280 replies to this topic

[lemonhead]

I wanted to mention that Spermidine smells a lot like Natto. I eat Natto once per week for its polyamine content. I find it interesting that they have a similar smell.

I WISH that Natto tasted better then it does. I have to force myself to eat the stuff - and it's difficult.

...

Strangely enough, I've started to like it. I use a good amount of Coleman's mustard and San-J tamari, though (much more than the little packs it comes with).
I fix it as I've read the Japanese do for breakfast - hot rice, raw egg (pasteurized since I'm afraid of Salmonella), natto, mustard, tamari.
I might try switching from rice to barley.

[Authentic]

I'll try the mustard and Tamari, thank you for that. For my syringe I used a 5cc BD, the 1cc wouldn't have been big enough although I suppose if that's all you have access to you could just add add the water into the container first using the 1cc needle multiple times, put back into the fridge then draw the solution as needed.

I don't know if you can re-freeze it after adding water to get more than 30 days of storage, perhaps portioning. Someone else here with more expertise could you please assist (sorry).

[Turnbuckle]

I doubt that 30 days is the limit, except for scientific purposes.

[DorianGrey]

UPDATE:

I now use spermidine only a couple of times a week at a dose of 30mg in grapefruit juice, and I don't take it around the time I take C60 (2mg once a week). Spermidine appears to stay in the body for a long time (with a half-life of 22 days in mice), and thus taking it every day seems unnecessary. While the most significant change was improved skin appearance, some of this occurred just from the grapefruit juice, which contains spermidine as well as furanocoumarins. I also tried applying it to the top of my head twice (diluted 30mg to an ounce of water) where the hair growth rate is lower and thus produces an asymmetry after a few weeks. Now the asymmetry seems less, but that is purely subjective. There was no effect on gray hair that I could tell. I still note a burst of energy about a half hour after I take it. This is not dramatic, and is less than at first as I've probably built up my body stores of spermidine.

Grapefruit juice has nada spermidine, it's all putrescine. I haven't found much on the conversion rate from PUT to SPM, but conversion works also the other direction.
That's very interesting info on the half-life time. I'd like to see some evidence that cycling does some good, IMO autophagy induction would have a good effect when ramping up just once in a while. There could be a synergy with Resveratrol.

NAC is an inhibitor of mTOR, but there is literature it actually inhibits autophagy, so I wouldn't supplement it for more than a few days (e.g. great for fighting a cold). The same is true for cystine and related sulphur compounds.
People have done cycling for thousand of years when fasting once in while, but not doing CR which is not really feasible and also would have a huge impact on quality of life for most people.

Are there any studies that occasional fasting has a similar effect like long-term CR?

Edited by DorianGrey, 05 November 2013 - 02:26 PM.

[Darryl]

Plenty of animal studies compare intermittant fasting with caloric restriction. I'm not sure if there's a more recent good review than Varady, Krista A., and Marc K. Hellerstein. "Alternate-day fasting and chronic disease prevention: a review of human and animal trials." The American journal of clinical nutrition 86.1 (2007): 7-13.

[Turnbuckle]

Grapefruit juice has nada spermidine, it's all putrescine.

Are you sure it's nada? The lists I've looked at show that putrescine is higher than spermidine in fruits, typically 5 times as high, while with cheese, it's about the reverse.

Here's one source, but it doesn't specifically list grapefruit.

Attached Files

•  Foods.JPG   51.16KB   25 downloads

Edited by Turnbuckle, 05 November 2013 - 03:11 PM.

[DorianGrey]

Grapefruit juice has nada spermidine, it's all putrescine.

Are you sure it's nada? The lists I've looked at show that putrescine is higher than spermidine, typically 5 times as high, while with cheese, it's about the reverse.

Here's one source, but it doesn't specifically list grapefruit.

The source I found stated n/d (like in not detected) and they looked at about 40 different foods and also distinguished PUT, SPD and SPM, with margins or error. I was also surprised, because Wikipedia tells a different story but doesn't quantify.
They tested a juice that was sold in UK if I remember correctly, so there may be differences (shipping, processing, source) looking at other grapefruit juices, these may have some SPD content. But in conclusion, you can also drink orange juice, and that doesn't block your CYP3A4.

ps: Thanks Darryl. Intermittent (ADF) is still quite often. I had more like an occasional purge in mind, like a spring fling.

Edited by DorianGrey, 05 November 2013 - 03:25 PM.

[Darryl]

See message #110 in this thread for a list of high spermidine foods.

Edited by Darryl, 05 November 2013 - 03:28 PM.

[Turnbuckle]

The source I found stated n/d (like in not detected) and they looked at about 40 different foods and also distinguished PUT, SPD and SPM, with margins or error. I was also surprised, because Wikipedia tells a different story but doesn't quantify.
They tested a juice that was sold in UK if I remember correctly, so there may be differences (shipping, processing, source) looking at other grapefruit juices, these may have some SPD content. But in conclusion, you can also drink orange juice, and that doesn't block your CYP3A4.

Here's another source--
http://kch.zf.jcu.cz...y/2005-0564.pdf

Attached Files

•  Foods.JPG   62.3KB   33 downloads

[DorianGrey]

The source I found stated n/d (like in not detected) and they looked at about 40 different foods and also distinguished PUT, SPD and SPM, with margins or error. I was also surprised, because Wikipedia tells a different story but doesn't quantify.
They tested a juice that was sold in UK if I remember correctly, so there may be differences (shipping, processing, source) looking at other grapefruit juices, these may have some SPD content. But in conclusion, you can also drink orange juice, and that doesn't block your CYP3A4.

Here's another source--
http://kch.zf.jcu.cz...y/2005-0564.pdf

It's still a low SPD amount, you are not going to drink a liter of juice every day, so you end up with just 1-2 mg SPD/d. I estimate you can get only to about 10mg SPD via food on a healthy diet, except you eat a lot of natto or wheat germ.

To convert putrescine it requires SAMe, and that's an easily available supplement and not high cost: http://www.swansonvi...s.com/q?kw=same Maybe that's the way to go? Grapefruitjuice is loaded with putrescine, add 400mg SAMe and for a synergistic effect 100mg or 250mg Resveratrol?

"Another major role of SAM is in polyamine biosynthesis. Here, SAM is decarboxylated by adenosylmethionine decarboxylase (EC 4.1.1.50) to form S-adenosylmethioninamine. This compound then donates its n-propylamine group in the biosynthesis of polyamines such as spermidine and spermine from putrescine.^[5]"
Wikipedia.org

High polyamines seem to be also a hallmark of cancer, it's a 2011 paper:
http://www.jeccr.com...-9966-30-95.pdf
So I am not fully convinced that it's a good idea to up your polyamine intake a lot (>>25mg?) on an ongoing basis. In my imagination autophagy is like cleaning your house, either you do it on a low level but on a permanent basis or you just shift into high gear to get rid of the mess once in a while, but when it's still manageable (any thoughts?).

Because polyamines seem to promote tumor growth I would opt against the ongoing intake. Wildtype mice or rats with their 3 years life expectancy simply may not live long enough to show some of these effects when you supplement SPD. I expect that the human body would reach homeostasis after a while (weeks), just shutting down the production of enzymes like adenosylmethionine decarboxylase if not needed.

Edited by DorianGrey, 05 November 2013 - 05:43 PM.

[DorianGrey]

I doubt that 30 days is the limit, except for scientific purposes.

25% Ethanol (Vodka?) is a cheap preservative, at room temperature or in the fridge only microbial contamination would be an issue.

See message #110 in this thread for a list of high spermidine foods.

The question is, whether about 5 to 10mg/d is really high enough?
http://extremelongev...loads/natto.pdf
The paper says in C.elegans you need 29 microgram SPD/mL to extend the lifespan and lower concentration did not have such an effect (so there is no build-up i that species).
hen extrapolating to a human with just 1L of food and liquids intake this would mean about 30mg SPD per day. That's no easy target with food. You would need two glasses of grapefruit and conversion of 80% putrescine to get to that level.
I am almost tempted to say the people using 50mg SPD once a week are on the right track.

Edited by DorianGrey, 05 November 2013 - 06:22 PM.

[blood]

To convert putrescine it requires SAMe, and that's an easily available supplement and not high cost: http://www.swansonvi...s.com/q?kw=same Maybe that's the way to go? Grapefruitjuice is loaded with putrescine, add 400mg SAMe and for a synergistic effect 100mg or 250mg Resveratrol?

"Another major role of SAM is in polyamine biosynthesis. Here, SAM is decarboxylated by adenosylmethionine decarboxylase (EC 4.1.1.50) to form S-adenosylmethioninamine. This compound then donates its n-propylamine group in the biosynthesis of polyamines such as spermidine and spermine from putrescine.^[5]"

SAMe supplementation restores polyamines in depressed mice:

http://www.ncbi.nlm.nih.gov/pubmed/11742215

Neuroreport. 2001 Dec 21;12(18):3939-42.

Influence of SAMe on the modifications of brain polyamine levels in an animal model of depression.

Genedani S, Saltini S, Benelli A, Filaferro M, Bertolini A.

Source
Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, Via G. Campi 287, 41100 Modena, Italy.

Abstract

The mechanism(s) of the antidepressant activity of S-adenosyl-L-methionine (SAMe) have not yet been elucidated. SAMe is essential for the synthesis of polyamines, which have a key role in protein synthesis, cell proliferation, and neuronal plasticity. On the other hand, accumulating data indicate that depression is associated with a reduction in regional brain volume and that antidepressants increase neurogenesis in defined brain regions and also influence neuronal plasticity. Here we show that in a validated rat model of depression (chronic unpredictable mild stress-induced anhedonia) there is a significant reduction of putrescine, spermidine and spermine in the hippocampus, and of only putrescine in the nucleus accumbens septi. SAMe, at a fully antidepressant dose (300 mg/kg i.m., daily for 7 days), completely restores the levels of putrescine in the nucleus accumbens, and restores in part the levels of both spermidine and spermine in the hippocampus. These results may suggest (i) a role for brain polyamines in depression and in reward processes, and (ii) that the antidepressant effect of SAMe may be due, at least in part, to a normalization of putrescine levels in the nucleus accumbens septi.

PMID: 11742215 [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances

[timar]

Sometimes is it a good idea to carefully read a topic before engaging in discussion. Otherwise you are discussing the same issues which already had been resolved again and again...

The paper says in C.elegans you need 29 microgram SPD/mL to extend the lifespan and lower concentration did not have such an effect (so there is no build-up i that species).
hen extrapolating to a human with just 1L of food and liquids intake this would mean about 30mg SPD per day. That's no easy target with food. You would need two glasses of grapefruit and conversion of 80% putrescine to get to that level.
I am almost tempted to say the people using 50mg SPD once a week are on the right track.

Please have a look what I wrote in this very topic. It isn't hard to get 30mg of spermidine, you can get it from about 70gr of wheat germ, for example. You can drink liters of grapefruit juice, however, and it won't have any big effect on your spermidine levels because putrescine doesn't remain intact in the gut as it is broken down by the digestive enzyme diamine oxidase.

It's funny how obsessed you guys are with grapefruits. Grapefruits don't contain any more putrescine than oranges. According to some sources they contain a bit more, according to other sources they contain a bit less[2]. It's a wish-wash really. And it is completely irrelevant anyway, because as I've said, pustrescine doesn't stay intact in the human gut.

Edited by timar, 06 November 2013 - 07:18 AM.

[blood]

For those wondering if supplemental agmatine might boost putrescine (and in turn spermidine) production:

http://www.ncbi.nlm.nih.gov/pubmed/10092884

Eur J Biochem. 1999 Feb;259(3):933-8.

Agmatine modulates polyamine content in hepatocytes by inducing spermidine/spermine acetyltransferase.

Vargiu C, Cabella C, Belliardo S, Cravanzola C, Grillo MA, Colombatto S.

Source
Dipartimento di Medicina e Oncologia Sperimentale, Universitá di Torino, Italy.

Abstract

Agmatine has been proposed as the physiological ligand for the imidazoline receptors. It is not known whether it is also involved in the homoeostasis of intracellular polyamine content. To show whether this is the case, we have studied the effect of agmatine on rat liver cells, under both periportal and perivenous conditions. It is shown that agmatine modulates intracellular polyamine content through its effect on the synthesis of the limiting enzyme of the interconversion pathway, spermidine/spermine acetyltransferase (SSAT). Increased SSAT activity is accompanied by depletion of spermidine and spermine, and accumulation of putrescine and N1-acetylspermidine. Immunoblotting with a specific polyclonal antiserum confirms the induction. At the same time S-adenosylmethionine decarboxylase activity is significantly increased, while ornithine decarboxylase (ODC) activity and the rate of spermidine uptake are reduced. This is not due to an effect on ODC antizyme, which is not significantly changed. All these modifications are observed in HTC cells also, where they are accompanied by a decrease in proliferation rate. SSAT is also induced by low oxygen tension which mimics perivenous conditions. The effect is synergic with that promoted by agmatine.

PMID: 10092884 [PubMed - indexed for MEDLINE] Free full text

From the paper:

Our results show that agmatine can indeed modulate intracellular polyamine content through its effect on the synthesis of the rate-limiting enzyme of the interconversion pathway, SSAT. When hepatocytes are cultured in the presence of 0.5 m m agmatine, SSAT is induced 12-fold, as shown by the dramatic increase in its activity and by the accumulation of SSAT protein detected by immunoblotting with a specific polyclonal antiserum. This is the first demonstration of such a marked induction of SSAT by a physiological compound. The modification is accompanied by a corresponding depletion of spermidine and spermine and accumulation of putrescine and N¹-acetylspermidine. The observed increase in intracellular putrescine content could be responsible for the slight reduction in ODC activity, as it is known that this enzyme is negatively regulated at the translational level by the product of its catalytic activity [25]. Moreover, accumulation of putrescine leads to an increase in SAMDC activity through (a) acceleration of the rate of conversion of the proenzyme into the mature enzyme in a reaction that forms the pyruvate prosthetic group and (b) activation of the mature enzyme activity [26].

[Turnbuckle]

The modification is accompanied by a corresponding depletion of spermidine and spermine and accumulation of putrescine and N1-acetylspermidine.

Is this a good thing?

[blood]

The modification is accompanied by a corresponding depletion of spermidine and spermine and accumulation of putrescine and N1-acetylspermidine.

Is this a good thing?

I was assuming not. But, I'm not sure what conclusions can be legitimately drawn from an in vitro study like that.

Edited by blood, 06 November 2013 - 03:03 PM.

[Turnbuckle]

Wheat germ extracts intended for cosmetics--

PHYTOPOLYAMINE®
PHYTOPOLYAMINE® is supplied as aqueous solution of wheat germ extract.
Approximately 10% of the solution is solid ingredients. Contents of polyamines (putrescine, spermidine and spermine) are 0.05% in the solid ingredients. Other contents are proteins and sugars from wheat germ. The concentration of polyamines is at least 10 times higher than that of other wheat germ extracts.

PHYTOPOLYAMINE®-S
PHYTOPOLYAMINE®-S is supplied as aqueous solution of soybean germ extract.
Approximately 5% of the solution is solid ingredients. Contents of polyamines are 0.1% in the solid ingredients. Other contents are proteins and sugars from soybean germ.

http://www.toyobo-gl...topolyamine.htm

This gives 50 mg of mixed polyamines per kg. It ain't much!

Edit: And it's only slightly higher than raw wheat germ on a solids basis, so I don't see the value of the extract if it doesn't concentrate the polyamines.

Edited by Turnbuckle, 06 November 2013 - 03:17 PM.

[DorianGrey]

Sometimes is it a good idea to carefully read a topic before engaging in discussion. Otherwise you are discussing the same issues which already had been resolved again and again...

The paper says in C.elegans you need 29 microgram SPD/mL to extend the lifespan and lower concentration did not have such an effect (so there is no build-up i that species).
hen extrapolating to a human with just 1L of food and liquids intake this would mean about 30mg SPD per day. That's no easy target with food. You would need two glasses of grapefruit and conversion of 80% putrescine to get to that level.
I am almost tempted to say the people using 50mg SPD once a week are on the right track.

Please have a look what I wrote in this very topic. It isn't hard to get 30mg of spermidine, you can get it from about 70gr of wheat germ, for example. You can drink liters of grapefruit juice, however, and it won't have any big effect on your spermidine levels because putrescine doesn't remain intact in the gut as it is broken down by the digestive enzyme diamine oxidase.

It's funny how obsessed you guys are with grapefruits. Grapefruits don't contain any more putrescine than oranges. According to some sources they contain a bit more, according to other sources they contain a bit less[2]. It's a wish-wash really. And it is completely irrelevant anyway, because as I've said, pustrescine doesn't stay intact in the human gut.

I find 70gr of wheat germ quite high on a daily basis.

But wouldn't intestinal DAO not also react with spermidine?

You seem to be right about putrescine from juice,here a report where they have done measurements with radiolabels in rats:
http://www.ncbi.nlm..../pubmed/8912017
"Our results suggest that intestinal diamine oxidase clears the blood from diamines and prevents luminal uptake of putrescine."


Pimagedine is an inhibitor of diamine oxidase. See also http://europepmc.org...act/MED/1814681 for others. I don't think that this is really an option to enhance the putrescine uptake, also considering you see 50% reduced DAO in Crohn's Disease. Just discussing this idea here.

Competition with histamine would be another idea, but I think there are are some issues as well.

Last idea: as with all enzymes, there is a.) a limited amount of enzyme activity and b.) a certain turnover rate. Once you add more substrate, the enzyme would be overloaded and putrescine would become bioavailable, but needs to be converted (SAMe?) before it's finally cleared e.g. from plasma. The question is whether an overload of the digestive DAO enzymes is possible? If not, this whole supplementing idea would not work in human, than it's really ornithine or arginine or just high protein diet/vitamins for de-novo synthesis.

I haven't yet found real data in human (looking for a simple putrescine blood plasma curve after 240ml grapefruit).


Also thanks for the SAMe literature reference.

[timar]

I find 70gr of wheat germ quite high on a daily basis.

You forget that there are other good dietary sources of spermidine. Have a tablespoon or two of wheat germ in your yogurt, a slice of aged cheese on your whole-grain bread, a dish with tofu and shiitake, a mango and some nuts and you'll end up with plenty of spermidine.

But wouldn't intestinal DAO not also react with spermidine?

Because spermidine is not a diamine, it is a triamine and therefore DAO can't oxidize it

Pimagedine is an inhibitor of diamine oxidase. See also http://europepmc.org...act/MED/1814681 for others. I don't think that this is really an option to enhance the putrescine uptake, also considering you see 50% reduced DAO in Crohn's Disease. Just discussing this idea here.

I don't think we should think about taking DAO inhibitors when there are enough foods which have plenty of spermidine and spermine in it.

Edited by timar, 07 November 2013 - 02:53 PM.

[DorianGrey]

According to this patent application you are at least partially wrong about DAO and spermidine: http://www.patentsto...escription.html
"Native DAO, which is able to degrade other biogenic amines such as, e.g., putrescine, spermidine and cadaverine besides histamine, and which is, for instance, obtained from pig's kidney, is a homodimeric copper-containing glycoprotein in whichthe subunits are linked by disulfide bridges. "

On page 376 of this old paperhttp://www.biochemj....373/1450373.pdf you will find apparent Km values, so the DAO isn't really going after Spermidine but remember that the SPD content in food is often much lower than e.g. for putrescine.

I found this sentence from the paper a bit alerting:
"A high diamine oxidase activity in the semen together with a sufficient amount of spermine might have a deleterious effect on the motility of
spermatozoa, assuming that this combination results in a formation of the cytotoxic aldehydes."

And here's a reference about slow turnover:
http://rd.springer.c...0726-004-0070-z

"Several attempts were made to establish diamine oxidase as a regulatory enzyme of polyamine metabolism. However, diamine oxidase has a slow turnover. This, together with the efficacy of the homeostatic regulation of the polyamines via the interconversion reactions and by transport pathways renders a role of diamine oxidase in the regulation of polyamine concentrations unlikely. 4-Aminobutyric acid, the product of putrescine catabolism has been reported to have antiproliferative properties. Since ornithine decarboxylase and diamine oxidase activities are frequently elevated in tumours, it may be hypothesised that diamine oxidase converts excessive putrescine into 4-aminobutyric acid and thus restricts tumour growth and prevents malignant transformation. This function of diamine oxidase is to be considered as part of a general defence function, of which the prevention of histamine and cadaverine accumulation from the gastrointestinal tract is a well-known aspect."

My conclusion
At this point I am not sure anymore, with all the interconversion of the polyamines and unexplored effects of side-products, whether a supplementation of spermidine (like 50mg) or high intake of putrescine via food or supplementation of ornithine or arginine is really helping in long-lived human, it may also just enhance the cancer risk.
Even in C.elegans the observed effect is small, autophagy was in vitro stimulated in a type of human tumor cell and studies on centenarians may just show these people have adopted their homeostasis towards higher polyamine levels (with about half a dozen involved proteins a highly complex network).

There might be some small risk or small benefit with the high SPD content foods, but these food sources have too many other beneficial substances it's just impossible to distinguish the effect, SPD is probably flying under the radar. At least you're not having a sub-clinical deficiency in polyamines this way, so it looks okay to me to include them in your diet. From all I learned so far I won't make 70g wheat germ/day a staple in my diet now.
I've also tried some higher amounts of grapefruit juice lately when I still thought it has some SPD, but now that I know better and having tried that, I know for sure I don't like the digestive side-effects and the fact it blocks CYP3A4. For SAMe there may be some merit, but homocysteine could be an issue here, so once again there is neither enough evidence of a benefit or risk at this point. I am not a depressive rat and 300mg/kg i.v. is a huge dose, I would be very surprised if that would not restore polyamines.

Edited by DorianGrey, 07 November 2013 - 07:39 PM.

[Turnbuckle]

Another strategy to study the effects of polyamines in aging is an exogenous administration to organisms. When polyamines are provided with food or water, their endogenous levels increase. For instance, Soda et al. observed an increase in spermine after 26 weeks in mice and after two months in humans under a high-polyamine diet. We also reported that providing spermidine in food or water increased its endogenous levels in yeast, flies, and mouse liver. This is thus a promising strategy, particularly valuable in the context of extending polyamine use to humans.

http://www.impactagi...ull/100361.html

[blood]

For SAMe there may be some merit, but homocysteine could be an issue here

The examine.com SAMe page references three studies where researchers were unable to detect increases in blood homocysteine following SAMe supplementation. One of these studies involved quite high SAMe doses (1600 mg/day) taken over several weeks.

http://examine.com/s...syl Methionine/

I am not a depressive rat and 300mg/kg i.v. is a huge dose, I would be very surprised if that would not restore polyamines.

It is conceivable that relevant doses of SAMe for humans could be much smaller (per kg) than the doses used for mice and rats.

[blood]

Interesting bits & pieces:

Polyamine-rich food decreases age-associated pathology and mortality in aged mice

Kuniyasu Soda, Yoh Dobashi, Yoshihiko Kano, Shingo Tsujinaka and Fumio Konishi

The purpose of this study was to test whether oral intake of foods rich in polyamines (spermine and spermidine) suppresses age-associated pathology in aged mice. Synthetic polyamines were mixed into experimental chows, and 24-week-old Jc1:ICR male mice were fed one of three chows containing differ-ing polyamine concentrations. The spermine and spermidine concentrations in the low, normal, and high polyamine chows were 143 and 224 nmol/g, 160 and 434 nmol/g, and 374 and 1540 nmol/g, respectively. An increase in concentration of polyamine in the blood was found only in mice fed the high polyamine chow at 50 weeks of age. While the body weights of mice in all three groups were similar, the survival rate of mice fed high polyamine chow was significantly higher than those in the other two groups (p= 0.011). Mice fed the high polyamine chow analyzed at 88 weeks of age, corresponding to the end of the study, demonstrated lower incidence of glomerulosclerosis and increased expression of senescence marker protein-30 in both kidney and liver compared to those fed the low polyamine chow. As these pathological changes are associated with senescence, oral polyamine appears to inhibit the progression of age-associated pathologies.

Putrescine produces antidepressant-like effects in the forced swimming test and in the tail suspension test in mice.

Andrea D E Zomkowski, Adair Roberto S Santos and Ana Lúcia S Rodrigues
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.

Putrescine, a polyamine present at high concentrations in the mammalian brain, was suggested to play a role in the modulation of depression. Thus, this study investigated the effect of putrescine in the mouse forced swimming test (FST) and in the tail suspension test (TST), two models predictive of antidepressant activity. Putrescine significantly reduced the immobility time both in the FST and in the TST (dose range of 1-10 mg/kg, i.p.), without changing locomotion in an open-field. I.c.v. injection of putrescine (0.1-10 nmol/site) also reduced the immobility time in the FST and in the TST. The pretreatment of mice with arcaine (1 mg/kg, i.p., an antagonist of the polyamine-site of NMDA receptor) completely blocked the anti-immobility effect of putrescine (10 mg/kg, i.p.). A subeffective dose of putrescine (0.1 mg/kg, i.p.) produced a synergistic antidepressant-like effect with agmatine (0.001 mg/kg, i.p.) in the FST. Moreover, a subeffective dose of putrescine (0.01 nmol/site, i.c.v.) produced a synergistic antidepressant-like effect with arcaine (50 microg/site, i.c.v.). The results indicate that putrescine produces antidepressant-like effects in the FST that seems to be mediated through its interaction with the polyamine-site of NMDA receptors

Prog Neuropsychopharmacol Biol Psychiatry 30:8, 1419-25

Edited by blood, 10 November 2013 - 10:38 AM.

[timar]

According to this patent application you are at least partially wrong about DAO and spermidine: http://www.patentsto...escription.html
"Native DAO, which is able to degrade other biogenic amines such as, e.g., putrescine, spermidine and cadaverine besides histamine, and which is, for instance, obtained from pig's kidney, is a homodimeric copper-containing glycoprotein in whichthe subunits are linked by disulfide bridges. "

Well, it may have been an oversimplification, but DAO, as the name suggest at least has a much higher affinity to diamines than to larger amines.

Regarding the study postet by blood, we should remember that men ain't mice. Mice are largely herbivores and therefore express much less DAO than humans do.

[DorianGrey]

For SAMe there may be some merit, but homocysteine could be an issue here

The examine.com SAMe page references three studies where researchers were unable to detect increases in blood homocysteine following SAMe supplementation. One of these studies involved quite high SAMe doses (1600 mg/day) taken over several weeks.

http://examine.com/s...syl Methionine/

I am not a depressive rat and 300mg/kg i.v. is a huge dose, I would be very surprised if that would not restore polyamines.

It is conceivable that relevant doses of SAMe for humans could be much smaller (per kg) than the doses used for mice and rats.

Regarding the rat injections, I did the math: 72kg * 300mg/kg * 1 / 6 = 3.6g , and that's I.V. (injection). I think oral supplementation is already cost prohibitive in that range (even a magnitude below), not to address any other issues.
http://ncifrederick....ents/ACUC42.pdf


Thanks for the SAMe info, so if homocysteine is not a concern then SAMe supplementation looks like a good idea, it's at least safe in every other respect. I will try some sort of fasting approach with supplementation towards autophagy, so it stays on my list.

Spermidine supplementation would cost me about 1$/day at 25mg, not a huge dose. That's almost 400$/year for something that isn't even a sure thing in human. Compare the evidence to B-vitamins, vitamin D, omega-3 or alpha lipoic acid, all these supplements cost a fraction.

[timar]

Spermidine supplementation would cost me about 1$/day at 25mg, not a huge dose. That's almost 400$/year for something that isn't even a sure thing in human. Compare the evidence to B-vitamins, vitamin D, omega-3 or alpha lipoic acid, all these supplements cost a fraction.

1kg wheat germ is about 3€ (4$) here. 50gr (an amount you could mix into your smoothie for example) would provide about 20mg of spermidine + spermine, which is 20 cents a day - that is a bit more than a fourth the price. Of course, you get a lot more nutrition from that.

Edited by timar, 11 November 2013 - 10:08 PM.

[DorianGrey]

Spermidine supplementation would cost me about 1$/day at 25mg, not a huge dose. That's almost 400$/year for something that isn't even a sure thing in human. Compare the evidence to B-vitamins, vitamin D, omega-3 or alpha lipoic acid, all these supplements cost a fraction.

1kg wheat germ is about 3€ (4$) here. 50gr (an amount you could mix into your smoothie for example) would provide about 20mg of spermidine + spermine, which is 20 cents a day - that is a bit more than a fourth the price. Of course, you get a lot more nutrition from that.

It's about the same price here, but hard to get in a non-toasted version, I even went to Organic Garage and didn't see it, although they have all the other Bob's Red Mill products.. I could still get it online from Swansons and will try that.

Edited by DorianGrey, 12 November 2013 - 05:53 PM.

[DorianGrey]

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

I've seen Swanson has a variety of wheat germ oils and even soft capsules, I am wondering about the polyamine content, Google didn't reaveal much.

The oil seems to have a bunch of other benefits (huge levels of vitamin E, contains certain long-chain omega-3 fatty acids and a long-chain alcohol), but if the spermidine content is really, really high then it might be a good idea to use. People use two table-spoons, about the amount of olive oil I use per day, so a bottle should last a month or so.

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?

[timar]

I've seen Swanson has a variety of wheat germ oils and even soft capsules, I am wondering about the polyamine content, Google didn't reaveal much.

There are most certainly next to no polyamines present in the oil. Polyamines have a poor solubility in oil and are bound to the protein fraction.

The oil seems to have a bunch of other benefits (huge levels of vitamin E, contains certain long-chain omega-3 fatty acids and a long-chain alcohol), but if the spermidine content is really, really high then it might be a good idea to use. People use two table-spoons, about the amount of olive oil I use per day, so a bottle should last a month or so.

That's interesting. What long-chain omega-3 fatty acids are you talking about. Can you give a source?

[hav]

The oil seems to have a bunch of other benefits (huge levels of vitamin E, contains certain long-chain omega-3 fatty acids and a long-chain alcohol), but if the spermidine content is really, really high then it might be a good idea to use. People use two table-spoons, about the amount of olive oil I use per day, so a bottle should last a month or so.

That's interesting. What long-chain omega-3 fatty acids are you talking about. Can you give a source?

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

Much like grape seed oil, wheat germ oil is mostly linoleic which is a c18:2 pufa and which doesn't keep as well as the c18:1 oleic mufa it also contains. Olive oil on the other hand has the opposite balance with much more mufa and less pufa. I think the alcohol in wheat germ oil is an even longer 28-length carbon chain but I don't know the significance of that.

Howard