nicholson

Hi folks: For those interested in the GlyNAC story, the following quotation from PMID: 35975308 - Kumar P. - may be of interest: Near the end, under the heading: "(c) GlyNAC is not the same as NAC-alone or glutathione-alone": "Although NAC and glutathione have antioxidant properties, the effect of their supplementation on age-associated defects are limited. We compared the effects of NAC-alone versus GlyNAC on cardiovascular function in old mice and found that only GlyNAC improved cardiac function and inflammation (leukocyte infiltration), and this was not achieved by NAC-alone. Human clinical trials supplementing NAC-alone did not find any improvement in RBC-glutathione concentations, oxidative stress, or inflammation (as TNFalpha), GlyNAC supplementation improved/corrected these outcomes in this RCT. .......................... " So, assuming this is correct, then supplementing NAC+Glycine together is far superior to either on their own, and even, it seems, to the supplementation of glutathione. The logic behind this counter-intuitive conclusion could possibly be that, since glutathione is created inside cells, when glutathione is supplemented it either isn't absorbed in the gut or, if it is absorbed, it is unable to gain access to cells. But the results of this study indicate that NAC and glycine apparently are both absorbed in the gut and are able to access cells, and having done so are able to produce glutathione there when needed. Rodney.

Incidentally, when I mentioned "rejuvenation" in a post above, regarding a very old domestic cat, I probably ought to explain in more detail. I have been clipping this cat's claws for 19 years. As a kitten they were pure white, very slim and razor sharp. Over the years they have gradually become 'fat', much longer, almost black and blunt. After supplementing 50 mg/kg of body weight/day of both glycine and N-acetylcysteine, within two weeks slim, pure white and razor sharp claws have appeared, protruding from the tips of the existing blunt claws. It could only have been caused by the supplementation. However, there is no improvement in this very old cat's serious mobility issues. My conclusion is that the cat has been deficient these nutrients - and the implied glutathione deficiency - for many years. Yet she has been fed cat foods that contain glycine and cysteine. And at an age of 19.5 she has lived about 35% longer than the typical life expectancy of this breed of cat. In six months I will know if supplementation in an equivalent amount affects my biomarkers. Rodney.

Well that was interesting. I emailed both Ownyourlabs and Life Extension. Ownyourlabs has yet to respond. Life Extension could hardly have been more helpful. It appears I will soon have a requisition for seven tests at a price perhaps one-third lower than going to Labcorp directly. But the tests I need are not in Life Extension's 'Ondemand catalog'. So I had to order through their main web page. The suggestions are much appreciated. If the results I get seem to be of general interest I will post about them when I get them. Thanks to Brian and Todd. Rodney.

Thanks Todd. Labcorp told me they must have a requisition from an authorized US source, and their 'On demand' service did not list the tests I am hoping to get. Ownyourlabs has not responded yet. Another possibilty is that perhaps next time I am in Montana I will stop unannounced at a clinic or two and see if one will provide me with the requisition. OTOH, I would prefer not to delay too long. Thanks Brian. I will contact Life Extension. Rodney.

Thanks, Todd, so much for this information. Very helpful. I have contacted Ownyourlabs.com and am awaiting a reply. But I see that of the seven tests I would like to have done (all but one of them selected from the tests in the GlyNAC paper, PMID: 35975308 - Kumar P.) three of them are not on the Ownyourlabs test list, despite being listed by Labcorp. The four tests that are on their list are hsCRP, insulin, Interleukin-6 and TNFalpha. The three that aren't are RBC glutathione, Interleukin-10 and usPSA. The last-mentioned being particularly important for me. I note that in the Kumar paper, the dosage that got the difficult-to-believe huge improvements in so many biomarkers was 100mg/Kg/d for each of Glycine and NAC. For my body weight that comes out at about 7g of each per day. Which seems huge since my NAC supply comes in capsules of just 660mg! But it often seems to be the case in nutrition that for many nutrients the amount needed for plenty-adequacy is tiny. So perhaps 4g/day is sufficient. And I find it difficult to believe that simple amino acids - of the kind found in many foods - are likely to be harmful. Which leads to the conclusion that the only reason the Kumar paper created such apparent benefits is that, with advancing age, the human digestive tract is no longer able to extract these two nutrients from food. But is able to asbsorb them, apparently. If I succeed in getting these tests done, I will post again whether or not the test results have changed after six months of supplementation.

Hi folks: I haven't posted here for a long time. I have been distracted, among other things by a case of the (almost) inevitable prostate cancer, the eventual outcome of which remains to be determined. (I never had any of the listed risk factors for it!) But the purpose of this note is to ask if anyone has advice about how to get a requisition from a US doctor for some rather obscure tests. I live in Canada. In Canada it is doubtful the lab that does the tests here has even heard of them. Let alone be able to administer them. The head office of the lab that does all the tests here, has never heard of the 'ultrasensitive PSA' test for example, and that one isn't even especially 'obscure'. And it is illegal here even to pay for tests you would like to have done, so, given the state the system is in, it will certainly not foot the bill for $700 of tests they have never heard of : ^ ((( Impressed (perhaps I shouldn't be?) by the most recent GlyNac paper, I was wondering if - at age 80 - I should start supplementing GlyNAC. If so it might make sense to get half a dozen relevant tests done at Labcorp, and do it again in six months to see if supplementation makes a difference. I have approached an MD in Montana who I briefly consulted with a few years ago. But she has not returned phone calls since I told her what I wanted. Any thoughts about how to get a requisition for five tests shown to be available on Labcorp's website? Or would all I would need to do is go in to a GP and ask? Labcorp REQUIRES a requisiton from an authorized US prescriber. All the best to everyone, and thanks for any responses, Rodney Nicholson. REGARDING GlyNAC: Of course, I will also be happy to listen to reasons why I should NOT start supplementing GlyNAC. But the sheer huge size of the improvements claimed, for so many seemingly-important biomarkers, makes it look like an easy decison. I have a 115-year old (human-equivalent) domestic cat here that I started supplementing GlyNAC a few weeks ago. And it is clearly exhibiting one small example of rejuvenation, and no evidence of negative effects. But the cat is obviously very old with serious mobility issues, so I am not expecting a miracle.

Please, Dean, READ what I post. This is not the first occasion - there have now been several - that have caused me to wonder whether your first language may be greek. It seems pretty clear to me what I said. I SAID: "so they too would have been teenagers, or close to that, at the time of the same famine. I suspect ...... ". All very clear, to me, that I was *suggesting* a *possible* explanation for Calment's out of the ballpark longevity. Not, obviously, making any kind of categorical statement about it. And I don't CARE what age her parents lived to because, AS I HAD SAID - and as you would have seen if you had bothered to read what I SAID and not what you had imagined I might have said - the swedish study had found that it was not THE CHILDREN of teenagers experiencing famine that lived to the greatest ages, but the GRANDCHILDREN. Are you able to understand the above? Kindly argue with things I actually say. Otherwise it is all a waste of time. Mine as well as yours. Rodney

There was a study done in Sweden (which apparently has astonishingly good records going back a long way) a few years ago which noticed that the swedes who had lived a REALLY long time were those those grandparents had been teenagers during major famines. This is a little surprising, but perhaps not completely implausible if you think about it carefully. This made me think about one of my grandmothers and her two sisters. She lived to 99.x and both her sisters lived to be over 100. I had previously thought it must indicate strong genetic heritage. But when I ran the numbers I realized that their grandparents would have been teenagers at the time of the great irish potato famine. Jeanne Calment had been born in 1875. Her grandparents had probably been born around 1825, so they too would have been teenagers, or close to that, at the time of the same famine. I suspect this may account for a sizeable portion of Calment's great longevity. And since it seems likely that famines will occur less frequently in the future than they have in the past, maybe we will never see anyone live beyond 123. Unless of course they are on CRON, and exercise only once or twice a week ;; ^ ))) Rodney.

Hi Dean: "Whenever I see someone use the word "surely"........... " Just to be clear, when I use the term "surely" I mean it to be interpreted as meaning: "It seems highly probable to me that ..... ". There are seven keystrokes in "surely " and 36 in the alternative. So "surely" does seem rather more efficient. The Oxford Dictionary's explanation of it: "Used to emphasize the speaker’s firm belief that what they are saying is true and often their surprise that there is any doubt of this" contains over 100 characters. I had thought that that was the meaning others attached to the word also? But perhaps not? Rodney.

"But how do we to relax and enjoy when we know that no path we choose matters?" Don't worry, be happy, Sthira. Assuming you can find a way to be. Rodney.

"Yet the feverish "pursuit of happiness" seems to cause more misery to the pursuers than if they would just relax and enjoy life." Exactly. Hence, the Dalai Lama's: " ........ the much more difficult question is: How does one obtain it?" If you wanted to seek it out - via Google for example - you can find him elaborating on this question. But I seem to have found it without the Dalai Lama's assistance. Don't ask me how, but I (a one-mouse experiment) am fairly sure it has a lot to do with my mother's conduct when I was a fetus. Rodney.

There is the story - not apocryphal I believe - of a woman who for decades had wanted to get an audience with the Dalai Lama, and finally did - a year or two ago. She felt, she said to him, this great need to understand the purpose of life. It is said his reply was: "Ahhh. That one is easy. Happiness is the purpose of life. But the much more difficult question is: How does one obtain it?" More will be found here: http://www.dalailama.com/messages/compassion, and plenty of other similar references will turn up in Google. Rodney.

Hi Dean: Regarding your: =========== As we've discussed in this thread, there are several confounders that are likely to make simply "being thin" very different from "practicing CR". Three of them with obvious health/longevity downsides are: Smokers are thinner than non-smokers People with latent chronic illnesses are thinner than healthy people Naturally thin people often eat crappy diets =============== I think you might consider adding the following to your above list: People who are 'effortlessly slim' (the "effortlessly" is important) must suffer from one of the following two phenomena: A) They have a 'poor appetite' which, it is intuitively obvious to me, is bad news of some sort. Surely, thoroughly healthy people would be expected to have a 'very healthy appetite' would they not? Or ...... B) They have a very robust appetite, eat plenty, but are still slim. Surely this must imply intestinal absorption problems? And if they are not absorbing all the calories in transit, what other very important nutrients is their digestive tract also not absorbing? I have observed previously that I have been quite struck by how many of my contemporaries who were unusually slim in their late teens and early 20s died before the rest of us. And the same is true of the Wisconsin CR monkeys, so I am not imagining this. Rodney. .........

Regarding zinc, bear in mind to be cautious about excessive supplementation: The Oregon State University page on this is very comprehensive. (They have greatly expanded it from the last time I saw it, and it was pretty thorough before!.) Here is a quote from it: "Adverse effects The major consequence of long-term consumption of excessive zinc is copper deficiency. Total zinc intakes of 60 mg/day (50 mg supplemental and 10 mg dietary zinc) have been found to result in signs of copper deficiency. Copper deficiency has also been reported following chronic use of excessive amounts of zinc-containing denture creams (>2 tubes per week containing 17-34 mg/g of zinc; 99). In order to prevent copper deficiency, the US Food and Nutrition Board set the tolerable upper intake level (UL) for adults at 40 mg/day, including dietary and supplemental zinc." In the light of this, note that most zinc supplement pills I have seen contain 50mg of zinc. So if you take one daily, that pill alone provides more than the daily upper limit on top of which at least some more will be being provided by food. But based on my experience, fwiw, anyone eating zero or only small amounts of animal products will certainly be appreciably deficient zinc. So supplementation, imo, is essential for those on diets with minimal animal products. But for me, one 50mg pill per WEEK brings my intake right up to the RDA. Another piece of evidence suggesting modest zinc supplementation may be vitally important, was a study of the Cu/Zn blood ratio in the elderly. It found an absolutely extraordinary seven times higher mortality among those in the highest tertile of the ratio than those in the lowest tertile, over a followup period of a mere four years. Presumably it would have been even greater if they had compared quintiles? Apparently, there is not much one can do to shift one's blood copper level. So it may be possible to lower this ratio by supplementation with an appropriate amount of zinc. It appears that a ratio of Cu/Zn of 1.0 is excellent, while 2.0 would be in advise-the-funeral-home territory. Mine was 1.25, certainly in the lowest tertile, but it would be nice if it were a little lower. I have found it difficult to get doctors to order this test because they don't have anything to *prescribe* based on the result of it. But you can tell the doctor, of course, that you plan to supplement zinc if the ratio isn't where you want it to be. In order to get my blood tested I took the full text of the paper with me - this has been posted about here previously - and when I met resistance to the idea of doing ANY tests, I brought it out and started lecturing this clueless twit of an excuse of a doctor about the details of it. She snatched the paper out of my hand and ran out the door. She didn't come back for 20 minutes - I timed it. When she came back she ordered the test without further discussion. I have since been irregularly supplementing 50 mg per week so I hope my number may now be closer to 1.0 than before. Rodney. ========== "The unverified conventional wisdom is almost invariably mistaken."

Thanks Casey for the recipe suggestions! I see you use besan. At the link below you will find my 'standard white sauce' recipe using besan and onion powder in place of white flour and butter. It produces an excellent texture, imo. Of course, flavorings should be added appropriate to the food it accompanies. https://www.crsociety.org/topic/11193-base-ingredients-for-sauces/ Rodney. ======= "The unverified conventional wisdom is almost invariably mistaken."