Spermidine delays aging in humans

“I use chlorella in my morning smoothie.”

Is there a brand that you prefer?

Average US intake 8mg, healthy diet estimated to contain 25-30mg, 1 cup of soy milk has ~4mg. So 1mg supplement doesn’t seem significant. Nor does the mnemonic test seem that good for measuring lifespan benefit tbh.

3 Likes

ITP stopping its test because they didn’t detect what they expected in the blood was disappointing. It could be effective by another means, or the rigor of ITP could have shown ineffectiveness which is also valuable data.

1 Like

If I recall correctly , it was 12 mg per day of spermidine that was used in studies that showed benefits. I use powder from Hansen Supplements, 12-15 mg/ day in my coffee.

Its possible that spermine, a downstream metabolite of spermidine is the key bioactive effector translating spermidine intake into physiological benefits. In that case, looking for spermidine in blood was the wrong polyamine for ITP to be looking for.

3 Likes

I mostly order Chlorella Tablets and Powder | PlantPills.co.uk but it has stock problems all the time, so I ordered some other brands as well. The study on spermidine content gave me enough confidence that any chlorella will have enough spermidine. I just make sure it is not Chinese and organic.

2 Likes

Puny amount (0.9 mg spermidine). Better to eat mushrooms.

Spermidine was present in all samples, but the fresh mushrooms contained significantly higher content of this compound than the processed samples. The level of SPD in the fruiting bodies of the brown button mushrooms was significantly higher than in the white mushroom samples (367.22 ± 14.19 and 266.47 ± 13.38 mg/kg of mushroom samples, respectively).

That is 3.67 mg per ten grams of mushrooms (367.22 / 100 grams to get ten grams).

2 Likes

a new compound to watch…

According to the study published in Nature Chemical Biology, the new classification of metabolite — acylspermidine — is produced through interactions between sirtuins and spermidines. Sirtuins are an enzyme family that is involved in many essential processes like DNA damage repair, and spermidine is a compound found in all cells responsible for life-sustaining functions. Researchers found that when the roundworm Caenorhabditis elegans did not produce acylspermidine, its lifespan decreased. This discovery helped to focus research into aging and age-related diseases like cancer, according to Prof. Robert Weiss, biomedical sciences.

The researchers first discovered acylspermidines after the Schroeder lab, led by Prof. Frank Schroeder, chemistry and chemical biology, created a version of C. elegans without the gene responsible for producing sirtuins in the mitochondria — the part of the cell responsible for energy production. This technique of removing genes is known as a knockout and is a tool commonly used to better understand the role of a particular gene.

6 Likes

Spermidine is essential for fasting-mediated autophagy and longevity

Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders. Here, we asked whether the cellular and physiological consequences of caloric restriction and fasting depend on polyamine metabolism. We report that spermidine levels increased upon distinct regimens of fasting or caloric restriction in yeast, flies, mice and human volunteers. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, nematodes and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan- and healthspan-extending effects, as well as the cardioprotective and anti-arthritic consequences of fasting. Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine–hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity.

Open Access Paper:

https://www.nature.com/articles/s41556-024-01468-x

5 Likes

I can report what is to me another interesting finding both with respect to spermidine and the use of AI LLMs. Because I actually enjoy the taste of Kretchmer’s Toasted Wheat Germ (vacuum sealed in glass bottles), I posed the following question to four LLMs. Their answers follow:

Conduct a deep search of the literature beginning with US Department of Agriculture food science data to determine if the spermidine content of wheat germ is reduced or destroyed by toasting the wheat germ.

GPT-4o (paid version)
Searched 6 sites

The available literature indicates that the spermidine content of wheat germ is significant, with concentrations reported around 2,437 nmol/g in raw wheat germ. However, toasting or other thermal processing of wheat germ can lead to a reduction in spermidine content due to the heat-sensitive nature of polyamines.

No specific USDA data is available on spermidine reduction due to toasting, but it is known that heat can affect the stability of polyamines like spermidine, which could lead to a decrease in its levels in toasted wheat germ compared to raw wheat germ. The extent of this reduction can depend on the duration and intensity of the toasting process​([Frontiers
(Frontiers | Polyamines in Food))​(
SpermidinePURE
).

For maximizing spermidine intake, using raw wheat germ or minimally processed wheat germ products is recommended. Additionally, some wheat germ concentrates, like SpermidineEVO, are marketed specifically for their high spermidine content, which suggests that stabilization techniques can help preserve spermidine even in processed forms​(

GoodMills Innovation
)​(
ETprotein
).

Gemini (paid version)
While the USDA FoodData Central provides comprehensive nutritional information, it does not specifically address the impact of toasting on the spermidine content of wheat germ. To answer your query definitively would require a deep dive into peer-reviewed scientific literature focusing on food science and the effects of heat processing on specific nutrients like spermidine.

However, based on current understanding of spermidine and its properties:

  • Spermidine is a relatively heat-stable polyamine.
  • Studies on other foods indicate that moderate heat treatments, like those used in toasting, may not significantly reduce spermidine levels.
  • Some research suggests that certain cooking methods can even increase the bioavailability of spermidine in certain foods.

Therefore, it is plausible that toasting wheat germ may not drastically reduce its spermidine content. However, to confirm this, targeted research focusing on spermidine levels in toasted versus untoasted wheat germ would be necessary.

Claude (free version)
Could not perform

Open Evidence (medical dB - registered provider version)
Sorry, OpenEvidence was not able to answer this question. OpenEvidence encountered an issue finding high-quality medical literature pertaining to the topic. This could be because existing medical literature was not sufficiently relevant to the question, because it did not meet the necessary quality threshold to be cited, or because of a temporary technical error. If you believe this is an error, please help us improve OpenEvidence and let us know at help@openevidence.com.

Observations
I do not find these variations unusual, including what might seem like a potential conflict between GPT and Gemini, both of which I find generally useful time savers in specific contexts.

4 Likes

One of the papers GPT dug up.

fnut-06-00108.pdf (599.1 KB)

2 Likes

The BB-12 strain of B.Lactis is now available in bulk quantities $261.37 for 100g (600 Billion CFU/g) from Bulkprobiotics BB-12. This seller claims they are not allowed to reveal the manufacturer they source product from, but that it is a major manufacturer that supplies bulk probiotics to many major retail brands of probiotic capsules.

3 Likes

I just found out that Nancy’s yogurt uses the BB LKM512 (BB-12) probiotic strain. But I’m not sure if they sell their products to customers overseas. If anyone has tried it before, could you share your experience?

https://nancysyogurt.com/probiotics/probiotics-in-nancys/

2 Likes

Association between dietary spermidine intake and cognitive performance in older adults: The U.S. National Health and Nutrition Examination Survey, 2011–2014

Highlights

  • This large-scale study in the elderly links dietary spermidine intake to cognitive function with robust evidence.

  • Spermidine’s cognitive benefits differ by sex, ethnicity, and BMI, favoring males and those with hypertension/hyperlipidemia.

  • The spermidine-cognition link is nonlinear, highlighting the need for balanced intake in future dietary guidelines.

Paywalled paper:

https://www.sciencedirect.com/science/article/abs/pii/S0165032725005300?via%3Dihub

1 Like

From an earlier post from Bicep, here is a US source.

Our Recipe
Cultured Pasteurized Organic Whole Milk, Pectin, Vitamin D3.

Live Active Cultures
S. thermophilus, L. bulgaricus, Bifidobacterium BB-12®, L. acidophilus, L. paracasei and L. rhamnosus.

BB-12® is a registered trademark of Chr. Hansen

Label doesn’t indicate how many billions of each bacterium the yogurt contains.

2 Likes

A new pilot study:

Effects of Spermidine-Rich Rice Germ Extract Supplement on Biomarkers of Healthy Aging and Autophagy-Proof-of-Concept Pilot Study

Background: Although epidemiological and preclinical research suggests that the polyamine spermidine improves the efficiency of autophagy, human clinical research demonstrating a specific dose of any source of spermidine capable of increasing biomarkers of autophagy is lacking.

Primary study objective: The study aimed to examine the effects of spermidine from Miricell™ rice germ extract (Nutraland USA) on biomarkers/indices of autophagy, neuroprotection, and cardiometabolic health, as well as safety and adverse events.

Methods/design: This 56-day study was conducted as a single-blinded, interventional, parallel-group, pilot trial. Vitals, diet records, and protocol compliance were recorded at weeks 0 and 8. Blood draws for cardiometabolic markers and adverse event monitoring took place at screening and weeks 0 and 8.

Setting: Conducted at a clinical research laboratory in Ohio.

Participants: Twelve (N=12) healthy men and women (age: 54.5 ± 7.9 years).

Intervention: Random assignment to 1.5 mg or 3.3 mg of spermidine daily from Miricell™ rice germ extract (Nutraland USA).

Primary outcome measures: Biomarkers of autophagy [Beclin-1 and Unc-51-like kinase 1(ULK1)], and biomarkers/indices of neuroprotection, including brain-derived neurotrophic factor (BDNF), homocysteine, and cardiometabolic health (high sensitivity C-reactive protein (hs-CRP), lipid panel).

Results: Compared to baseline, only the 3.3 mg dose of spermidine from Miricell® increased Beclin-1 by 7.3%, ULK-1 by 13.4%, and BDNF by 12.1%. Compared to baseline, the same dose resulted in a 20.8% decrease in hs-CRP, a 20.1% decrease in VLDL, and a 26.9% decrease in triglycerides. Secondary outcomes, including clinical chemistry panel, CBC, vital signs, and adverse events, reflect a good safety profile for the use of 3.3 mg/day of spermidine from Miricell®.

Conclusion: This pilot study found that 3.3 mg/day of spermidine from Miricell® rice germ extract tends to improve biomarkers of autophagy, neuroprotection, and cardiometabolic health. Appropriate follow-up studies are warranted to confirm these findings.

4 Likes

I’ll just point out that the lead author of this paper is the Chief Scientific Officer of Nutraland, the company that makes the extract tested here.

Gene Bruno, Professor Emeritus of Nutraceutical Science of Huntington University of Health Sciences, Chief Scientific Officer of Nutraland, USA.

That said, I do believe there are benefits to eating wheat germ and/or other spermidine rich foods…there’s plenty of other evidence out there.

4 Likes

Interesting pdf on their site with several pages of studies:

2 Likes

This reinforces my continued belief to keep spermidine on my supplement stack.

2 Likes

A Natural Molecule Shows Surprising Power Against Alzheimer’s

https://scitechdaily.com/a-natural-molecule-shows-surprising-power-against-alzheimers/

As people live longer, disorders associated with aging, including Alzheimer’s and Parkinson’s, are becoming more widespread. These illnesses develop when misfolded amyloid proteins accumulate in the brain and form long, fibre-like structures often compared to spaghetti. At present, no effective treatment exists that can reliably prevent or remove these damaging deposits.

Spermidine gets converted into spermine in the gut, and then this spermine is the key metabolite (of spermidine) that is actually absorbed into the bloodstream.

1 Like

Polyamines - putrescine, spermidine, and spermine - are ubiquitous cationic molecules that are essential for cellular proliferation and homeostasis. Their intracellular concentrations decline with age, contributing to physiological and cognitive deterioration. Recent studies have revealed that spermidine supplementation extends lifespan and improves cognitive and cardiac function in various model organisms, suggesting that maintaining polyamine balance has anti-aging potential. Polyamine metabolism is tightly regulated through biosynthesis, degradation, and transport; however, age-associated upregulation of spermine oxidase (SMOX) and accumulation of its toxic byproduct acrolein promote oxidative damage and cellular senescence. Suppressing SMOX activity or polyamine degradation attenuates senescence markers and DNA damage, highlighting spermine catabolism as a therapeutic target. Polyamines also modulate epigenetic regulation, including DNA methylation and histone acetylation, thereby influencing gene expression and chromatin structure during aging. Moreover, polyamine-dependent hypusination of eIF5A sustains protein synthesis in senescent cells. These multifaceted actions indicate that polyamine metabolism integrates redox control, translational regulation, epigenetic maintenance and autophagy to determine cellular and organismal longevity. While animal studies demonstrate clear anti-aging effects of spermidine and spermine, human clinical evidence remains limited, with variable outcomes likely due to bioavailability and metabolic conversion. Future strategies combining dietary or probiotic polyamine enhancement, enzyme-targeted inhibitors, and personalized metabolic interventions hold promise for extending healthspan. Collectively, maintaining optimal polyamine homeostasis emerges as a key approach to counteract aging and age-related diseases.

https://www.mdpi.com/1422-0067/24/11/9668

Several intervention strategies targeting polyamine metabolism are under investigation:

  1. Dietary and Probiotic Supplementation: Polyamine-rich fermented foods and polyamine-producing probiotics (e.g., Levilactobacillus brevis ) can increase endogenous polyamine levels (Ami et al. 2023). Modulation of gut microbiota offers a promising approach to long-term polyamine enhancement.

  2. Inhibition of Polyamine Catabolism: Targeting SMOX and PAOX may preserve intracellular spermine levels and reduce oxidative byproduct formation. SMOX inhibitors show strong potential to mitigate senescence and tissue aging (Uemura et al. 2023).

  3. Enhancement of Polyamine Biosynthesis: Upregulation of biosynthetic enzymes or supplementation with precursor amino acids may increase polyamine production, though this strategy remains in early research stages.

1 Like