280 replies to this topic

[Darryl]

Spermine works too, in vitro. Tell your partners.

Chae, Yong-Byung, and Moon-Moo Kim. "Activation of p53 by spermine mediates induction of autophagy in HT1080 cells." International journal of biological macromolecules (2013).

This does raise the issue of whether regular induction of p53 by polyamines might increase irreversible senescence.

Edited by Darryl, 01 December 2013 - 06:30 PM.

[timar]

Here's the fatty acid profile:
http://www.essential...rm-analysis.htm

This is what I had in mind. No trace of any long chain omega-3 fatty acid. I would have been more than surprised, because if it did contain any, it would be unique in the higher plant kingdom and we all would know about it.

Spermine works too, in vitro. Tell your partners.

Fortunately(?), I don't have an in-vitro partner

This does raise the issue of whether regular induction of p53 by polyamines might increase irreversible senescence.

Interesting paper. Seems like it may be a good idea to combine polyamines with PI3K/Akt/mTOR inhibitory substances, so better have some berries with your wheatgerm cereal. Soy may be a good bet, because it contains high levels of both sperm(id)ine and inhibitory isoflavones.

Edited by timar, 01 December 2013 - 09:23 PM.

[DorianGrey]

Update: I have now ordered some Wheat Germ from Swansons.


Of course it could be vice versa and the oil is much lower per gram than e.g. the Bob's Red Mill wheat germ.

just read along another concern, "Wheat Germ Agglutinin", wheat germ should be loaded. Any opinion on that?

I just got my order from Swanson's including wheat germ. I think I won't need to buy this expensive Wheat Germ Oil for bringing up my polyamines, I tend to agree it's probably all contained in the protein fraction..

Regarding the Agglutinin issue I found existing threads here on the forum, very interesting theory that this could cause autoimmune diseases like rheumatoid arthritis.
There's a study that shows that WGA doesn't normally pass into the blood stream. There exists a fermented version of wheat germ that is great for cancer remission and wouldn't have WGA. Therefore I will just take care that I ingest some kefir whenever I add wheat germ into my diet, that should do the trick and I started kefir (any fermented milk drink is probably fine) anyway.
I don't like the natural yogurt for its taste, that would do the fermenting job in the guts maybe even better. I don't think it is necessary for a healthy person to do the fermenting of wheat germ with sourdough cultures upfront. That is the process this Hungarian guy uses who markets "Avemar" FWGE http://en.wikipedia....at_germ_extract .


Sorry for the confusion with the long-chain fatty acids, my last post was written a bit in a rush. I meant octacosanol which is of course a very long-chain (C-28) alcohol. The omega-3 in wheat germ oil is mainly your common linolenic acid. Thanks also for the link to these other oils, good overview!

[timar]

Regarding the Agglutinin issue I found existing threads here on the forum, very interesting theory that this could cause autoimmune diseases like rheumatoid arthritis.
There's a study that shows that WGA doesn't normally pass into the blood stream. There exists a fermented version of wheat germ that is great for cancer remission and wouldn't have WGA. Therefore I will just take care that I ingest some kefir whenever I add wheat germ into my diet, that should do the trick and I started kefir (any fermented milk drink is probably fine) anyway.
I don't like the natural yogurt for its taste, that would do the fermenting job in the guts maybe even better. I don't think it is necessary for a healthy person to do the fermenting of wheat germ with sourdough cultures upfront. That is the process this Hungarian guy uses who markets "Avemar" FWGE http://en.wikipedia....at_germ_extract .

Assumed that wheat germ agglutinin is of any concern for healthy people (which I doubt - sounds suspiciously like another variation of the well-worn Paleo theme of the "evil grain"), I doubt that it would make any difference to ingest it with yogurt or kefir. Even if the yogurt contains probiotic cultures which survive the stomach acid, they become active only in the large intestine where they join with the 99.99% of the existing bacterial population. If the agglutinins would be absorbed in the small intestine, it couldn't be fermented. If it would be absorbed in the large intestine, the additional "drop in the ocean" of intestinal bacteria could hardly make any difference.

Edited by timar, 06 December 2013 - 06:43 PM.

[smithx]

Where does the spermidine in semen come from?

In other words, would supplementing some quantity of spermidine be equivalent for a male to not ejaculating for some period of time, or is there no relation between the spermidine in semen and the spermidine in the rest of the body which could be useful for longevity?

If not ejaculating could increase spermidine levels in a man, then the Taoists who recommended not ejaculating as a means towards longevity could have been on the right track.

But if spermidine production takes place in the prostate and is broken down and not distributed to the rest of the body if it is not ejaculated that's another story.

Are there any data?

[hav]

Fwiw, I was just reading up on speridine metabolism and it seems that all the enzymes needed are found within cells. Not sure if it can normally find its way out and about, but aging reduces internal production. Suggesting that conservation might have an effect in the middle-ages between over- and under-supply.

I was curious about a tangential possibility. Creating liposomes to deliver spermidine or its metabolites. I was thinking spermidine might fair better than l-arginine or l-cysteine with the ultrasound process. The goal would be to induce nitric oxide dilation effects on lymphatic vessels and nodes, similar to those normally observed on blood vessels. Looks like if it could be delivered, normal metabolism would happen. Any thoughts?

Howard

[Darryl]

Suggesting that conservation might have an effect in the middle-ages between over- and under-supply.

Group Capt. Lionel Mandrake: Uh, Jack, Jack, listen... tell me, tell me, Jack. When did you first... become... well, develop this theory?
General Jack D. Ripper: [somewhat embarassed] Well, I, uh... I... I... first became aware of it, Mandrake, during the physical act of love.
Mandrake: Hmm.
Ripper: Yes, a uh, a profound sense of fatigue... a feeling of emptiness followed. Luckily I... I was able to interpret these feelings correctly. Loss of essence.
Mandrake: Hmm.
Ripper: I can assure you it has not recurred, Mandrake. Women uh... women sense my power and they seek the life essence. I, uh... I do not avoid women, Mandrake.
Mandrake: No.
Ripper: But I... I do deny them my essence.

Ripper was a character clearly concerned with his polyamine balance.

Edited by Darryl, 08 December 2013 - 07:55 PM.

[Darryl]

Useful review:

Minois, Nadège. "Molecular Basis of the ‘Anti-Aging' Effect of Spermidine and Other Natural Polyamines-A Mini-Review." Gerontology (2014).

[VERITAS INCORRUPTUS]

Any users see an improvement in mood, along with any other notable effects?

[mikey]

 

guys where do you get your infos from ? i checked this "http://www.ncbi.nlm....es/PMC3022763/" and highest content of spermidine is found in aged cheese. in the table on the url it shows 200mg for cheese ! i cant see anything else that high.
meat also has good amount. but check this table to see what i mean "http://www.ncbi.nlm..../figure/F0001/"
in there you can clearly see aged cheddar cheese blows everything apart in content. so what is this talk about gulping canned corn about ?? i assume you guys are vegetarians and are scared of cheese :P

Maybe cheese is the true French paradox rather than wine.

 

 

It seems likely that the true French Paradox is the grass-fed pasture raised dairy fats, which contain high amounts of vitamin K2 (MK-7), which fuels matrix Gla protein to direct calcium away from soft tissues, such as arteries while it also fuels osteocalcin to pull calcium into bones and teeth. 

 

And now we find another potential longevity ingredient in these cheeses with their high spermidine content.

 

It appears that resveratrol (red wine) might be a minor component in the French Paradox, rather than the major ingredient.

[scottrobb1982]

I like soybeans alot, but they contain goitrogens. Sweetcorn is what I trailed with just lately. Taking note of overdoing it on the spermidine....documented all my work on youtube: youmukranda (scottrobb0

[resveratrol_guy]

With regards to longterm spermidine supplementation:

 

For years, I've been trying to determine an explanation for my mother's prodigious memory. At 67, she routinely calls me with updates on some minor topic we discussed previously, with some relevant minutia which she found on the Web. (She's definitely obsessive-compulsive.) I can pull a decades-old photo out of the album, and she almost always remembers the situation. Over the years, she has taken little more than a multivitamin per day in order to ensure sufficient nutrition. And she now takes (only) 50mg of resveratrol per day, and maybe more vitamins D and B. But what's remarkable is that, otherwise, her diet is of the standard American variety. I can hardly eat at her home, save for some frozen veggies tucked in the back of her freezer and a few nuts. Her shelves are stocked with industrial food: packaged pastries, crackers, refined grain cereals, milk, processed meat products, candy, high-sugar yoghurt, corn chips, honey, jam, ice cream, and other junk; her "health" food is raisins. Her saving grace is that she consumes a minimum of calories, which no doubt accounts of some of the effect. But she looks rather catabolic, and shows signs of vasculitis and edema in her lower legs. Her fasting glucose was 91 several years ago, and is almost surely higher now. Yet, her memory is amazing.

While I've been forced to accept that it's her life and she won't change her habits, I haven't stopped wondering how this can be so. I can assure you that her memory is better than mine, which Lumosity currently rates as 96th percentile in my age group (probably an overestimate, but it's good nonetheless).

So when I stumbled upon this thread, I asked her about her consumption of various foods rich in spermidine (which I assume is equivalent to the "spermidin" mentioned in the fruit fly study). It turns out, as I recall from my youth, that she has been consuming "an eighth of a cup" of wheatgerm per day for the last 30 years or so, and likes to eat cheese on regular basis, particularly havardi. Corn chips are her favorite food, and her family had corn-on-the-cob on a regular basis. She is allergic to red wine and avoids the stuff, so this can't be explained by lifelong resveratrol ingestion.

 

I wouldn't be all that phased by any of this, save for the chasm of contradiction between her diet and memory performance. If nothing else, suffice to say that after all this spermidine consumption, she has never had any major illness (apart from flus and the like).

Her mother was French (if it matters to the French paradox) and neither of her parents developed dementia of any obvious form, which may have helped as well. Maybe this is all coincidence, but I've been trying to crack this for years, and the spermidine connection is the best thing I've found, for one thing, because it explains how she's constantly "taking out the garbage". I don't think good genes and moderate CR are much of a match vs. 67 years of junk food.

 

Edited by resveratrol_guy, 13 October 2014 - 05:12 PM.

[resveratrol_guy]

Sorry, I have to get this off my chest. If there is any explanation for this very typical day with my mother, apart from longterm spermidine consumption, let me know because whatever it is, I want to take it.

 

So I visited my dear mother today, who is almost exactly like Dilbert's mother. The first thing she mentioned after I sat down was that she had a step stool for me, as I had requested a week ago and had since forgotten. But it wasn't quite appropriate for my needs, so she remembered the locations of 3 other step stools in the house, and showed each of them to me, commenting on how one of them lacked sufficient friction and might be unsafe. Then she reminded me on a couple separate occasions to adjust my car tire pressure with her bike pump (she maintains her tire pressure herself), in between times helping me debug her document scanner problem. On the way out the door, she reminded me to pick up some papers that I had promised to collect, but had since forgotten. Then while filling my tires, she chatted to me about her car mechanic's anomalous discoveries regarding a misoriented air filter on some intake manifold under her hood.

 

Look, Lumosity has decided as of yesterday that my memory function is in the top 3% of my age group, but I can't keep up with my mother! It's embarrassing, already! And yeah, maybe Lumosity is full of it. So in my desperation, I asked if she had some chocolate so I could at least show her that I could remember something important, sooner than she thought of it herself. She said, "Sure, it's in the middle cabinet above the counter." I had a look, and found Reese's peanut butter cups, Mounds, and some other crap milk chocolate candy bar. No dark chocolate to be found, let alone anything organic or fair-trade. She said she still eats this stuff and has the audacity to call it "chocolate".

 

I then told her that I wanted her to see my previous post here on the forum. So I spent the next half hour trying to figure out what was wrong with her internet connection. I thought it was a browser issue, but she traced it to something with the DSL itself, and directed me to use her alternative connection tied to a different ISP. (This, after spending most of yesterday explaining to my wife how to drive through a city using Google Street View starting with an emailed link. I don't know how to explain that to anyone. You just click the yellow man, and it puts up street photos and stuff.)

 

Anyhow, I managed to bring up the post, which she said was entirely accurate, except for the corn chips, which she had recently given up on account of stomach upset. At last, one small victory!

 

Edited by resveratrol_guy, 15 November 2014 - 05:57 AM.

[ironfistx]

Since you guys brought up wheat germ, are there any other benefits of it as I saw some at the store the other day and wasn't sure if it was good or not and it was like just minimal slection of containers in that place.

[resveratrol_guy]

ironfistx, as you seem to realize, wheat germ is perhaps most accurately described as a fibrous antinutrient which sweeps a broad spectrum of trace elements and other water-soluable goodies out of the body before they can be absorped. (Public enemy number one is probably phytic acid or the lectin (sic) content, which masks leptin (sic) sensitivity according to a theory described here.)

 

But I suppose eating a small amount of it daily for the longterm would be OK apart from guaranteed halitosis, although it would probably alter one's gut flora for the worse. And definitely, stick to the non-toasted variety because we don't want to oxidize the spermidine! My mother has always eaten Kretshmer. I know because I used her red-top jars many times to catch lizards as a kid.

 

Better yet, find a healthier alternative source from this thread.

 

[DorianGrey]

ironfistx, as you seem to realize, wheat germ is perhaps most accurately described as a fibrous antinutrient which sweeps a broad spectrum of trace elements and other water-soluable goodies out of the body before they can be absorped. (Public enemy number one is probably phytic acid or the lectin (sic) content, which masks leptin (sic) sensitivity according to a theory described here.)

 

But I suppose eating a small amount of it daily for the longterm would be OK apart from guaranteed halitosis, although it would probably alter one's gut flora for the worse. And definitely, stick to the non-toasted variety because we don't want to oxidize the spermidine! My mother has always eaten Kretshmer. I know because I used her red-top jars many times to catch lizards as a kid.

 

Better yet, find a healthier alternative source from this thread.

Do you have any literature on that? I mix a few spoons of wheat germ with greek yogurt and in general drink a lot of tea. I guess the more liquid, the better you fight this "sponge" effect you were talking about, the stuff is quite dry. I keep it in a jar and every time you open the jar there is this smell, I think it's the spermidine. BTW, I have found a source at my local discounter, no need to order at Swanson's. Strangely, all the organic shops don't carry wheat germ.

[Darryl]

ironfistx, as you seem to realize, wheat germ is perhaps most accurately described as a fibrous antinutrient which

 

It boggles the mind that in an era where anyone can access 10⁸ abstracts with a few keystrokes, there are still those who take the pronouncements of a professor of Exercise Physiology on faith. Paleo shares in the modern nutritional consensus that we should all be eating less processed diets, and this is laudable. But Paleo's anti-grain, anti-legume, anti-phytate crusade is profoundly ignorant of modern evidence, and I fear, costly to human health.

 

First note whether these dietary restrictions of paleo pass the smell test. Consumption the best sources for phytate in the diet, whole grains and legumes, are consistently associated with lower heart disease, cancer, diabetes and other chronic disease incidence, and longer lifespans.

 

Then consider that mounting evidence demonstrates that some dietary minerals chelated by phytate, including iron, copper, manganese, are clearly harmful in excess.

 

Then peruse some reviews and abstracts:

 

Phytates

 

Harland, B. F., & Morris, E. R. (1995). Phytate: a good or a bad food component?. Nutrition Research, 15(5), 733-754.

Urbano, G., Lopez-Jurado, M., Aranda, P., Vidal-Valverde, C., Tenorio, E., & Porres, J. (2000). The role of phytic acid in legumes: antinutrient or beneficial function?. Journal of physiology and biochemistry, 56(3), 283-294.

Greiner, R., Konietzny, U., & Jany, K. D. (2006). Phytate-an undesirable constituent of plant-based foods?. Journal für Ernährungsmedizin, 8(3), 18-28.

Xu, Q., Kanthasamy, A. G., & Reddy, M. B. (2008). Neuroprotective effect of the natural iron chelator, phytic acid in a cell culture model of Parkinson's disease. Toxicology, 245(1), 101-108.

Schlemmer, U., Frølich, W., Prieto, R. M., & Grases, F. (2009). Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis. Molecular nutrition & food research,53(S2), S330-S375.

 

Phytates & cancer

 

Graf, E., & Eaton, J. W. (1985). Dietary suppression of colonic cancer fiber or phytate?. Cancer, 56(4), 717-718.

A. M. Shamsuddin, I. Vucenik, K. E. Cole. IP6: A novel anti-cancer agent. Life Sci. 1997 61(4):343 – 354.

Eggleton, P. (1998). Effect of IP6 on human neutrophil cytokine production and cell morphology. Anticancer research, 19(5A), 3711-3715.

Deliliers, G. L., Servida, F., Fracchiolla, N. S., Ricci, C., Borsotti, C., Colombo, G., & Soligo, D. (2002). Effect of inositol hexaphosphate (IP6) on human normal and leukaemic haematopoietic cells. British journal of haematology,117(3), 577-587.

Shamsuddin, A. M. (2002). Anti‐cancer function of phytic acid. International journal of food science & technology, 37(7), 769-782.

Vucenik, I., & Shamsuddin, A. M. (2003). Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic. The Journal of nutrition, 133(11), 3778S-3784S.

Vucenik, I., Passaniti, A., Vitolo, M. I., Tantivejkul, K., Eggleton, P., & Shamsuddin, A. M. (2004). Anti-angiogenic activity of inositol hexaphosphate (IP6). Carcinogenesis, 25(11), 2115-2123.

Shamsuddin, A. K., & Vucenik, I. (2005). IP6 & inositol in cancer prevention and therapy. Current Cancer Therapy Reviews, 1(3), 259-269.

Singh, R. P., & Agarwal, R. (2005). Prostate cancer and inositol hexaphosphate: efficacy and mechanisms. Anticancer research, 25(4), 2891-2903.

Vucenik, I., & Shamsuddin, A. M. (2006). Protection against cancer by dietary IP6 and inositol. Nutrition and cancer, 55(2), 109-125.

Bacić, I., Druzijanić, N., Karlo, R., Skifić, I., & Jagić, S. (2010). Efficacy of IP6+ inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study. J Exp Clin Cancer Res, 29(1), 1-5.

Kapral, M., Wawszczyk, J., Jurzak, M., Hollek, A., & Węglarz, L. (2012). The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells. International journal of colorectal disease, 27(11), 1419-1428.

 

Phytates & osteoporosis

 

López-González, A. A., Grases, F., Roca, P., Mari, B., Vicente-Herrero, M. T., & Costa-Bauzá, A. (2008). Phytate (myo-inositol hexaphosphate) and risk factors for osteoporosis. Journal of medicinal food, 11(4), 747-752.

Lopez-Gonzalez, A. A., Grases, F., Perello, J., Tur, F., Costa-Bauza, A., Monroy, N., ... & Vicente-Herrero, T. (2009). Phytate levels and bone parameters: a retrospective pilot clinical trial. Frontiers in bioscience (Elite edition), 2, 1093-1098.

del Mar Arriero, M., Ramis, J. M., Perello, J., & Monjo, M. (2012). Inositol hexakisphosphate inhibits osteoclastogenesis on RAW 264.7 cells and human primary osteoclasts. PloS one, 7(8), e43187.

López-González, Á. A., Grases, F., Monroy, N., Marí, B., Vicente-Herrero, M. T., Tur, F., & Perelló, J. (2013). Protective effect of myo-inositol hexaphosphate (phytate) on bone mass loss in postmenopausal women.European journal of nutrition, 52(2), 717-726.

 

Whole grains & legumes

 

Jonnalagadda, S. S., Harnack, L., Liu, R. H., McKeown, N., Seal, C., Liu, S., & Fahey, G. C. (2011). Putting the whole grain puzzle together: Health benefits associated with whole grains—summary of American Society for Nutrition 2010 Satellite Symposium. The Journal of nutrition, 141(5), 1011S-1022S.

Björck, I., Östman, E., Kristensen, M., Mateo Anson, N., Price, R. K., Haenen, G. R., ... & Riccardi, G. (2012). Cereal grains for nutrition and health benefits: Overview of results from in vitro, animal and human studies in the HEALTHGRAIN project. Trends in Food Science Smith, C. E., & Tucker, K. L. (2011). Health benefits of cereal fibre: a review of clinical trials. Nutrition research reviews, 24(01), 118-131.

Adil, G. (2012). Whole-grain cereal bioactive compounds and their health benefits: A review. Journal of Food Processing & Technology.

Darmadi-Blackberry, I., Wahlqvist, M. L., Kouris-Blazos, A., Steen, B., Lukito, W., Horie, Y., & Horie, K. (2004). Legumes: the most important dietary predictor of survival in older people of different ethnicities. Asia Pacific Journal of Clinical Nutrition, 13(2), 217-220.

Technology, 25(2), 87-100.Chang, W. C., Wahlqvist, M. L., Chang, H. Y., Hsu, C. C., Lee, M. S., Wang, W. S., & Hsiung, C. A. (2012). A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome. Public health nutrition, 15(04), 663-672.

Singh, J., & Basu, P. S. (2012). Non-nutritive bioactive compounds in pulses and their impact on human health: an overview. Food and Nutrition Sciences, 3, 1664.

Curran, J. (2012). The nutritional value and health benefits of pulses in relation to obesity, diabetes, heart disease and cancer. British Journal of Nutrition,108(S1), S1-S2.

Venn, B., Thies, F., & O'Neil, C. (2012). Whole Grains, Legumes, and Health.Journal of nutrition and metabolism, 2012.

 

... and you may just decide that the Cordain's crusade against whole grains and legumes (motivated largely by some ancient work on phytates) is woefully ill-informed, as are his many followers. Modern nutrition is no longer entirely about addressing nutrient deficiencies: nutrient excess plays an equally and even greater role these days, and that includes some minerals. Excluded here for brevity (and because it doesn't impinge upon the phytate story), but someday a member of the Ancestral Health Symposium will learn the words "microbiome" and "endotoxin" and start delving, and their head will explode from the cognitive dissonance with their cherished beliefs.

 

 

Edited by Darryl, 19 November 2014 - 06:22 PM.

[resveratrol_guy]

DorianGrey and Darryl, admittedly I didn't base my assumption that wheatgerm is an antinutrient on any specific literature. So it may well be the case that this stuff is beneficial in its net effect. I think it's helpful that Darryl provided all those links, although I wonder what other papers exist which show that it's junk like "regular" wheat. Nevertheless, my mother's experience would suggest that it's beneficial, as there is very little else in her nutritional history which is even vaguely suggestive of health benefits.

 

But I wonder whether it's associated with longer lifespans and other benefits because people who consume it tend to be calorically restricted vegans (or CRed junkatarians, like my mother). All I know is that we didn't evolve to eat this stuff (except under conditions of involuntary CR, i.e. starvation) because it takes way too much energy to gather relative to the calories that it provides. So common sense would say that it's at best pretty worthless. But nutritional science is nothing, if not counterintuitive. So others with the time to spare can read Darryl's linked papers, and those which contradict them, and enlighten us all on the matter.

 

[resveratrol_guy]

For the record, my mother and her sister and I had a chat about this thread over Thanksgiving dinner. When I explained to my mother that her caloric restriction was probably part of the answer, my aunt interjected that she actually ate less than my mother. (My aunt is more muscular than I am, and is in no way calorically restricted, although she has healthy BMI.) I asked my mother whether she consumed subnormal calories, and she said she didn't know (which is totally unsurprising, considering that she probably knows less about good nutrition than I know about the dark side of the moon). So I asked her if she ate until she felt she had eaten enough, or until she felt full. She affirmed the latter. Maybe I just presumed CR all these years because she's thin in a stereotypically French-woman way.

 

The conversation then turned to various restaurant experiences by way of example, with which I will not bore you, except to say that she remembered what she and my aunt had eaten on a trip to Rome several years ago; I can't even recall which year it was. But then she went on to relate a similar restaurant experience on a trip to France only several weeks ago, with details about what the two of them had eaten, and my aunt confirmed its veracity. Not that this is a scientific test. But I'm not sure I could tell you what I ate yesterday.

 

No doubt filled with the same sense of intergenerational rivalry that Dilbert experiences when he sits across the table from his mother, I sucked it up and had a plate of melted cheddar mixed with a pile of uncooked dry wheat germ in lieu of turkey. (Trust me, it's worth a try!) At least, I was pleased to see that she finally heeded my advice by avoiding the pumpkin pie crust, filling and Redi-whip notwithstanding. And she was proud to to tell me that, as a result of this thread, she had doubled her wheat germ intake.

 

So all this to say that I'm running out of sane hypothetical explanations for her memory performance. Maybe you guys are right: it's the wheat germ (and cheese), stupid! I really wish I'd had a clue so many years ago. Maybe this thread will benefit some of our younger lurkers. I hope so.

 

Edited by resveratrol_guy, 29 November 2014 - 03:12 AM.

[DorianGrey]

Wheat germ is a rich source of different forms of choline, as far as I know. That might explain part of what you observe. The high spermidine content is probably a contributing factor, thinking of mitchondrial membrane integrity (probably matters more than the cell membranes which are important, too). 

 

I use wheat germ (I think it is not toasted) in my Greek yogurt, but I do not overdo it, you need some liquid to get the solvents out, that stuff is like a sponge.

 

Choline might contribute to rejuvenation or at least slow down aging, alpha-GPC is one form that passes the BBB and is a nootropic I really want to try. It is popular among bodybuilders, these guys are the real biohackers, if you think about it, although probably not the live long and healthy type.

 

 

[resveratrol_guy]

I never thought I would use "wheat" and "nootropic" in the same sentence, but there's a large number of people in the Nootropics/Stacks section, including me, who chug down eggs or (expensive) alphaGPC in order to keep the choline flowing; you might suggest wheat germ as an experimental economical alternative. But to your larger point, yes, a steady supply of choline would create rather the opposite environment of an Alzheimer's brain.

 

[resveratrol_guy]

Just for the sake of public responsibility: I noticed that Kretshmer wheatgerm is supplemented with vitamin E (acetate form) and folic acid, which some studies have tied to premature mortality among seniors, and cancer, respectively. I don't have time to do the research, and this might be a nonissue, but I wouldn't feel right if I didn't mention this.

 

[Darryl]

Finally, a mechanism.

 

Pietrocola, F., Lachkar, S., Enot, D. P., Niso-Santano, M., Bravo-San Pedro, J. M., Sica, V., ... & Kroemer, G. (2014). Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death & Differentiation.

 

Several natural compounds found in health-related food items can inhibit acetyltransferases as they induce autophagy. Here we show that this applies to anacardic acid, curcumin, garcinol and spermidine, all of which reduce the acetylation level of cultured human cells as they induce signs of increased autophagic flux (such as the formation of green fluorescent protein-microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta and the depletion of sequestosome-1, p62/SQSTM1) coupled to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1). We performed a screen to identify the acetyltransferases whose depletion would activate autophagy and simultaneously inhibit mTORC1. The knockdown of only two acetyltransferases (among 43 candidates) had such effects: EP300 (E1A-binding protein p300), which is a lysine acetyltranferase, and NAA20 (N(α)-acetyltransferase 20, also known as NAT5), which catalyzes the N-terminal acetylation of methionine residues. Subsequent studies validated the capacity of a pharmacological EP300 inhibitor, C646, to induce autophagy in both normal and enucleated cells (cytoplasts), underscoring the capacity of EP300 to repress autophagy by cytoplasmic (non-nuclear) effects. Notably, anacardic acid, curcumin, garcinol and spermidine all inhibited the acetyltransferase activity of recombinant EP300 protein in vitro. Altogether, these results support the idea that EP300 acts as an endogenous repressor of autophagy and that potent autophagy inducers including spermidine de facto act as EP300 inhibitors.

 

 

[Logic]

Finally, a mechanism.
 
Pietrocola, F., Lachkar, S., Enot, D. P., Niso-Santano, M., Bravo-San Pedro, J. M., Sica, V., ... & Kroemer, G. (2014). Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death & Differentiation.

Several natural compounds found in health-related food items can inhibit acetyltransferases as they induce autophagy. Here we show that this applies to anacardic acid, curcumin, garcinol and spermidine, all of which reduce the acetylation level of cultured human cells as they induce signs of increased autophagic flux (such as the formation of green fluorescent protein-microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta and the depletion of sequestosome-1, p62/SQSTM1) coupled to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1). We performed a screen to identify the acetyltransferases whose depletion would activate autophagy and simultaneously inhibit mTORC1. The knockdown of only two acetyltransferases (among 43 candidates) had such effects: EP300 (E1A-binding protein p300), which is a lysine acetyltranferase, and NAA20 (N(α)-acetyltransferase 20, also known as NAT5), which catalyzes the N-terminal acetylation of methionine residues. Subsequent studies validated the capacity of a pharmacological EP300 inhibitor, C646, to induce autophagy in both normal and enucleated cells (cytoplasts), underscoring the capacity of EP300 to repress autophagy by cytoplasmic (non-nuclear) effects. Notably, anacardic acid, curcumin, garcinol and spermidine all inhibited the acetyltransferase activity of recombinant EP300 protein in vitro. Altogether, these results support the idea that EP300 acts as an endogenous repressor of autophagy and that potent autophagy inducers including spermidine de facto act as EP300 inhibitors.

Nice find.

Anacardic Acid looks interesting: Besides enhancing autophagy its anti everything at very low concentrations (read clinically effective) and causes blisters like poisen ivy when concentrated.
Vince G of Anti Aging Firewalls has an interesting write-up on it:
"...emerging evidence suggests that AA (anacardic acid) could be a potent target molecule with bactericide, fungicide, insecticide, anti-termite and molluscicide properties and as a therapeutic agent in the treatment of the most serious pathophysiological disorders like cancer, oxidative damage, inflammation and obesity. Furthermore, AA was found to be a common inhibitor of several clinically targeted enzymes such as NFκB kinase, histone acetyltransferase (HATs), lipoxygenase (LOX-1), xanthine oxidase, tyrosinase and ureases..."
http://www.anti-agin...lth-properties/

[RobbieG]

For those of us with vasectomies adding spermidine might make some sense:

 

" In 56 males, vasectomized 8 years previously..................A marked reduction was demonstrated in the ejaculatory contents of the polyamines, spermidine (366 vs 650 nmol, P less than 0.005) and spermine (5435 vs 11 804 nmol, P less than 0.05) but not their acknowledged precursor, putrescine, which is also of prostatic origin." 

 

http://www.ncbi.nlm..../pubmed/2621711

[Turnbuckle]

For those of us with vasectomies adding spermidine might make some sense:

 

" In 56 males, vasectomized 8 years previously..................A marked reduction was demonstrated in the ejaculatory contents of the polyamines, spermidine (366 vs 650 nmol, P less than 0.005) and spermine (5435 vs 11 804 nmol, P less than 0.05) but not their acknowledged precursor, putrescine, which is also of prostatic origin." 

 

http://www.ncbi.nlm..../pubmed/2621711

 

That's a good thing, right, not losing it? You're halfway to abstinence. 

[RobbieG]

You're right.  My first post and I fucked it up.  Well that didn't take long.  Thanks TB.    

[resveratrol_guy]

For the record, my mother and her sister and I had a chat about this thread over Thanksgiving dinner. When I explained to my mother that her caloric restriction was probably part of the answer, my aunt interjected that she actually ate less than my mother. (My aunt is more muscular than I am, and is in no way calorically restricted, although she has healthy BMI.) I asked my mother whether she consumed subnormal calories, and she said she didn't know (which is totally unsurprising, considering that she probably knows less about good nutrition than I know about the dark side of the moon). So I asked her if she ate until she felt she had eaten enough, or until she felt full. She affirmed the latter. Maybe I just presumed CR all these years because she's thin in a stereotypically French-woman way.

 

The conversation then turned to various restaurant experiences by way of example, with which I will not bore you, except to say that she remembered what she and my aunt had eaten on a trip to Rome several years ago; I can't even recall which year it was. But then she went on to relate a similar restaurant experience on a trip to France only several weeks ago, with details about what the two of them had eaten, and my aunt confirmed its veracity. Not that this is a scientific test. But I'm not sure I could tell you what I ate yesterday.

 

No doubt filled with the same sense of intergenerational rivalry that Dilbert experiences when he sits across the table from his mother, I sucked it up and had a plate of melted cheddar mixed with a pile of uncooked dry wheat germ in lieu of turkey. (Trust me, it's worth a try!) At least, I was pleased to see that she finally heeded my advice by avoiding the pumpkin pie crust, filling and Redi-whip notwithstanding. And she was proud to to tell me that, as a result of this thread, she had doubled her wheat germ intake.

 

So all this to say that I'm running out of sane hypothetical explanations for her memory performance. Maybe you guys are right: it's the wheat germ (and cheese), stupid! I really wish I'd had a clue so many years ago. Maybe this thread will benefit some of our younger lurkers. I hope so.

 

It turns out that mother has an HDL of 102 and LDL of 106, a highly unusual ratio in favor of HDL. No doubt this is supporting cerebrovascular function quite well. Sorry to muddy the waters, but I thought I should mention it.

[Tom Andre F. (ex shinobi)]

sorry to bump this topic. But i have important uestion here: do you guys think its necessary to use the combination spermidine + spermine ? Or spermidine alone would be fine ?

 

Also what about the dosage please ? I read 2,5mg of each is what is necessary and no side effect at even higher dosage.

 

[Turnbuckle]

I've found that 50 mg spermidine and 250 mg resveratrol (both of which induce autophagy) appear to be synergistic. Unfortunately, while I've found spermidine to be entire benign with no side effects, I can't say the same for resveratrol. Even a single dose now causes me hip pain for several days, as I became sensitized to it several years ago after taking it every day for several months. Nevertheless, I intend to keep using the combination once every couple of months, as the age reversal benefits seem worth it.