day. ...
*None* of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of *midlife* deaths ["ie, roughly 600–800 days of age" -- actually young-adult] in females only."
It's worth noting that GTE-fed females also weighed significantly less than controls, suggesting some potential for crypto-CR; ther was a NS but apparent lower weight in GTE-fed males, too (Fig 1). Annoyingly, they seem not to have actually weighed the animals' food intake.
Reference
1. Randy Strong, Richard A. Miller, Clinton M. Astle, Joseph A. Baur, Rafael de Cabo, Elizabeth Fernandez, Wen Guo, Martin Javors, James L. Kirkland, James F. Nelson, David A. Sinclair, Bruce Teter, David Williams, Nurulain Zaveri, Nancy L. Nadon, and David E. Harrison.
Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice
J Gerontol A Biol Sci Med Sci first published online March 26, 2012
DOI: 10.1093/gerona/gls070
Forthcoming PMID: 22451473
Mind 27 Mar 2012
Michael 27 Mar 2012
Any result regarding healthspan?
Yes, although for reasons that escape me, only on GTE:
We also examined the effect of GTE on locomotor activity in 18-month-old mice to determine whether it improved this measure of health span. Pooling data across sites, there was no significant difference in locomotor activity between control and GTE-treated mice (control: 45920 ± 1484; GTE: 46137 ± 1441; mean ± standard error of the mean [SEM]) ... [nor] at any one site (TJL: control: 39420 ± 1744; GTE: 43133 ± 1812. UM: control: 55198 ± 3432; GTE: 52344 ± 3003. UT: control: 44193 ± 1785; GTE: 43261 ± 2086).
What is the consensus on Green Tea? Is not there relatively good human data (population studies) that supports green tea consumption? Not GTE, but the real stuff.
The evidence on green tea is actually surprisingly mixed. I think we can confidently say that it's likely protective against CVD; I think the evidence also supports it being protective against some cancers, but only at a higher dose than most studies can granularly evaluate (certainly >5 x 150 mL cup, and more likely at 10 x 150 mL cup). High doses have also been reported to reduce total mortality in three prospective Japanese studies (but note that this seems to have been (almost?) entirely due to CVD in 16968850, and NOT to cancer), which I again find convincing, tho' the study count is limited and it's confined to a Japanese population, where the risk mix is of course different from what it is in North Americans (lifestyle-wise, and genetically, for those of Euro descent).
The more consistently favorable findings in Japan vs China may relate both dose (more Japanese drinking high volumes) and possibly the quality of the tea itself, tho' it could also be that there are still too many Chinese dying of things against which green tea is not likely to protect (especially in the time range in which such studies have been performed -- necessarily, before China's recent boom really got going).
I favor Japanese sencha to be 'sure.'
Edited by Michael, 27 March 2012 - 09:09 PM.
Luminosity 28 Mar 2012
rwac 28 Mar 2012
The major country with the highest longevity is Japan which also consumes large amounts of green tea.
In the last couple of years, they've found 'missing centenarians' who may have died years ago, but are kept alive on paper so that their families continue to get their pensions. I really wonder how bad the abuse is, and whether it actually affects Japan's longevity statistics.
Edited by rwac, 28 March 2012 - 04:01 AM.
Estrogen 28 Mar 2012
Almost every study comparing eastern vs western way of life favores the east [and bare in mind that japanese aren't less developed than western countries, which is often a factor in such studies] .
Anti-obesity, anti-diabetic and anti-cancer actions of EGCG are very well documented in countless studies [both in vitro and in vivo] from all over the world, so I feel preety confident taking my Fish oil, Vitamin D and EGCG extract daily.
Edited by Estrogen, 28 March 2012 - 09:03 AM.
niner 28 Mar 2012
While I can't go as far as saying humans are not rats, I'll go on record as saying rats are not human.
mikeinnaples 28 Mar 2012
gamesguru 28 Mar 2012
Japan, particularly Okinawa, has a high life span if this guy has his stats right: http://www.ted.com/t..._to_be_100.html.
Attributing their longevity solely, or even primarily, to green tea is simply ignorant. I think it has more to do with caloric restriction, phytonutrients (in a variety of fresh veggies) usually organic (better diet overall), friendship (Americans hate each other openly, Europeans only secretly...but these Japs are the true hippies), kinship (better sense of community), and exercise. Other factors play a role, but let's not use their consumption of green tea as an excuse to justify our bias. Logically speaking, their correlation between lifespan and tea consumption is a horrible data point. It's something I would expect out of a supplement company, not an inquirer. Plus, it's not even clear what kind of tea they drink, and I guarantee you they aren't consistent. I like how other members distinguished between the extract and the real thing. As far as my knowledge goes, green tea has fluoride and other compounds which aren't good in huge doses, but the extract should isolate the "therapeutic" compounds, thus allowing to see just how "therapeutic" they actually are. I don't think EGCG and other catechins/polyphenols are good if abused, but like other antioxidants, the evidence is starting to show they are mildly helpful when used in moderation. There are other compounds that play a role, like theanine and caffeine.
Edited by dasheenster, 28 March 2012 - 02:53 PM.
albedo 30 Mar 2012
Just for my understanding, do you mean the Body Surface Area (BSA) methodology as reported in the attached document? The HED based on BSA would give about 3.8g of GTE for a 70kg human adult which I guess is still high.Michael's quoted text does report a little curve squaring with the GTE, so that's consistent with it being good for you. The thing that's weird is the estimated doses: 333mg/kg for GTE? 23 grams a day for an adult human? Even if you apply the rat to human interspecies scaling factor, it's still high. Can those little rat livers process that much?
While I can't go as far as saying humans are not rats, I'll go on record as saying rats are not human.
Attached Files
Snoopy 11 May 2012
Green tea is a core constituent in Protandim - I trust Jo's findings seeing as he was the one who discovered SOD and it's activators....
Green tea is a definite goer in my opinion....
SocietyOfMind 11 May 2012
Asians definitely live longer & suffer less often from various diseases [mostly diabetes, prostate cancer, breast cancer].
I wonder if height has been ruled out as a factor in longevity?
nittybitty 11 Jul 2012
"Researchers from the Linus Pauling Institute at Oregon State University (Corvallis, Ore.) have tested white tea's ability to protect bacteria from DNA damage and found white tea to be a much more powerful antimutagen than green tea"
according to this article:
http://findarticles....2/ai_108051746/
Dorian Grey 11 Jul 2012
The Japanese smoke more than anyone else, and also live longer than about anyone else. The tobacco use keeps them from getting FAT.
They drink green tea (which blocks iron absorption), and eat fish (half the heme iron of red meat) instead of hamburgers.
Other than that, stress, pollution and most other factors are about equal, so let's drink real green tea, and enjoy a smoke with it! You can have my share of the fish-heads and rice... I'll donate blood a couple times a year to compensate for the hamburgers.
Edited by synesthesia, 11 July 2012 - 09:27 PM.
kismet 29 Jul 2012
niner 29 Jul 2012
gamesguru 30 Jul 2012
EVOO is also not something readily testable by science. Unless you controlled the relative levels of the various saturated and unsaturated fats, you couldn't say anything scientifically conclusive about a single study involving them, however large. Even if that were the case, you wouldn't be able to say which fatty acids accounted for what. It's much better to test individual fats. For example, test palmitic acid or oleic acid. Compare that to pure linoleic acid or alpha-linolenic acid (potentially harmful). Control all other variables and see which fatty acid confers the greatest increase in longevity. That's about as scientific as we know how to get.
I would also like to see C60 studied more, though we'd have to control its solution.
dear mrclock 30 Jul 2012
A very high quality study. Kudos for the quick discovery.
Japan, particularly Okinawa, has a high life span if this guy has his stats right: http://www.ted.com/t..._to_be_100.html.
Attributing their longevity solely, or even primarily, to green tea is simply ignorant. I think it has more to do with caloric restriction, phytonutrients (in a variety of fresh veggies) usually organic (better diet overall), friendship (Americans hate each other openly, Europeans only secretly...but these Japs are the true hippies), kinship (better sense of community), and exercise. Other factors play a role, but let's not use their consumption of green tea as an excuse to justify our bias. Logically speaking, their correlation between lifespan and tea consumption is a horrible data point. It's something I would expect out of a supplement company, not an inquirer. Plus, it's not even clear what kind of tea they drink, and I guarantee you they aren't consistent. I like how other members distinguished between the extract and the real thing. As far as my knowledge goes, green tea has fluoride and other compounds which aren't good in huge doses, but the extract should isolate the "therapeutic" compounds, thus allowing to see just how "therapeutic" they actually are. I don't think EGCG and other catechins/polyphenols are good if abused, but like other antioxidants, the evidence is starting to show they are mildly helpful when used in moderation. There are other compounds that play a role, like theanine and caffeine.
this guy +10
reading other people, no offense, but they sounded stupid :/
gamesguru 31 Jul 2012
Dr. Weil reports in his 2006 talk "Healthy Aging" (made into movie format) that a lot of the apparently impressive statistics of Okinawa are due to family members claiming birthdates of long-deceased relatives. It makes sense they would do this if money were to be involved, so thanks for adding your two cents.The major country with the highest longevity is Japan which also consumes large amounts of green tea.
In the last couple of years, they've found 'missing centenarians' who may have died years ago, but are kept alive on paper so that their families continue to get their pensions. I really wonder how bad the abuse is, and whether it actually affects Japan's longevity statistics.
Edited by dasheenster, 31 July 2012 - 01:49 AM.
Michael 09 Mar 2013
Dr. Weil reports in his 2006 talk "Healthy Aging" (made into movie format) that a lot of the apparently impressive statistics of Okinawa are due to family members claiming birthdates of long-deceased relatives. It makes sense they would do this if money were to be involved, so thanks for adding your two cents.In the last couple of years, they've found 'missing centenarians' who may have died years ago, but are kept alive on paper so that their families continue to get their pensions. I really wonder how bad the abuse is, and whether it actually affects Japan's longevity statistics.The major country with the highest longevity is Japan which also consumes large amounts of green tea.
Dr. Weil is wrong about this, as about so many other things. Pension fraud in Japan is a prominent issue, but whether it's so rampant as to affect the longevity statistics for the country as a whole is not known; in any case, it isn't driving the Okinawan centenarian phenomenon, which (unlike many other claims of longevity hotspots) has been rigorously documented for individual cases by cross-checking against independent records and tested for biological plausibility ("assessment of age heaping, maximum age at death, centenarian proportions, and male to female ratios").(1)
Reference
1: Willcox DC, Willcox BJ, He Q, Wang NC, Suzuki M. They really are that old: a validation study of centenarian prevalence in Okinawa. J Gerontol A Biol Sci Med Sci. 2008 Apr;63(4):338-49. PubMed PMID: 18426957.
Luminosity 11 Mar 2013
Japan, particularly Okinawa, has a high life span . . .
Attributing their longevity solely, or even primarily, to green tea is simply ignorant. I think it has more to do with caloric restriction, phytonutrients (in a variety of fresh veggies) -- dasheenster
There are many Japanese nationals where I live, as well as people of Japanese ancestry. Ditto for Okinawans. They don't actually eat that many fresh veggies. Their longevity has a number of causes, but green tea is one of them. -- Luminosity
usually organic (better diet overall), friendship (Americans hate each other openly, Europeans only secretly...but these Japs are the true hippies),-- dasheenster
Although they have a better sense of community and family, the Japanese are as far from hippies as anyone on earth. -- Luminosity
kinship (better sense of community), and exercise. Other factors play a role, but let's not use their consumption of green tea as an excuse to justify our bias. Logically speaking, their correlation between lifespan and tea consumption is a horrible data point. It's something I would expect out of a supplement company, not an inquirer. Plus, it's not even clear what kind of tea they drink, -- dasheenster
They drink a lot of green tea. It's not a mystery. -- Luminosity
and I guarantee you they aren't consistent.
Not sure what this is based on. If anyone on earth is consistent, it would be them. -- Luminosity
I like how other members distinguished between the extract and the real thing. As far as my knowledge goes, green tea has fluoride and other compounds which aren't good in huge doses, but the extract should isolate the "therapeutic" compounds, thus allowing to see just how "therapeutic" they actually are. I don't think EGCG and other catechins/polyphenols are good if abused, but like other antioxidants, the evidence is starting to show they are mildly helpful when used in moderation. There are other compounds that play a role, like theanine and caffeine. -- dasheenster
The whole is larger than the sum of it's parts. When we try to extract one thing from a natural product hoping that is the "active" ingredient, we are kidding ourselves. They all work together. -- Luminosity
Edited by Luminosity, 11 March 2013 - 03:04 AM.
gamesguru 14 Mar 2013
I don't know where you get the impression that hippies have the greatest sense of community compared with all other factions, but I'd like to just thank you for admitting that the Japanese, particularly the Okinawans, have a better sense of community, than much of Europe or North America.
When you say, "they drink a lot of green tea", I have to assume you've looked into the national statistics (and are not merely judging based on Japanese with whom you have personal acqauintence), which reveal a per capita consumption of tea leaves equal to three cups of tea per week per person? There are many who drink it like water, 8-10 cups per day. But they are balanced out by people who drink only water, or people who prefer coffee to tea. In fact, Japan consumes half the per capita tea leaves as Britain(1 kg yearly vs 1.9 kg yearly)! And you want to attribute their longevity to tea consumption? Your temperament appears to be statistically-unsound. My own temperament is perhaps equally unsound, but I think slightly less so. I think that a greater variety of foods, and a calmer, less stressful community life are the main reasons why Okinawans have a significantly higher life span (even after correcting for the lies they tell to the government for pensions).
My claim that they are inconsistent is based on the facts that many Japanese today drink tea less than one cup of tea per month, that many of them prefer black or oolong tea, that some pick up or drop the habit of tea drinking in the middle of life, and that there're 40,000 other variables that you can't control during their life which will interfere with the data collection.
I guess you're free to decide what causes their longevity, according to your temperament, because the uncontrolled variables make it impossible for science to tell us. It's a matter of temperament, not reason.
And lastly, there are some cases where botonical extracts are more effective or safer than the whole plant material. For example, raw ginkgo often contains too high a concentration ginkgolic acid, a toxin, in proportion with its active chemicals...which basically means you poison yourself before you medicate yourself. Whereas many who wish to use bacopa must use an extract, because they repeatedly suffer gastrointestinal distress when dosing the quantities of raw herb required to obtain the desired dose of bacosides (about 20 grams of powdered bacopa root daily! that's a lot to stomach!). It goes deeper than that, however.
The only reason why a plant would be superior to the extract of all its active chemicals is that the fiber, bulk materials, or trace chemicals play some crucial role, interacting with, and potentiating the action of the active chemicals. I find it very unlikely fiber will enhance the function of EGCG or catechins (especially since it's lacking in tea!). You're just painting a picture which is too complicated. Sure chemicals interact, but looking at cannabis, which I'm told contains over 80 cannabinoids, and 130 essential oils, terpenes, and other antioxidents, we saw the failures of dronabinol were soon triumphed by nabiximols. Dronabinol gave people headaches, made them upset, nauseas, and did little to relieve their symptoms. Adding CBD to THC, going from 1 chemical to 2, made a world of difference...people find nabiximols relaxing, not upsetting, and it finally brought that same relief of symptoms to those with epilepsy, muscle spasms, pain, and insomnia which the plant itself brings. I'm not saying those other 209 chemicals are completely insignificant, just practically; and I see more and more papers published showing that extracts have greater efficacy than the plant itself, despite the fact that the extract process cuts out hundreds of trace phytochemicals. Sorry, but I disagree with your wholistic philosophy; though I once shared a similar temperament, that processing foods is always bad, I now realize extracts can be used, supplementally, to squeeze more health benefits out of every hour and day.
Edited by dasheenster, 14 March 2013 - 03:51 PM.
mikeinnaples 14 Mar 2013
The whole is larger than the sum of it's parts. When we try to extract one thing from a natural product hoping that is the "active" ingredient, we are kidding ourselves. They all work together. -- Luminosity
This absolutely cannot be used as a blanket statement because it simply is not even remotely close to the truth.
Luminosity 15 Mar 2013
This absolutely cannot be used as a blanket statement because it simply is not even remotely close to the truth.
Yes it is.
Responding to dasheenster:
According to one study, Japanese and British vegetable consumption levels have remained stable over the past 45 years. However, the average Japanese person consumes vegetables with 2 out 3 meals, while the average British person consumes vegetables with only 1 out of 5 meals. Further, it shows the Japanese prefer raw cabbage, whereas the British prefer cooked. It does not, in the abstract, discuss quantities or per capita consumption, but these stats are refreshing, and I think sufficient evidence to cast doubt on your unsupported claim that "they don't actually eat that many fresh veggies". -- dasheenster
According to actual life, where I have been surrounded by Japanese people my whole life, they eat a small amount of pickled vegetables or perhaps little bit of seaweed, or a small amount of raw vegetables as part of some of their meals. By volume they don't actually eat that many vegetables on average. The average upscale or educated American eats more vegetables than the average Japanese person. The people of Japanese ancestry where I live who are not Japanese nationals eat fewer vegetables than that. They eat a lot of rice and animal protein, and a fair amount of grease and fried food. They drink a fair amount of sodas. That population was by and large descended from the rural poor in Japan over a hundred years ago and were brought here to work in agriculture. Okinawans here are roughly analogous. The amount of vegetables that Japanese nationals eat is probably stable for the last 45 years, it's just low. -- Luminosity
This isn't to say that eating vegetables won't help you live longer, I believe that it will. It just means that you can't use the Japanese to prove that. Their vaunted vegetable consumption has become something of an urban legend and taken on a life of it's own. It just isn't happening.
When you say, "they drink a lot of green tea", I have to assume you've looked into the national statistics (and are not merely judging based on Japanese with whom you have personal acqauintence), which reveal a per capita consumption of tea leaves equal to three cups of tea per week per person? There are many who drink it like water, 8-10 cups per day. But they are balanced out by people who drink only water, or people who prefer coffee to tea. In fact, Japan consumes half the per capita tea leaves as Britain(1 kg yearly vs 1.9 kg yearly)! And you want to attribute their longevity to tea consumption? Your temperament appears to be statistically-unsound. My own temperament is perhaps equally unsound, but I think slightly less so. I think that a greater variety of foods, and a calmer, less stressful community life are the main reasons why Okinawans have a significantly higher life span (even after correcting for the lies they tell to the government for pensions).
Personal insults do nothing to disguise the paucity of your arguments. Three cups of tea per week up to ten per day is enough tea to help you live longer. It would be mostly green tea, more than anything else. If you walk into a sushi bar or Japanese restaurant right now, if they have tea it would likely be green tea. If you walk into a Japanese grocery store where I live, over 90% of the tea will be green tea. The British drink black tea, some with milk and sugar. As for Okinawa, there are many reasons for longevity, probably including the ones you mentioned. No one says it is only this or that.
My claim that they are inconsistent is based on the facts that many Japanese today drink tea less than one cup of tea per month, that many of them prefer black or oolong tea, that some pick up or drop the habit of tea drinking in the middle of life, and that there're 40,000 other variables that you can't control during their life which will interfere with the data collection.
Like many traditional cultures, historic tea drinking habits may be changing, but as longevity statistics necessarily refer to older generations, we can still look to Japan for the effect of green tea on longevity. I'm not aware of another country that has traditionally drunk more green tea.
I guess you're free to decide what causes their longevity, according to your temperament, because the uncontrolled variables make it impossible for science to tell us. It's a matter of temperament, not reason.
You seem to have a hard time focusing. I've never said only one thing makes the Japanese live longer. In fact, I've said more than once that it isn't.
I didn't say that you could never use a plant extract, but you can never simply assume you have the "active ingredient" especially with a complex substance like tea. There is not just one "active ingredient" in tea. The whole plant is the medicine. Your argument portrays poor comprehension. It is also a strawman argument. You are going through life reducing things to the point of absurdity. There seems to be a lack of life experience.
The largest cultural group where I live and grew up is Japanese and that counts. Just because something is written up doesn't necessarily make it better than a lifetime of observation. Your own research papers contradict each other. Posing as unemotional, rational and somehow having more facts than another person doesn't make it so. There's nothing wrong with using a lifetime of direct observation to take conclusions from.
Edited by Luminosity, 15 March 2013 - 06:58 AM.
Kevnzworld 15 Mar 2013
Here is the chart from the study:
Table 1 Medium Survival for each Intervention pooled across sites for each gender.
Group Males Females
Control 786 (742-826) 866 (832- 891)
Curcumin 808 (744-838) 905 (836-933)
Green Tea 822 (769-880) 923 (887-939 )
Oxaloacetic acid 819 (756-857) 889 (859-937)
Resveratrol 813 (763-863) 907 (871-938)
One quote from the study.
" Similarly, it was reported that male C57BL/6NNia mice, fed TC the primary blood metabolite of curcumin, at a concentration of 2000 ppm in diet starting at 13 months, had an 11.7% greater mean life span as compared with mice fed the control diet, "
In the female mice group fed resveratrol, all of the mice lived longer than the medium survival of the controls.
In the female mice group fed GTE , all of the mice survived longer than the longest living control.
I thin that its important to consider that some of the beneficial actions attributed to these supplements may work on maladies that longer lived mammals suffer and die from, like cardiovascular disease and dementia. So one wouldn't expect to see the same longevity benefit in short lived mammals.
Yet given the table and data above....I would STILL rather be a supplemented mouse than a control mouse.
The full study....
http://resveratrolce...ngevitStudy.pdf
Edited by Kevnzworld, 15 March 2013 - 03:21 PM.
Methos000 15 Mar 2013
One of the lifespan tables from the ITP study:
Table 1 Medium Survival for each Intervention pooled across sites for each gender.
Group Males Females
Control 786 (742-826) 866 (832- 891)
Curcumin 808 (744-838) 905 (836-933)
Green Tea 822 (769-880) 923 (887-939 )
Oxaloacetic acid 819 (756-857) 889 (859-937)
Resveratrol 813 (763-863) 907 (871-938)
[MR SNIP] The full study....
http://resveratrolce...ngevitStudy.pdf
Edited by Michael, 16 March 2013 - 12:25 PM.