Will Spermidine Increase My Energy Levels?

Q: What is spermidine?

Spermidine is a powerful polyamine that promotes autophagy , the body’s cellular “clean-up” process, and inhibits 9 of the 12 scientifically identified root causes of aging, known as the “Hallmarks of Aging.” While two-thirds of the body’s spermidine is produced by the gut and body tissues, the remaining third comes from food. As we age, natural spermidine production declines, so maintaining youthful levels requires external sources, either from spermidine-rich foods or supplements like Primeadine.

Dec 13, 2024

By Georgia Pilling

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Spermidine and Energy Levels | Oxford Healthspan

The quest for sustainable energy enhancement has led many to explore natural compounds that might offer genuine benefits. Among these, spermidine is a particularly promising molecule, garnering attention from both researchers and health enthusiasts for its potential role in energy metabolism.

The energy crisis that many people face isn't just about feeling tired - it's about cellular vitality, metabolic efficiency, and the body's ability to maintain optimal function throughout the day. Understanding how spermidine might influence our energy levels requires a deeper look into its mechanisms and the scientific evidence supporting its use.

What is Spermidine?

Spermidine is a naturally-occurring polyamine (which is a kind of protein) found in all living cells. While first discovered in human sperm - hence its name - spermidine actually plays a crucial role in numerous cellular processes throughout the body. It's present in every cell of our body and is essential for growth, renewal, and cellular maintenance. As we age, our natural spermidine levels begin to decline, which has led researchers to investigate supplementation as a means of maintaining optimal cellular function and energy production [1].

The Science Behind Cellular Energy

At its core, energy production in our bodies is a complex process centered around cellular powerhouses called mitochondria. These microscopic structures are responsible for converting nutrients into ATP (adenosine triphosphate), the primary energy currency of our cells. This energy production process, known as cellular respiration, involves multiple sophisticated steps where mitochondria break down glucose and other nutrients to generate ATP. Through a series of chemical reactions, mitochondria create an electrochemical gradient that drives ATP synthesis. However, this delicate process can be disrupted by various factors.

Oxidative stress, which increases with age, can damage mitochondrial membranes and proteins. Environmental toxins, poor nutrition, chronic stress, and certain medications can also impair mitochondrial function [2]. Additionally, as we age, our cells accumulate damaged mitochondria that operate less efficiently, leading to reduced energy production. When mitochondrial function declines, we experience this at a systemic level as fatigue, reduced physical performance, and decreased mental clarity. This decline can create a challenging cycle where reduced energy levels make it harder to maintain the healthy lifestyle habits that support optimal mitochondrial function.

What makes spermidine particularly interesting on this topic is its ability to promote autophagy in the mitochondria, known as mitophagy. This cellular cleaning process that removes damaged mitochondria and components, helping to maintain healthy mitochondria and thus, improve energy levels [3].

The Specifics: Spermidine and Energy Production

Spermidine-Mitochondrial Connection

Spermidine is thought to play a role in maintaining and enhancing mitochondrial function through multiple mechanisms:

Basic Protection: Spermidine acts as a protective shield for mitochondria, guarding their membranes and DNA from damage. This fundamental protection helps maintain their basic health and functionality [4].
Energy Production Enhancement: Inside these cellular powerhouses, spermidine improves the efficiency of energy production processes. This optimisation leads to increased energy output at the cellular level [1].
Quality Control and Maintenance: Through promoting autophagy, spermidine helps remove damaged or dysfunctional mitochondria. This cellular housekeeping ensures that only healthy, well-functioning mitochondria remain active [5].
Creation of New Mitochondria: Beyond rejuvenating existing mitochondria, spermidine stimulates mitochondrial biogenesis - the creation of new mitochondria. This increases the total number of energy-producing units within cells [6].
Environmental Protection: Spermidine reduces free radicals (oxidative stress) in the cellular environment, creating optimal conditions for mitochondrial function. This reduction in harmful molecules further protects mitochondrial health [7].

The Combined Impact: These complementary mechanisms work together to enhance cellular energy metabolism and improve energy levels in the individual.

Physical and Mental Energy Benefits

The influence of spermidine on mitochondrial health manifests in both physical performance and mental capabilities, offering comprehensive benefits for overall vitality and longevity.

In the physical domain, research demonstrates its role in maintaining muscle fiber integrity and supporting efficient energy use within the muscles. Athletes and active individuals typically experience improved endurance during workouts and faster recovery periods between training sessions. Spermidine's ability to reduce oxidative stress is particularly valuable during intense physical activities, helping prevent excessive muscle fatigue and supporting consistent performance levels [8, 9].

On the cognitive front, spermidine's impact is equally significant, particularly given the brain's high energy demands. This stems from spermidine's ability to optimize brain energy metabolism and protect neural cells from oxidative damage. The compound's neuro-protective properties also support synaptic plasticity, contributing to both immediate cognitive function and long-term brain health [10].

The synergy between physical and mental energy enhancement makes spermidine particularly valuable for individuals seeking to optimize their overall energy performance. By supporting both muscular efficiency and cognitive function, it provides a comprehensive approach to energy enhancement that addresses the interconnected nature of physical and mental vitality.

Individual Responses and Expectations

It's important to note that individual responses to spermidine can vary based on factors such as:

Age and overall health status
Current energy levels and lifestyle
Diet and exercise habits
Sleep quality and stress levels

To maximize the energy-enhancing potential of spermidine, consider implementing these complementary practices:

Maintaining consistent sleep patterns
Regular physical activity
Balanced nutrition
Stress management techniques

These lifestyle factors work synergistically with spermidine to support optimal energy levels and overall health.

The Natural Approach to Energy Enhancement

While spermidine can be found in various foods like wheat germ, aged cheese, and shiitake mushrooms, achieving optimal levels through diet alone can be challenging. This is where Primeadine® comes in as a reliable solution for maintaining consistent spermidine levels. Primeadine® offers a high-quality, scientifically-backed food-derived spermidine supplement, visit Oxford Healthspan to learn more about how Primeadine® can support your energy levels and overall longevity.

References

[1] Madeo F, Eisenberg T, Pietrocola F, Kroemer G. Spermidine in health and disease. Science. 2018 Jan 26;359(6374):eaan2788. doi: 10.1126/science.aan2788. PMID: 29371440

[2] Brand MD, Orr AL, Perevoshchikova IV, Quinlan CL. The role of mitochondrial function and cellular bioenergetics in ageing and disease. Br J Dermatol. 2013 Jul;169 Suppl 2(0 2):1-8. doi: 10.1111/bjd.12208. PMID: 23786614; PMCID: PMC4321783

[3] Hofer, S.J., Daskalaki, I., Bergmann, M. et al. Spermidine is essential for fasting-mediated autophagy and longevity. Nat Cell Biol 26, 1571–1584 (2024)

[4] Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, Harger A, Schipke J, Zimmermann A, Schmidt A et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016 Dec;22(12):1428-1438. doi: 10.1038/nm.4222

[5] Fairley LH, Lejri I, Grimm A, Eckert A. Spermidine Rescues Bioenergetic and Mitophagy Deficits Induced by Disease-Associated Tau Protein. Int J Mol Sci. 2023 Mar 10;24(6):5297. doi: 10.3390/ijms24065297. PMID: 36982371; PMCID: PMC10049002

[6] Hofer, S.J., Simon, A.K., Bergmann, M. et al. Mechanisms of spermidine-induced autophagy and geroprotection. Nat Aging 2, 1112–1129 (2022). https://doi.org/10.1038/s43587-022-00322-9

[7] Handa AK, Fatima T, Mattoo AK. Polyamines: Bio-Molecules with Diverse Functions in Plant and Human Health and Disease. Front Chem. 2018 Feb 5;6:10. doi: 10.3389/fchem.2018.00010. PMID: 29468148; PMCID: PMC5807879

[8] Jiang D, Guo Y, Niu C, Long S, Jiang Y, Wang Z, Wang X, Sun Q, Ling W, An X, Ji C, Zhao H, Kang B. Exploration of the Antioxidant Effect of Spermidine on the Ovary and Screening and Identification of Differentially Expressed Proteins. Int J Mol Sci. 2023 Mar 17;24(6):5793. doi: 10.3390/ijms24065793. PMID: 36982867; PMCID: PMC10051986

[9] Fan J, Yang X, Li J, Shu Z, Dai J, Liu X, Li B, Jia S, Kou X, Yang Y, Chen N. Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway. Oncotarget. 2017 Mar 14;8(11):17475-17490. doi: 10.18632/oncotarget.15728. PMID: 28407698; PMCID: PMC5392263

[10] Cervelli M, Leonetti A, Duranti G, Sabatini S, Ceci R, Mariottini P. Skeletal Muscle Pathophysiology: The Emerging Role of Spermine Oxidase and Spermidine. Med Sci (Basel). 2018 Feb 14;6(1):14. doi: 10.3390/medsci6010014. PMID: 29443878; PMCID: PMC5872171

[11] Makletsova MG, Rikhireva GT, Kirichenko EY, Trinitatsky IY, Vakulenko MY, Ermakov AM. The Role of Polyamines in the Mechanisms of Cognitive Impairment. Neurochem. J. 2022;16(3):283–94. doi: 10.1134/S1819712422030059. Epub 2022 Oct 17. PMCID: PMC9575633

Georgia Pilling, BSc, Physiological Sciences (Newcastle University); MRes, Neuroscience (Newcastle University)

Georgia Pilling is a researcher interested in enhancing human longevity through optimizing physiological health and cognitive function. She holds a Bachelor's degree in Physiological Sciences (BSc) and a Master of Research in Neuroscience (MRes) from Newcastle University. Her particular area of intrigue is cognitive neuroscience, passionate about sharing practical strategies for improving brain function and overall mental well-being. In her free time, Georgia enjoys yoga, running, and experimenting with cooking.

FAQs

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What is spermidine?

Spermidine is a powerful polyamine that promotes autophagy, the body’s cellular “clean-up” process, and inhibits 9 of the 12 scientifically identified root causes of aging, known as the “Hallmarks of Aging.” While two-thirds of the body’s spermidine is produced by the gut and body tissues, the remaining third comes from food. As we age, natural spermidine production declines, so maintaining youthful levels requires external sources, either from spermidine-rich foods or supplements like Primeadine.

What are the benefits of spermidine?

Studies link higher levels of spermidine with longevity. Human trials show that food-derived spermidine supports cognition, heart health, hormonal balance, hair growth, collagen production, and nail strength, with potential benefits for fertility and circadian rhythm. These effects stem from spermidine's ability to trigger autophagy—the body's cell renewal process—and inhibit nine of the twelve "Hallmarks of Aging," including inflammation, stem cell and mitochondrial dysfunction, and gut imbalance. Clients also report deeper sleep, increased energy, gray hair reversal, improved skin, and better gut health. Read this blog post to learn more.

What makes Primeadine superior to other spermidine supplements?

While we can’t speak directly about the formulation of other spermidine products, here are some of the main differentiators of Primeadine®/Oxford Healthspan.

We source our raw materials from Japan, which is known for its Nobel Prize-winning scientific leadership on autophagy, or cell renewal. Japan has the most rigorous quality control and testing policies in the world, meaning our ingredients have the most advanced extraction process and meet the incredibly high standards of the Japan Health Food and Nutrition Food Association. They are tested for heavy metals, mold, fungi, and bacteria at the Japan Food Research Lab (JFRL), a third party independent testing lab.
Every single batch is tested for its amount of food-derived spermidine so we ensure it contains the minimum effective dose of 1mg stated on our labels.
Primeadine® is manufactured in Japan in an FDA-registered and -inspected facility with ISO22000 standards, the highest in food quality control. It is then encapsulated in an FDA cGMP facility in the USA and undergoes purity testing there as well at Eurofins or Delta.
Our capsules and tablets do not contain any synthetic ingredients, whereas other supplements typically contain magnesium stearate (of which circa 80% has hydrogenated fats in it; the supplement industry is not legally required to get rid of hydrogenated oils the way the processed food industry has been mandated by law to), shellac, talc and glycerin. Our products are all suitable for vegans. Learn more about our sourcing, quality, and testing standards.
The Primeadine® Original formulation includes a special type of prebiotic fiber, called FOS (fructooligosaccharide), that selectively feeds the friendly, spermidine-producing bacteria in the gut microbiome. The idea is to increase both supplemental, or 'exogenous' spermidine, as well as encourage your own body's natural ability to produce spermidine in your gut microbiome.
Primeadine® GF comes from a sub-strain of chlorella singled out from over 100 others because it alone contains a high level of spermidine and also contains putrescine, the precursor polyamine to both spermine and spermidine. Our chlorella is grown in the nutrient-abundant longevity islands of Okinawa, Japan, and exposed to sunlight to increase the chlorophyll and other nutrient content, such as vitamins D and K, which together help drive calcium to the bones. We combine the chlorella with two other anti-inflammatories and autophagy inducers, Okinawan turmeric and nobiletin (from Okinawan "Shikuwasa" citrus lime peel).
We do not use liposomes in Primeadine® because this is unnecessary for absorption and would prevent the benefits that happen when spermidine is exposed directly to the gut lining. There is no evidence that spermidine cannot be taken up by the cells on its own. Similar to amino acids, polyamines do not need a liposome to cross into the cell or to be taken up with epithelial cells. The process of creating a liposomal version also creates unnecessary expense.
We do not synthetically enrich our product with synthetic spermidine. Be wary of labels that say "wheat germ with spermidine" as this indicates that the wheat germ has been soaked in synthetic spermidine, thereby increasing the overall amount of spermidine but meaning it is no longer a natural source.
We do not use doses beyond what the European Food Safety Authority (EFSA) has mandated as safe for human consumption, which is 6mg daily. Please note that this is related to food-derived spermidine. Synthetic spermidine and synthetically enriched spermidine have never been tested in humans for safety or efficacy and are being sold without regulatory oversight.
We work closely with our scientific and clinical advisers at the University of Oxford and abroad, all of whom take our product and share it with their loved ones. Learn more about our scientific advisory board here.
We are also the only non-Japanese member of the Japan Autophagy Consortium, whose Senior Adviser is the 2016 Nobel Prize Winner in Medicine or Physiology, Prof Yoshimori Ohsumi, and whose Director is Prof Tamotsu Yoshimori, Osaka University. Prof Yoshimori conducted all of the mammalian research in autophagy that helped underpin Prof Ohsumi's work in yeast cells. Find out more about our story here.

What is the best spermidine dose to take?

The US FDA has not set a safe upper limit for food-derived spermidine, but the European Food Safety Authority considers up to 6 mg safe. Most studies use a daily dose of 1 mg of natural spermidine, along with spermine and putrescine, which are absent in synthetic versions. Synthetic spermidine has not been tested for human safety or efficacy.

Why is your spermidine supplement more expensive compared to other products I see on the internet?

We prioritize the highest quality, avoiding common additives like industrial seed oils, magnesium stearate, and talc often used in supplements. Unlike cheap synthetic spermidine often "cut" into products, we use food-derived spermidine sourced and manufactured in Japan under strict regulatory standards. Our products undergo rigorous third-party testing to ensure purity and effectiveness. This commitment to quality, like choosing the best ingredients for a child’s birthday cake, is our guiding philosophy.

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