Spermidine delays aging in humans

One of the papers GPT dug up.

fnut-06-00108.pdf (599.1 KB)

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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.

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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/

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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

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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.

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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.

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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.

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Interesting pdf on their site with several pages of studies:

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

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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.

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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.

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Scientists reveal why a popular anti-aging compound (Spermidine) may also fuel cancer

A molecule tied to longevity may have a hidden double life—boosting healthy cells on one hand and turbocharging cancer on the other.

Source:
Tokyo University of Science
Summary:

Polyamines—natural molecules found in every living cell—have become stars in the longevity world for their ability to boost cellular cleanup and support healthy aging. But there’s a dark twist: high levels of these same molecules are consistently seen in cancer, where tumors grow aggressively

“In normal tissues, eIF5A1, activated by polyamines, activates mitochondria via autophagy, whereas in cancer tissues, eIF5A2, whose synthesis is promoted by polyamines, controls gene expression at the translational level to facilitate the proliferation of cancer cells.”

In other words, polyamines trigger very different effects depending on which protein they influence. In healthy cells, they support cellular maintenance and energy production. In cancer cells, they help drive rapid growth.

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Can someone smarter than I am share if this is a scientifically sound article?

If so, this could be the death knell for my Blueprint Essential capsules that contains 10mg of spermidine

That multi vitamin was always a win for me because it includes so many things I’d want to take in only two pills (fewer pills and at a lower cost)

a lot of stuff can ‘delay aging’ from nmn to nr to spermidine to omega 3 to multivitamins to olive oil to orange juice to grapes to …

a lot of the same stuff can also have bad effects, for eg, if antioxidants are too high in the body (mega doses), the cells may have such low ROS that reductive stress is formed, which actually stresses the cells…of course, if one doesnt take antioxidants, the oxidative stress (ROS) may be too high, which also stresses the cells :rofl:

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I am not a massive fan of Spermidine, but I am not sure its effects either way on an exogenous basis are those significant that it does much harm. I have taken some, but at the moment I am not taking it.

Thank you Mr. Hemming :slight_smile:

I wouldn’t worry about it. Spermidine appears to have such low bioavailability that 10 mg is unlikely to have much of an effect.

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Both cautionary news, and positive news, on spermidine in this new paper:

Having established that polyamine depletion sensitizes cells to ferroptosis, we sought to determine the underlying mechanisms. Interestingly, while our data demonstrate that polyamine depletion sensitizes cells to ferroptosis, recent studies have shown that excess intracellular polyamines can also promote ferroptosis40,46. Excess spermidine and spermine are catabolized by the enzymes spermine oxidase (SMOX) and polyamine oxidase (PAOX), which convert them into lower-order polyamines such as putrescine while generating hydrogen peroxide and reactive aldehydes as byproducts6. These reactive intermediates can propagate lipid peroxidation, thereby sensitizing cells to ferroptotic cell death40,46. Consistent with this biphasic effect, we found that high-dose spermidine supplementation (100 μM) increased susceptibility of GPX4 inhibition. In sharp contrast, lower concentrations used in our rescue experiments (10 μM), which are closer to the physiological extracellular levels47, were protective (Figure 3A). These findings suggest that both polyamine excess and deficiency can sensitize cells to ferroptosis, albeit through distinct biochemical routes, underscoring the importance of maintaining polyamine homeostasis.

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This is a preprint derived from other sources. If it holds up, it is useful information. There is no direct translation but a reasonable inference for diet and supplementation is that a typical diet might not want to supplement dietary sources (wheat germ, legumes, mushrooms, aged cheese, natto/tempeh, and other fermented foods) with more than 5 mg/day. Doublewood offers 5 mg capsules.

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