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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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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I've been taking in wheat germ for about a year. I haven't felt any side effects or seen any beneficial effects. However, something happened over the weekend. I went on a 10 mile hike with 2500ft of elevation change. The hike was about 7 hours and it was hot for half of it (about 80-85F degrees in the sun.) I was wearing a hat that covered my entire face in shade and also had 30 SPF sunscreen on. So the next day I look at my face in the mirror, and it seemed that my annoying acne scars on my forehead lightened significantly enough for me to notice! I was expecting my forehead to look even more scarred because the potential sun penetrating the hat, the thin layer of sunscreen, and my skin, which would produce melanin and darken the scars. Instead, the opposite happened. Did the spermidine in combination with a grueling hike contribute to enhanced autophagy in the face? I'm just wondering if anyone had a similar experience. By the way, in the morning I ate a keto bar with 0g of sugar and 15g of carbs and 2 soft boiled eggs. At the top of the mountain, I had about 26g of carbs (from a mixture of hashbrown, eggs, and sausage), turkey meat, and some 0 carb cheese crisps. So it was somewhat low carb and my body was probably burning a lot of fat.
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In case you missed it, this spermidine video was aired this morning by Michael Lustgarten. https://www.youtube.com/watch?v=w7lqncPch8c.
He summarizes the studies that support the conclusion that it is primarily spermidine which is the polyamine responsible for the beneficial cognitive and longevity benefits that have been demonstrated, and that spermidine is sufficient. Amounts of 1 mg/d are associated with cognitive benefits. The amount associated with life extension is about 12 mg per day. This amount could be obtained from 30 grams of wheat germ. I havent tried it, but that might be a little much to mix into a smoothie.
Since spermidine is significantly reduced by cooking at higher temperatures, I'm still looking for a simple way to get 12 mg/d from natural sources.
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I've been taking this Spermidine product for a couple of years now. https://lzrlabs.net/home-page
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This is what I have on file from vendor:
"One serving yields 1mg spermidine (some customers take up to 3 per day). Our matrix also contains several extracts from natural sources that act to support the autophagy or cell turnover promoted by spermidine and other senolytics. This greatly increases the positive effects of spermidine. Our goal with 1mg per capsule is to help people increase their daily Spermidine intake by ~15% without consuming excess calories to reach that level because maintaining a long term caloric surplus can accelerate aging drastically (exactly the opposite of what we're trying to do)."
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JFYI today I ordered some 3mg caps from these guys; spermidinepro.com . Reason being the prior vendor I was using only had about 0.3 per cap for 2/3 the price! Will see what they're like when delivered.
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https://en.wikipedia.org/wiki/Spermidine#Sources list wheat germ at 243mg / kg. So $4.50 of wheat germ is 12oz = .34kg = 83mg of spermidine.
Here's an article pointing out the apparently ridiculous prices for spermidine supplements: https://www.t-nation.com/alpha-life/the-nutrient-with-the-embarrassing-name/
I have not found information on spermidine content of wheat germ oil. I assume that, per gm, it would be higher than the wheat germ as it is an extract. So 0.5kg of Swanson oil sells for $14.30 on amazon. Also, wondering the Kretschmer Original Toasted Wheat Germ is toasted at what temp and does that destroy Spermidine? their oil is cold processed so may be better?
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24mg / 100 gm of wheat germ x 1/8 of 340gm jar of toasted wheat germ per day is about 10mg spermidina per day. Plus 1tblsp viobin oil is 15ml is 15 mg vit E -not sure how much spermidina in the oil though… 15 gms wheat germ has 2.8mg vitE == 18mg/100gm according to kretsctmer bottle, so spermidina/vitE about 1.2, i.e., 18mg spermidina assuming vitE/spermidina ratio same in wheat germ as in the oil extract. So thats 28mg per day(all mental arithmetic here..). What are clinically effective doses?
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I think you may be overestimating the amount of spermidine you are actually getting. It is reported that heating spermidine above 100 Celsius will reduce/degrade it, so who knows what is the content in toasted wheat germ, and it also impossible to know how much spermidine is in the wheat germ oil extract if it’s not indicated on the bottle. The additional processing involved would cost more and be reflected in the price.
Here is a good video by Michael Lustgarten discussing the amount of spermidine we would like to consume for anti- aging and cognitive effects:
https://www.youtube.com/watch?v=w7lqncPch8c
Lustgarten reports that in a randomized controlled trial of oldest adults at risk for dementia, a spermidine supplement of 1.2 mg/d had a positive impact on memory, and in another RCT with subjects actually suffering from dementia, supplemental spermidine of ~ 1mg/d showed a clear correlation between spermidine intake and improved cognitive performance.
For longevity effects, he indicates that if you take 30 grams of wheat germ/day you would get 12 mg of spermidine. That is the cut off for lowest all-cause mortality, the minimum for the longevity effect. He states that is also an amount associated with lowest incidence of future cognitive impairment.
If you need 30 grams of wheat germ to get 12 mg spermidine, and since a tablespoon of wheat germ weighs about 6 grams, you would need to eat about 5 tablespoons of raw wheat germ. That’s too much for me. I find that I can easily mix in 1 Tablespoon in a smoothie. Since I like wild mushrooms and aged cheddar that will give me some more, but that’s not something I could do on a daily basis.
Until someone can give me a tasty recipe as a way to consume 5 tablespoons of wheat germ daily, I will continue to settle for ~ 1mg spermidine per day.
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My favorite way to consume the wheat germ is to pour some in a bowl with walnuts, almonds any other supps, slices of banana or raisins, add water or milk. I enjoy the taste of that as cereal. chuck stanley yes, I’m not sure if spermidine is more or less fragile than vitE so my estimates are uncertain, but I guess I’m in the 10-30mg/day ballpark.
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going to try this
https://botany.bio/product/spermidine-3hcl-powder/#product-description
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A further bit of information re wheat germ oil: I asked the people at Viobin if they had any information on spermidine content, and they (very helpfully) replied that they would expect it, as a water-soluble amine, to end up in the defatted product rather than the oil extract.
I find regular wheat germ ok in a smoothie, but seem to remember reading that spermidine content is quite variable according to strain etc - no idea if this was just supplement promotion, or maybe it's a reason to go for a variety of food sources.