More of a summary type paper of their recent findings in Nature showing that spermidine levels rise during fasting and promotes autophage thru EIF5a. This summary argues/show the linkage to rapaymcin having a similar mechanism
https://www.tandfonline.com/doi/full/10.1080/15548627.2024.2396793
Nature paper:
Spermidine is essential for fasting-mediated autophagy and longevity
https://www.nature.com/articles/s41556-024-01468-x
Supplemental spermidine failed to increase serum spermidine levels in the ITP pre-trials according to an interview with Dr. Miller.
I’m still waiting for clarification on that issue.
There was this clinical trial of spermidine supplementation (15mg/d for 5 days) which showed most of the spermidine converted to spermine (a longer chain version). Perhaps that happened as well in the trials you mentioned?
(3) Results: Compared with a placebo, spermidine supplementation significantly increased spermine levels in the plasma, but it did not affect spermidine or putrescine levels. No effect on salivary polyamine concentrations was observed. (4) Conclusions: This study’s results suggest that dietary spermidine is presystemically converted into spermine, which then enters systemic circulation. Presumably, the in vitro and clinical effects of spermidine are at least in part attributable to its metabolite, spermine. It is rather unlikely that spermidine supplements with doses <15 mg/d exert any short-term effects."
My view and you are not going to like my reply.
Miller was wrong in his findings.
You can take it if you want but I’m not going to waste my money on supplements that most likely don’t even get absorbed.
They may not get absorbed, but what about their metabolite (s)?
Did Miller measure spermine other metabolites levels before and after?
It looks like we have more to learn about exogeneous spermidine. Recently, I began experimenting with it, taking 5 mg before bed. Mostly for fun but also because I am not a deep sleeper and I find that being aware of the Apple watch sleep metrics have led to improvements in my sleep over the past few years, I review my sleep profile each morning with my first cup of coffee.
On the very next morning after taking spermidine, my REM and Deep Sleep metrics increased by 30% and 100%, respectively. I have no independent assessment of the validity of the iPhone and Apple watch algorithms but whatever they are measuring jumped to values higher than I have recorded in about four years of tracking.
I was not expecting impacts on sleep from spermidine. In fact, I had forgot I took it and it took a few minutes to identify spermidine as the only change in my routine. Since the first day, I have experimented taking spermidine 5 mg 2-3 days in a row followed by 2-3 days off. The effects are similar to what I saw on the first day but not as pronounced. It seems unlikely that anything else has resulted in this significant change in sleep metrics.
Has anyone else observed effects of low dose spermidine on sleep patterns?
Which brand of spermidine you are using?
DoubleWood, 10 mg/two caps. 120 cap bottle. Picked it up on Amazon just to experiment.There may be better sources.
On the very next morning after taking spermidine, my REM and Deep Sleep metrics increased by 30% and 100%, respectively.
Do you feell any better because of this? If the watch hadn’t told you, would you have noticed?
That is a more difficult question to answer. I am a sceptic at heart and over a long period of time I have learned that I am not noticeably a placebo reactor but that does not rule out those kinds of effects. I am certain that I felt unusually good that first morning . . . before I made the connection. Since that time, I may have had more energy but that is speculative. The most objective indicator is better sleep metrics and by a measure unlikely to have otherwise occurred. The first night’s metrics were better than I have ever recorded since using a smart watch.
I thought this might be a new way to enhance sleep but my stats don’t show that. I have kept records of my deep sleep for 2 1/2 years on two trackers simultaneously, fitbit and oura ring. The nights after I took spermidine (that morning) I got on average about 10% less deep sleep.
I have to read it again, but I thought I read that these compounds are pro-cancer?
I found this paper difficult to unpack. Beyond the key point that OAs decline with age, is the indication of an inverted-U benefit curve for PA concentration with the right tail positively associated with cancer and the left tail positively associated with the diseases of aging. Unfortunately, I found no bread crumb trail leading to a method for assessing how much was enough, how much was too much, or a reasonable supplement dose, if any, for specific age groups, or if that might even be efficacious. Perhaps someone else has figured this out.
I am not surprised when we see these individual differences in response to a drug or supplement. Even in well controlled randomized blind experimental designs assessing the effects of a substance on a specific blood value, behavior, etc. it is common to see effects in some members of the treatment group and not others. Probability analyses determine whether the results are considered significant. Individual cases running against the findings of the sample are typically not examined. Our individual differences make it difficult for each of us to chart the smartest course for ourselves.
1 person 1 trial is pretty much meaningless, but I thought it was worth a try.
So 5mg spermidine before bed decreased my deep sleep by half. I did feel pretty rested when I awoke, though.
But thanks for posting the experience @Rob Tuck. Thats how new things get discovered.
This does not mean it doesn’t work. Disappointed they stopped the trial due to mechanistic assumption not being met.
This is an update on my observations regarding spermidine with the additional passage of time. My best judgement now is that the observed correlation between spermidine and improved sleep quality was either an artifact or an effect that does not persist with a regular dose. My sleep patterns, while generally good, are now not appreciably different from my longer term pattern.
I agree @CTStan. The research and publication culture in behavioral and medical sciences demonstrates a longstanding irrational bias against negative findings which, if you think about it, can often be reversed by changing the hypothesis. This is but one of a handful of irrational biases. When a drug produces an expected effect in only 10% of the experimental sample and not in the control sample, the results (depending on other issues such as cell size, etc.) might be judged insignificant; i.e., occurred by chance. But what would it mean for an effect to occur by chance? Sometimes a more accurate conclusion might be that this drug might be effective but only in a small percent of the population for as yet unidentified reasons. N=1 experiments like ours can be useful for raising questions, if nothing else.