Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin inhumans?
My wife and I eat natto (fermented soybeans) daily which contains a relatively large amount of spermidine.
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Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin inhumans?
Autophagy. 2019; 15(1): 165–168.
Published online 2018 Oct 11. doi: 10.1080/15548627.2018.1530929
ABSTRACT
Spermidine is a natural polyamine that stimulates cytoprotective macroautophagy/autophagy. External supplementation of spermidine extends lifespan and health span across species, including in yeast, nematodes, flies and mice. In humans, spermidine levels decline with aging, and a possible connection between reduced endogenous spermidine concentrations and age-related deterioration has been suggested. Recent epidemiological data support this notion, showing that an increased uptake of this polyamine with spermidine-rich food diminishes overall mortality associated with cardiovascular diseases and cancer. Here, we discuss nutritional and other possible routes to counteract the age-mediated decline of spermidine levels.
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Another article:
Cardioprotection and lifespan extension by the natural polyamine spermidine
Nat Med. 2016 December ; 22(12): 1428–1438. doi:10.1038/nm.4222.
AbstractAging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for the protection from cardiovascular disease
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Thank you David. I think spermidine needs a thread on its own. I started with spermidine one week ago so it is too early to say anything about it besides the acute effects. I practice intermittent fasting and lunch is my first meal of the day. I exercise in the mornings. I mostly run and do some exercises for strength. My “acute” experiences of spermidine this far are that I have gotten much more sore in my q-ceps after intense running.
This is an experience that I only have gotten before when I have combined intense exercise with an El Mayo style Fisetin session.
I speculate that this soreness after intense exercise might be related to increased autophagy. I have previously exchanged similar kind of thoughts related to the use of fisetin with @david_c
I will keep posting my thoughts and my experiences of spermidine in this thread.
May I ask what brand of Spermidine you use now. Are you still using Primeadine?
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Staffan Olsson I am using Primeadine and my wife will start using Primeadine soon, as soon as she finishes our supply of spermidine life. Our youngest son is also taking Primeadine, which we bought for him.
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David H Now I have been eating spermidine capsules for approx 6 weeks. Brand - Aenutri 1 mg/day. I am 58.
If someone decide to start with spermadine, I would suggest to take pictures of hair and nose. This because I think I have gotten less grey hair since I started with spermadine. I would love if I had taken "before" pictures. Placebo? Honestly I dont know. Btw, I have thin very short hair, 2-4 mm.
I have also noticed that the pores on my nose seem less visable or smaller. And I do not do any other treatments focusing on skin or hair.
I would love to hear from people that start eating spermadine. Are my observations unique?
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Staffan Olsson I added Spermidine to my stack about a year ago.
https://lzrlabs.net/order-37061865
My hair is far less grey than my peer male friends my age, but hard to associate it with Spermidine, genetics, or the buffet of other interventions undertaken.
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Staffan Olsson I agree I also *think* I have darker hair, and I have some very slight hair regrowth. But by the time I noticed this AKG and NAD boosters are also in the mix with spermidine so I cannot pick the agent apart from these others.
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Jack Black
Thank you for your feedback on spermidine.
Yes, I have noticed a minor hair rejuvenation. A few days ago my daughter said “I see more hair growing on your head”. Besides myself, my daughter is probably the only one that has noticed this effect. So the effect I notice is not a meaningful change in my appearance.
I see some research indicating that the effect that I experience is a real effect and not a creation of my imagination.
I have been on spermidine for a few months. I must mention that I have also included AKGy, but in the form of Arginine Alpha-ketoglutarate. (I intend stop taking AAKG and start with Creatine Alpha-ketoglutarate instead).
BTW my experiment with AAKG have resulted in Increased muscle strength, especially when I take it in combination with citrulline. (3-4 gr of each).
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Em Mmn
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I've been looking into obtaining a Spermidine supplement on the Internet. (I had previously bought a rather expensive one that doesn't actually state how much Spermidine is in it.) I have tabulated my search results on the following spreadsheet, where "Conc" means Spermidine content of one capsule:
Brand Product # mg Conc (mg) Price SuperSmart Spermidine 60 150 1.50 $89.00 Lekithos Spermidine 120 525 0.18 $59.99 Primeadine Spermidine 90 300 0.33 $95.00 Swanson Wheat Germ Oil 60 1130 3.28 $4.83 Swanson does not promote the Spermidine concentration of their Wheat Germ Oil supplement, but after consulting with their Customer Support group, I concluded that it should be about 3.3 mg per cap. I just ordered 5 bottles.
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JGC Great research John. Whats suspiciously absent with all this promotion of spermidine benefits lately is dosage. I suspect this means most products arent supplying an effective dose so they leave that part out. I have done a little bit of research but not turning up much, perhaps we don't really know yet and things are simply not firmed up yet. Do you have any guidance on dose?
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Fred Cloud
I looked at an article in Nature Medicine on the effects of Spermidine on heart health and longevity in mice and also at the Supplementary Information that is linked to the paper. For some reason, the authors never give any indication of how much Spermidine they are actually giving the "Spermidine" mice they are treating. They do say that Spermidine is added to the drinking water, so perhaps the dose depends on how much the mice drink. The Supplement goes into how much polyamine (i.e. Spermidine and related compounds) is in different foods (with wheat germ as highest at 2,440 nmol/g), but it isn't specified how much of what the mice are eating.
The pill peddlers seem to want you to take enough of their capsules per day to get about 3 mg or so of Spermidine. That matches well with the estimated content of one Swanson Wheat Germ Oil capsule, so we will probably take one of those every evening at dinner.
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Fred Cloud
I improved my spreadsheet with more suppliers, links to them, and an extra column giving the price per mg that each one is selling their Spermidine for, sorted from highest to lowest. The LRZ Labs product (which we have been taking recently) doesn't give their Spermidine content, so I estimated it. The SuperSmart product uses rice extract rather than wheat germ and claims to have "standardized" it to 1% Spermidine.
Brand
Product Name
#
Total
(mg)
Spermidine
(mg)
Price
$/mg
Oxford Healthspan Primeadine Spermidine 90 300 0.33 $90.00 $3.03 Lekithos Spermidine 120 525 0.18 $59.99 $2.78 Longevity Labs SpermidineLIFE 60 800 1.00 $99.00 $1.65 LRZ Labs Ultra-Spermidine 40 700 0.80 (est) $43.97 $1.37 SuperSmart Spermidine 60 150 1.50 $89.00 $0.99 Swanson Wheat Germ Oil 60 1130 3.28 $3.56 $0.02 As for dosage, I found an NIH Trial entitled "Polyamine-enriched Diet in Healthy Older Adults With Subjective Cognitive Decline (preSmartAge)" in which the human trial subjects are being given either 750 mg of polyamine-rich plant extract per day or the same amount of potato starch as a placebo. That's roughly equivalent to the capsule content of the products above.
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JGC
I found this, it’s in German and it shows great variability when it comes to spermadine content.
Can it be spermadine life promoting their own brand? If it is part of a promoation then the question is if the promotion is done in an unethical way?
Spermidingehalt von Weizenkeim-Produkten - spermidin.health
I have not yet bought spermadine life. But that’s the one I consider to be my next spermadine product. They have good scientific backing and they rely on cooperation with a few universities.
but I would really like to find a cheaper alternative.
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Staffan Olsson
Interesting writeup, but perhaps self-serving.
The person I contacted in Swanson Customer Support did warn me that Swanson had never assayed the Spermidine content of their wheat germ oil. The calculation from which the 3.28 mg estimate came used the Spermidine content of wheat germ, the fraction of oil extracted from the solid, and the oil content of the capsules.
The implicit assumption was that all the Spermidine in solid wheat germ goes into the oil. Does anyone know if that's a good assumption? I note that Swanson's product is cold pressed, which might aid in retaining the Spermidine.
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JGC I noticed that the folks over at Longecity experiment with dosages starting at 25mg/d all the way to 100mg/d from RPI Spermidine (which used to be for sale on Amazon).
What you guys made you shoot for 3mg/d instead?
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aribadabar
Can you provide a link to the experiment that describes those doses? I've had a lot of trouble finding such information, and the paper I did find (see above) used much smaller doses.
Also, are you sure the 100 mg wasn't the dose of wheat germ extract containing a smaller amount of Spermidine? As I said above, all of the commercial Spermidine pill peddlers are specifying daily Spermidine doses around 1-3 mg.
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JGC I was primarily referring to the discussion in this thread: http://www.longecity.org/forum/topic/63334-spermidine-trial/
And here is a person doing 100mg/d for a year: https://www.longecity.org/forum/topic/98495-im-ordering-spermidine/?view=findpost&p=902706
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aribadabar
OK, I looked at the thread. While it's good that the adventurous guy who was taking 100 mg/day didn't suffer any bad side effects, he also "didn't notice anything" in the way of benefits.
As somebody on the thread said, lower doses at the level of 1.5 to 6 mg/day have been reported to provide benefits. Perhaps when our Wheat Germ Oil order arrives, we'll up the planned dosage to two caps per day with meals for 6.5 mg/day.
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JGC To put things into perspective, 1mg spermidine is the amount in typical 5ml ejaculate (ostensibly a small amount of body fluid and therefore the optimal spermidine body content is a lot higher).
The polyamine depletion with age looks a bit more significant than 1-5mg/d could counteract.
I don't think it is in the same league as Rapamycin where 1-2mg is the difference between goldilocks and overdosing (and it is showing definitively as canker sores)
OTOH, spermidine can work quietly "behind the scenes" and since even 100mg/d didn't show any (even adverse) effects means that 1-5mg most probably won't do anything significant.
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JGC How does Swanson softgels compare with Swanson Wheat Germ Oil 16 oz for 14.31 on Amazon? The oil is viobin - cold processed, vs softgels - cold pressed. I assumed the processing included the pressing and so ordered the 16 oz bottle..
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JGC I know this is an old post, but I'll still ask my question. Where did you find information about the spermidine content of Swanson Wheat Germ Oil capsules to be around 3 mg? I asked Swanson a few months ago about this, but never received an answer, and my research indicates that spermidine is not oil soluble. Thanks.
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Jay Orman
OK, here's where my number of about 3 mg /cap came from. In June 2021 I corresponded by email with one Mary L. , who is a Product Specialist for Swanson. She wrote me the following:
"Data online from multiple citations suggests that wheat germ has 243 mg spermidine/ kg of wheat germ. This would be 0.243 mg spermidine/gram of wheat germ or 243 mcg spermidine per gram of wheat germ. Online nutrition data suggests that wheat germ has 9.7 grams fat per 100 gram wheat germ. This would be 0.097 grams or 97 mgs of fat per 1 gram of wheat germ . Calculating spermidine percentage in wheat germ oil, using wheat germ data and oil content of wheat germ:
(243 mcg spermidine / gram wheat germ )(1 gram wheat germ/97 mg fat) = 243 mcg spermidine/97 mg fat."The Swanson Wheat Germ Oil caps contain 1,310 mg of wheat germ fat. From this, I calculate: 1,310 mg*(0.243 mg/97 mg) = 3.282 mg. That means that the spermidine content of one Swanson cap should be about 3.28 mg. Admittedly, that calculation assumes that all of the Spermidine in a gram of wheat germ is present in the 97 mg of wheat germ oil extracted from it, but I have no reason to believe that, if cold pressing works as described, that is not the case.
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JGC Excellent answer. Thanks.
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Jay Orman
Oops! I just looked at the bottle label, and Swanson's Wheat Germ Oil contains 1,130 mg of wheat germ oil (not 1,310 mg). That calculates to 2.83 mg of Spermidine per capsule. I guess that's still about 3 mg/cap, which is the number I stated. Sorry for the digit transposition.
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JGC Well, I've investigated this a few times over the last year, but I always hit the problem of spermidine not being oil soluble. So, I don't see how it could be present in wheat germ oil even if it is cold pressed. My latest check at Sigma Aldrich ( https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/867/781/s4139pis.pdf ) indicates that spermidine is soluble in water (50 mg/ml), ethanol, and ether which simply confirms what I've read before. It would be great to find a Certificate of Analysis that shows spermidine's presence in wheat germ oil, but I haven't found one of those. Of course, my thinking on this could certainly be wrong.
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Jay Orman
You may be right, and it's a question that can only be really answered by a chemical analysis. My model is that in cold pressing, whatever liquid is in the wheat germ, mostly oil, is collected, and spermidine comes out with the water-based part of that liquid. If the collected liquid all goes into the capsules, then they should contain spermidine.
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