Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin inhumans?

Fred Cloud Yes, redundant in the sense that they both show longevity effect and cognitive protection effect.

Is the mechanism for spermidine benefits attributable to mTOR inhibition or is there something else going on? Could it be additive rather than redundant?

chuck stanley I just meant redundant in terms of autophagy. I think rapamycin does more than just autophagy but think spermidine may only offer autophagy. I do know autophagy is beneficial up to a point and then it turns negative so more is not better and rapamycin and spermidine may be too much. All the longevity studies on spermidine are people who arent taking rapamycin.

Fred Cloud 

I see what you are saying. If we aren’t careful we could be over inducing general autophagy which could have detrimental effects. Or we could be combining compounds that target the same tissues and getting too much autophagy.

Hopefully with a multiple approach we are instead inducing selective autophagy of different targets, and providing overall long-term health benefits.

There are different modes of action between the autophagy inducers that extend healthspan and increase lifespan, at least in laboratory animals: metformin, rapamycin, resveratrol, NAD+ precursors, and spermidine all have somewhat different modes of action. Additionally, some of the other supplements we take, such as fisetin contribute to the regulation of autophagy. I sure don’t know to what extent there is overlap in the target tissues that are affected by the various approaches. So unless we have expert guidance, it makes sense to be conservative in our doses and scheduling when combining these inducers.

Fred Cloud I think the point about redundancy in multiple approaches toward the same result is an often overlooked but very important concept since redundancy can potentially be detrimental. 

But in answer to your question, I believe there is one thing that spermidine does which seems to at least be more difficult with rapamycin. How about crossing the blood brain barrier? It has been shown that spermidine crosses BBB in old mice and also in adult humans. I believe it was 1.2 mg in the study that showed cognitive improvement in adult subjects, whereas Blagosklonny cautiously increased his rapamycin dosage to 20 mg (now 24mg) biweekly, ostensibly in attempt to cross the BBB. 

chuck stanley  Unlike Rapamycin, Spermadine does not appear to inhibit MTOR, at least not according to this study:

"Autophagy is controlled by the mechanistic target of rapamycin (mTOR), which is a protein kinase complex that can determine the differentiation and function of T cells in agreement with their metabolic context39; often, the inhibition of mTOR signaling is associated with Foxp3+ Treg cell induction.40 Hence, we intended to evaluate whether spermidine was compromising mTOR signaling, similarly to rapamycin. CD4+ T cells were stimulated with spermidine or rapamycin for 1 or 2 days and stained intracellularly for S6 phosphorylation, a marker for activation of the mTOR pathway, and mTOR. Rapamycin promptly inhibited mTOR, whereas spermidine decreased mTOR signaling solely on day 1, followed by a return to control levels at day 2 (Fig 3, C and D and see Fig E8, B). This slight decrease in mTOR signaling was further observed by Western blot (see Fig E8, C)." Source: Carriche GM, Almeida L, Stüve P, Velasquez L, Dhillon-LaBrooy A, Roy U, Lindenberg M, Strowig T, Plaza-Sirvent C, Schmitz I, Lochner M, Simon AK, Sparwasser T. Regulating T-cell differentiation through the polyamine spermidine. J Allergy Clin Immunol. 2021

chuck stanley Botany.bio

chuck stanley 

I've had a few issues with them as well, some relating to things being underweight. To put such a small amount in a container loose so it all sticks on the sides is crazy. I have 2 new containers of their spermidine as well and will weigh mine to double check. They and their parent company are closing soon, and their customer service lately has been terrible. 

Hello World I've been just weighing 50mg and taking it with some food and a some other supplements. I take it about 3 times a week. 

Hello World but just tossing the powder in my mouth and washing it down with water. 

Hello World , I diluted with lactose 100:1 and add a little scoop of the mix (~12 mg spermidine) to my smoothie. It has no taste and if it sits in the smoothie for hours it still has no taste (unlike raw wheat germ which gets a little strong if it sits around).

David McCallister Why so much per day? May I ask where you got it from?

David McCallister I assume you actually mean milligrams not grams, right?

Fred Cloud no, I did not make a mistake. I mean grams. I am a member of a nootropics group who is experimenting with several things at anyone time. We have chemists who synthesize some products, doctors who advise, facilitators who make things happen including group buy ( the spermidine comes from a group buy). I plan on splitting my portion with another member in the US here who is also interested in longevity. 

David McCallister 

Extremely interesting! I’ve been wondering if there weren’t some way to organize group buys, using an escrow service, such as on Ali Baba, to hold our payments, and testing facilities for verification of product.

 Although I haven’t personally seen the rationale to consume more than 12 mg spermidine a day, (I am a fairly conservative biohacker), I would welcome an opportunity to benefit from belonging to a buyers group. Is any membership open?

Some products, spermidine, Ca-AKG, NMN, are priced pretty high for the amounts an average but conscientious experimenter would be taking.

David McCallister Why take so much? 10mg a day should be plenty but 10 grams would be 1,000 times higher dose.

Fred Cloud 

David McCallister can I ask about this group? Was it the one that got shut down by discord in the last month? These groups are where a lot of real progress is being made. 

Arizona Kid yes, it was. We’re back up and going….on our own. We will not be hosted by an outside source again