Spermidine - any evidence to show it actually works?

I believe this was being promoted a lot over a year ago by a number of influencers. Now time has passed, do you still consider that it’s a useful supplement to take and have their been any new larger studies to show it does anything at all?

1 Like

I don’t think there is adequate evidence that taking Spermadine supplements will help you.

It’s one of those moonshot supplements that is probably at worst harmless. I mean, it’s essentially just wheat germ.

If it has a positive effect, great. If not, no harm is done. The only side-effect is a lighter wallet.

It’s supposed to promote autophagy, so I take it on the first three days to boost the autophagic effects of Rapamycin. Does it work? No clue. It’s a moonshot.

1 Like

Thanks for letting me know this. I checked that out and as I already take a tablespoon of wheat germ each day so I believe that provides me with enough spermidine.

Spermidine is very concentrated. You’d have to take a very large dose of wheat germ to get the same effect.

See the table below.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022763/table/T0001/?report=object only

Highest scorer (mean values) was dried soybeans, at 207 mg per 100 gm. Next is aged (for at least one year) cheddar at 199 mg per 100 gm. Cheddar is more palatable (to me) than wheat germ.

Costco sells cheap three-year aged cheddar.

This was discussed in an earlier thread. You can get member insights there:

Thanks for your advice. Do you have any idea of the amount of spermidine that is currently being recommended to help with longevity?

No larger trials yet I don’t think. Small trials and invitro studies, so far. There are some interesting studies going on in Germany / Austria but will take a few years to see results I think.

As you may have heard, Richard Miller / the NIA ITP tried to evaluate spermidine for lifespan improvement and did 6 months of testing on mice, but could never detect any increase in blood levels of spermidine despite feeding the mice the recommended dosing of spermidine (from the spermidine researchers) - so they gave up on it. So, the results of spermadine are still very much “mixed”.

You can do a search on our site to see all the news posted on spermidine so far:



The Europeans made the following finding:

Spermidine supplementation using the spermidine-rich plant extract did not significantly alter whole-blood polyamine concentrations in humans and mice at most concentrations. The absence of changes of polyamine levels in the blood may be due to the fast absorption/metabolism rate of polyamines from the intestinal lumen into solid tissues, as observed in an ex vivo rat model by Uda and colleagues [18].


The Japanese, on the other hand, state the following:

Although the blood spermidine/spermine ratio in mice did not change after increased polyamine intake, this ratio did decrease in human volunteers. The difference in blood spermidine/spermine ratio between mice and human volunteers might be due to a species difference, differences in the ratios of spermine/spermidine loaded, and differences in the intestinal environment such as endogenous flora.


Same findings as Miller, with regard to mice, and spermidine in blood.

The above also shows differing conclusions of the Europeans versus the Japanese. The Europeans think it is the fast absorption/metabolism rate that makes it hard to detect in blood. The Japanese posit that it is a specie difference between mice and humans, that explain their findings - spermidine increase in humans, no change in mice.


Other researchers, instead of focusing on blood levels like Miller, look to effects, after spermidine supplementation.

Lifespan extension in mammals

Lifelong spermidine supplementation via drinking water is sufficient to prolong the lifespan of adult female and male mice90. Similar effects were observed for spermine but not for putrescine90.

Spermidine also sufficed to prolong the lifespan of pre-aged 18-month-old mice90 and short-lived male mice with progeria (Zmpste24 −/− mice)171.

Likewise, daily injections late in life caused a nonsignificant lifespan extension in mice102 and polyamine-enriched food prolonged the lifespan of aging mice172, suggesting that the mode of administration is of little importance for the longevity effects.

Interestingly, the upregulation of intestinal polyamine production in 14-month-old mice by feeding the prebiotic arginine combined with the probiotic bifidobacteria LKM512 (equipped with the enzymatic machinery to convert arginine into spermidine) is sufficient to prolong lifespan and reduce the incidence of age-related diseases173,174.

While the cardioprotective effects of spermidine could mechanistically be linked to autophagy90, only one mechanistic lifespan study has been conducted in mammalian models. In the study by Yue et al., lifespan extension and autophagy induction by spermidine feeding were abolished in autophagy-deficient male Map1s-knockout mice52.

Fewer studies have been carried out on rats: in salt-sensitive Dahl rats, spermidine exerts systemic cardioprotective effects90. One study found no impact on life expectancy but a significant healthspan-extending effect in middle-aged male Sprague-Dawley rats175.


LKM512 again. Seems to be a good supplement.


Healthy human male volunteers added 50 to 100 g of the polyamine-rich fermented soybean prduct, natto, to their daily intake. After 25 wk, the meand blood spermine concentration in mice receiving the test diet with high polyamine concentrations was 10.1 ± 2.4 umol/L, while the mean concentrations found in mice fed with a diet with normal or low polyamine concentrations were 5.2± 0.9 and 4.7 ± umol/L, respectively.

Was wondering why the Japanese measuring spermine, not spermidine.

Dr. Richard Miller - “a metabolite that spermidine gets converted into, spermine”

at 26:59

1 Like