55 replies to this topic

[lemonhead]

long thread on spermidine:

http://www.longecity...ermidine-trial/

 

Try natto or 3+ year aged cheddar for dietary sources.

Edited by lemonhead, 05 May 2014 - 03:38 PM.

[krillin]

Kismet, as usual, is the voice of informed sanity. We don't even have a mammalian lifespan study, and folks start jumping up and down for supplements.
 

Polyamines (putrescine, spermidine, and spermine) are organic compounds that are found in every living cell, where they are involved in numerous biochemical and physiological activities, including cell proliferation and differentiation (1–5). The metabolic requirement for polyamines is particularly high in rapidly growing tissues, such as during normal growth and development, and in tumors (6–8). Recent studies have suggested that reducing the amount of polyamines in cells may help to slow the cancer process (9). Clinical trials are currently underway to investigate the effect of the polyamine synthesis inhibitor, difluoromethylornithine, on cancer progression, risk for recurrent polyps, and relevant biomarkers (8). Whether foods that contribute to polyamine consumption affect cancer risk is also a topic ripe for exploration.

Until recently, it was believed that polyamines were derived exclusively from endogenous (internal) synthesis. It is now widely recognized that the polyamine body pool is maintained by three primary sources: synthesis within the body, production by microorganisms residing in the intestinal tract, and contribution from the diet (1,9–13). Studies in rats indicate that 10% of dietary putrescine, 40% of dietary spermidine, and 8% of dietary spermine are retained in body tissues (14). Thus, polyamines in the diet are among the determinants of the total body polyamine pool and may be a particularly important consideration in ... evaluating responses to pharmaceutical agents, such as inhibitors of polyamine synthesis (eg, difluoromethylornithine), which are under study in clinical trials for cancer chemoprevention. ...

This brief report describes the development of a polyamine database linked to the Fred Hutchinson Cancer Center food frequency questionnaire (FFQ). ... Of the foods from the database that were evaluated, fresh and frozen corn contain the highest levels of putrescine [per serving] (560,000 nmol/serving and 902,880 nmol/serving) and spermidine (137,682 nmol/serving and 221,111 nmol/serving), and green pea soup contains the highest concentration of spermine [per serving] (36,988 nmol/serving).

[See Table 1, Top 10 foods on the Fred Hutchinson Cancer Research Center food frequency questionnaire with the highest polyamine content](1)

See also these reports on selected polyamine contents in British and Swedish foods.

the potential protection against colorectal cancers of some nutritional factors could be associated with modifications in cellular proliferation and growth. The naturally occurring polyamines, spermine, spermidine, and putrescine, play a key role in hyperproliferation and cell migration and are involved in almost all steps of colorectal tumorigenesis. Mucosal polyamine levels, as a measurement of dysregulated hyperproliferation, have been demonstrated to be significantly associated with cancer risk and have been considered even a specific marker for neoplastic proliferation. Consequently, polyamine metabolism can be considered an attractive target for cancer chemoprevention and chemotherapy.(2)

This external dietary source provides a larger quantity of polyamines than the endogenous biosynthesis. The latter produces only about 1–2 nmol of putrescine per hour per gram of tissue in the most active organs. Diet can to a certain extent regulate biosynthesis of polyamines. Thus, dietary polyamines have several important roles to play in this regard; supporting a normal metabolism and maintaining optimal health as well as regulating the intracellular polyamine synthesis. These seem to be of importance for maintaining the normal growth, maturation of the intestinal tract. Since the level of polyamines decreases with age in animal organs (brain, kidney, spleen, and pancreas), it has been suggested that maintenance of polyamine level from the diet is important to keep the functioning of various organs in the elderly. On the other hand, the cell growth promoting effect may also be negative in relation to cancer development. It has been shown that increased polyamine levels are associated with increased cell proliferation as well as expression of genes affecting tumor invasion and metastasis (3).

The reduced levels of polyamines in aging tissues might explain the reported short-term apparent benefits in aging mice; that doesn't mean that the same benefits will accrue to taking it while young.

1: Zoumas-Morse C, Rock CL, Quintana EL, Neuhouser ML, Gerner EW, Meyskens FL Jr. Development of a polyamine database for assessing dietary intake. J Am Diet Assoc. 2007 Jun;107(6):1024-7. PubMed PMID: 17524725; PubMed Central PMCID: PMC2848593.

2: Linsalata M, Russo F. Nutritional factors and polyamine metabolism in colorectal cancer. Nutrition. 2008 Apr;24(4):382-9. Epub 2008 Feb 11. Review. PubMed PMID: 18262757.

3: Atiya Ali M, Poortvliet E, Strömberg R, Yngve A. Polyamines in foods: development of a food database. Food Nutr Res. 2011 Jan 14;55. doi:
10.3402/fnr.v55i0.5572. PubMed PMID: 21249159; PubMed Central PMCID: PMC3022763.

 

 

This paper supports Michael's argument.

 

Am J Clin Nutr. 2012 Jul;96(1):133-41.

Dietary polyamine intake and risk of colorectal adenomatous polyps.

Vargas AJ, Wertheim BC, Gerner EW, Thomson CA, Rock CL, Thompson PA.

Abstract

BACKGROUND:  Putrescine, spermidine, and spermine are the polyamines required for human cell growth. The inhibition of ornithine decarboxylase (ODC), which is the rate-limiting enzyme of polyamine biosynthesis, decreases tumor growth and the development of colorectal adenomas. A database was developed to estimate dietary polyamine exposure and relate exposure to health outcomes.

OBJECTIVE:  We hypothesized that high polyamine intake would increase risk of colorectal adenoma and that the allelic variation at ODC G>A +316 would modify the association.

DESIGN:  Polyamine exposure was estimated in subjects pooled (n = 1164) from the control arms of 2 randomized trials for colorectal adenoma prevention [Wheat Bran Fiber low-fiber diet arm (n = 585) and Ursodeoxycholic Acid placebo arm (n = 579)] by using baseline food-frequency questionnaire data. All subjects had to have a diagnosis of colorectal adenoma to be eligible for the trial.

RESULTS:  A dietary intake of polyamines above the median amount in the study population was associated with 39% increased risk of colorectal adenoma at follow-up (adjusted OR: 1.39; 95% CI: 1.06, 1.83) in the pooled sample. In addition, younger participants (OR: 1.94; 95% CI: 1.23, 3.08), women (OR: 2.43; 95% CI: 1.48, 4.00), and ODC GG genotype carriers (OR: 1.59; 95% CI: 1.00, 2.53) had significantly increased odds of colorectal adenoma if they consumed above-median polyamine amounts.

CONCLUSIONS:  This study showed a role for dietary polyamines in colorectal adenoma risk. Corroboration of these findings would confirm a previously unrecognized, modifiable dietary risk factor for colorectal adenoma. 

PMID: 22648715

[PERSONALIZEDLongevityNut]

There has been some interesting studies done on keeping one's methionine levels as low as possible in order to improve their longevity potential which may preclude the use not only of supplements containing L-Methionine and DL-Methionine, but also SAMe as well.

 

Thoughts?...

[treonsverdery]

I read a paper https://www.ncbi.nlm.../pubmed/2468644 where they gave mice arginine with lKM512 bacteria as part of a measured produced spermdne experiment.  the url is https://www.ncbi.nlm.../pubmed/2468644

 

when I read the paper I thought that 7 grams of arginine was near the beneficial mouse equivalent that is "

delays senescence in mice"  srep04548-f5.jpg   200.69KB   2 downloads

[alc]

http://cancerres.aac...2.full-text.pdf

[ta5]

2. Int J Mol Sci. 2019 Mar 12;20(5). pii: E1254.

Extracellular Spermine Activates DNA Methyltransferase 3A and 3B.

Fukui T1, Soda K2, Takao K3, Rikiyama T4.

We first demonstrated that long-term increased polyamine (spermine, spermidine, putrescine) intake elevated blood spermine levels in mice and humans, and lifelong consumption of polyamine-rich chow inhibited aging-associated increase in aberrant DNA methylation, inhibited aging-associated pathological changes, and extend lifespan of mouse. Because gene methylation status is closely associated with aging-associated conditions and polyamine metabolism is closely associated with regulation of gene methylation, we investigated the effects of extracellular spermine supplementation on substrate concentrations and enzyme activities involved in gene methylation. Jurkat cells and human mammary epithelial cells were cultured with spermine and/or D,L-alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase. Spermine supplementation inhibited enzymatic activities of adenosylmethionine decarboxylase in both cells. The ratio of decarboxylated S-adenosylmethionine to S-adenosyl-L-methionine increased by DFMO and decreased by spermine. In Jurkat cells cultured with DFMO, the protein levels of DNA methyltransferases (DNMTs) 1, 3A and 3B were not changed, however the activity of the three enzymes markedly decreased. The protein levels of these enzymes were not changed by addition of spermine, DNMT 3A and especially 3B were activated. We show that changes in polyamine metabolism dramatically affect substrate concentrations and activities of enzymes involved in gene methylation.

PMID: 30871110

[Mind]

Spermidine is possibly one of the reasons naked mole rats live so long https://www.longecit...aked-mole-rats/

[Mind]

Spermidine is possibly one of the reasons naked mole rats live so long https://www.longecit...aked-mole-rats/

[treonsverdery]

I just read a journal paper where spermidine, at .3 millimolar caused middle aged mice to live 10% longer,  https://www.ncbi.nlm...les/PMC5806691/ have 40% less of some kind of heart disease, and lowered blood pressure.  The mice drank the .3mM spermidine in their drinking water, at a human drinking 1-2L of water a day that is like 44-132mg/24 hours, but you will want to do you own molar calculations rather than believe me.

 

Spermidine is just $50-100/Kg at alibaba.com a Chinese ecommerce site I have successfully ordered things from before.  Mouse dosages are usually divided by 12.6 to come up with a human dose, so the 44-132 mg/24 hours would be divided by 12.6.  Without the mouse compensation spermidine is about 1 cent/24 hours, or with the human dose compensation 1/10th of 1 cent.

 

It is likely I will be ordering some spermidine soon.  Other than divided doses, does anyone here have advice or personal experience with spermidine supplementation?

 

[Turnbuckle]

It's also available from Amazon, but is considerably more expensive per gram. For ease of use, spermidine can be easily melted and dissolved at 10% concentration in distilled water and kept indefinitely in the fridge. With the dispenser bottle I use, 5 drops delivers 25 mg, about 2-5 times the average intake for humans found in 3 studies. See Table 3 of this study. It goes well with grapefruit juice.

Edited by Turnbuckle, 11 March 2020 - 08:57 AM.

[orion22]

sourdough bread made from sprouted wheat almost 0 gluten good taste i make it my self price almost 0 

[Harkijn]

Thanks for drawing renewed attention to spermidine,OP! Those interested in this molecule can use the search function to read back on it.

I still eat a number of spoonfuls of wheatgerm per day.

[smithx]

It's also available from Amazon, but is considerably more expensive per gram. For ease of use, spermidine can be easily melted and dissolved at 10% concentration in distilled water and kept indefinitely in the fridge. With the dispenser bottle I use, 5 drops delivers 25 mg, about 2-5 times the average intake for humans found in 3 studies. See Table 3 of this study. It goes well with grapefruit juice.

 

What bottle do you use?

 

The lowest price I found from a known-reputable supplier (after a few minutes of searching) was this:

 

https://www.alfa.com...catalog/A19096/

 

5gm / $88

 

At 25mg/d that would last a very long time.

[p75213]

Matured (12 months or more) cheddar cheese is also high in spermidine, tastes delicious, and you should never have to go to the dentist again with tooth decay.

[Turnbuckle]

Matured (12 months or more) cheddar cheese is also high in spermidine, tastes delicious, and you should never have to go to the dentist again with tooth decay.

 

 

Aged cheddar has perhaps the highest level in supermarket products, but it is not a reasonable source for most people. To get 25 mg of spermidine, you'd have to eat 120 grams of aged cheddar. Almost 500 calories.

 

See Polyamines in foods

 

Ejaculate is a surprisingly poor source. It contains about 1 mg/ml and the average ejaculate is around 5 ml. So difficult to get enough, depending on your profession.

 

Most chem supply houses won't ship spermidine to home addresses. Amazon used to, but that may have changed. 

[p75213]

I eat about 3 desert spoons of wheat germ, 3 or 4 slices of vintage cheddar cheese and about 3 tablespoons of activia yoghurt (I use 3 tablespoons of the store bought yoghurt to make 1 litre of yoghurt) per day. I read somewhere on longecity that activia yoghurt contains a bacteria (Bifidobacterium animalis) which activates autophagy.

[Harkijn]

Anyway, spermidine is a complex molecule playing various roles in a complex environment so moderation seems key. The authors in this recent study warn that both endogenous and exogenous spermidine play a role in cancer formation:

https://www.ncbi.nlm...les/PMC6796968/

[ironfistx]

I eat about 3 desert spoons of wheat germ, 3 or 4 slices of vintage cheddar cheese and about 3 tablespoons of activia yoghurt (I use 3 tablespoons of the store bought yoghurt to make 1 litre of yoghurt) per day. I read somewhere on longecity that activia yoghurt contains a bacteria (Bifidobacterium animalis) which activates autophagy.

Only that kind of yogurt you mentioned?

[p75213]

That's the only one I am aware of that has a Bifidobacterium bacteria. Google "Bifidobacterium autophagy".

[Keizo]

Aged cheddar has perhaps the highest level in supermarket products, but it is not a reasonable source for most people. To get 25 mg of spermidine, you'd have to eat 120 grams of aged cheddar. Almost 500 calories.

 

See Polyamines in foods

 

 

Looking at the table for various foods in above link... I think I'd much rather suggest broccoli or cauliflower.

 

850kcal for 10-20mg from white boiled potatoes.

250kcal for ~25mg from boiled broccoli.

250kcal for ~25mg from boiled cauliflower

(unless my eyes are making me look at the wrong lines)

 

of course you'd have to eat 1000 grams, but for some that wouldn't be much of a problem except maybe you'd get too much of some specific nutrients.

 

 

Either way considering there's quite a bit of it in normal food it makes it a bit less exciting to me as a supplement, and I wonder where the thresholds are for various effects and if the threshold for maximum good effect might be rather low and bad effects might have rather low thresholds. I just glanced over the first study in this thread so this is just half-baked thoughts. Interesting either way.

[Castiel]

Aged cheddar has perhaps the highest level in supermarket products, but it is not a reasonable source for most people. To get 25 mg of spermidine, you'd have to eat 120 grams of aged cheddar. Almost 500 calories.

 

See Polyamines in foods

 

Ejaculate is a surprisingly poor source. It contains about 1 mg/ml and the average ejaculate is around 5 ml. So difficult to get enough, depending on your profession.

 

Most chem supply houses won't ship spermidine to home addresses. Amazon used to, but that may have changed. 

But see it went from around 100~mg in fresh cheddar max spermidine to 200~mg in just one year, essentially doubling.   It needs testing but 3-4 year old cheddar could easily have 2-4 times higher spermidine than 1 year old cheddar.

[Shemp999]

Aged cheddar has perhaps the highest level in supermarket products, but it is not a reasonable source for most people. To get 25 mg of spermidine, you'd have to eat 120 grams of aged cheddar. Almost 500 calories.

 

See Polyamines in foods

 

Ejaculate is a surprisingly poor source. It contains about 1 mg/ml and the average ejaculate is around 5 ml. So difficult to get enough, depending on your profession.

 

Most chem supply houses won't ship spermidine to home addresses. Amazon used to, but that may have changed. 

Amazon does still ships this:

 

https://www.amazon.c...,aps,238&sr=8-3

[Turnbuckle]

Amazon does still ships this:

 

https://www.amazon.c...,aps,238&sr=8-3

 

 

Yes. This can be diluted in water and dosed with a dropper into grapefruit juice. See post no. 2 above. But Amazon doesn't ship it. It comes directly from RPI. Normally they don't ship to residential addresses, but last year they were making an exception for orders through Amazon. Don't know if that is still the case.

[Shemp999]

Yes. This can be diluted in water and dosed with a dropper into grapefruit juice. See post no. 2 above. But Amazon doesn't ship it. It comes directly from RPI. Normally they don't ship to residential addresses, but last year they were making an exception for orders through Amazon. Don't know if that is still the case.

I can confirm that they do ship to a residential address.  I purchased through Amazon (Prime) three weeks ago and it was delivered in 2 days via FedEx.

[TMNMK]

This may be a more vendor/retailer oriented question, but I'm curious about FWGE's such as metatrol, avemar, spermidinelife (TTL), ultra-spermidine (LZR), Lekithos, and any others anyone wants to throw out there. Does anyone have thoughts on these supplements, which one(s) they prefer and for what reasons? I know some folks are fermenting their own, but I'm not too into that for this specific substance. Further, it appears the RPI product is no longer available on Amazon which is greatly disappointing. Any other acquisition ideas would be appreciated! I'm ruling out making natto, eating enormous amounts of cheese, consuming obscene amounts of pistachios or extracting my own fermented wheat germ.

 

EDIT: well nevermind I guess.. my chem supplier has it stocked! Reagent grade spermidine trihydrochloride.

 

Nonetheless, I'm still interested in responses to this question and I'd bet others would benefit as well, so if anyone has info on the above lmk!

Edited by TMNMK, 23 April 2021 - 08:18 PM.

[TMNMK]

Btw Spermidine in health and disease