A Guide To Natural Gray Hair Reversal

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.

Jan 31, 2024

By Georgia Pilling

0 comments

First signs of graying hair | Oxford Healthspan

As you probably know, gray hair is a common side effect of getting older. But why does this happen, and is it inevitable or can it be prevented and even, reversed?

To understand this process, let's start with how your hair gets its color in the first place. The roots of every hair on your head are surrounded by tissue, aka your hair follicles, which contain an abundance of pigment cells known as 'melanocytes' [1]. These pigment cells are responsible for coloring hair, producing a chemical known as melanin.

Melanin is well known for controlling your skin tone and how prone you are to tanning, but it also determines, in combination with genetic code, your unique hair color. As you age and your body struggles to keep up with cell turnover, this pool of melanocytes diminishes, in turn reducing the pigmentation supply to hair strands. Research suggests that beyond 30 years of age there is a 10-20% per decade reduction [2] in active melanocytes, resulting in the silvery/gray hair color we know well. This degeneration of the hair follicle is the consequence of both environmental and endogenous effects of aging, from sun exposure to stress levels to oxidative stress and overall biological age. And one thing these factors have in common is that they are in many cases reversible and preventable.

Causes of Gray Hair

Oxidative Stress

Oxidative stress is an imbalance between the production and accumulation of reactive oxygen species (ROS) and your body's ability to produce an antioxidative response [3]. ROS are generally produced by your body (due to your metabolism) or environmental stressors and, if levels are not controlled, can cause cell and tissue damage - in this context, to your hair follicles [4].

Stress Levels

Recent studies discuss the link between high stress levels and gray hair. Your sympathetic nervous system, responsible for your 'fight or flight response' releases the chemical 'norepinephrine' in times of high stress. This chemical release can extend to the hair follicles and be converted to hydrogen peroxide (which is what they would use in the salon to color your hair blonde!) This increased production of hydrogen peroxide can affect melanocyte stem cells, which is detrimental to the production of new pigment cells, which would come out gray or white as a result!

Vitamin & Mineral Deficiencies

Deficiencies in, for example, vitamin B12/B6, iron, vitamin D and vitamin E play a role in speeding up the gray hair process [6]. Often this is due to nutritional implications and can be restored through diet/vitamin supplementation.

Other Factors:

Certain medical conditions (e.g. autoimmune diseases, thyroid dysfunction)
Smoking
Chemical hair dye (hydrogen peroxide)
Genetic predisposition
Low glutathione levels
Poor spermidine production, which decreases with age

So, if the process behind graying hair and factors affecting it are relatively well understood, can this process be reversed or prevented?

Spermidine and Gray Hair Reversal

Spermidine, a polyamine with myriad anti-ageing properties. is a strong candidate for gray hair reversal. Emerging evidence for its ability to move hair follicles into the growth phase (where melanogenesis takes place), anti-oxidative properties, power to induce autophagy (cell renewal) and even positively affect general mood and stress levels point towards its potential to target the causative factors of gray hair listed above [6].

Increased Melanin Production

Primarily, studies have shown the potential of spermidine and putrescine (the precursor to spermidine) as a natural pigmentation agent [7], increasing melanin production from melanocytes in a dose dependant manner. Furthermore, polyamines (spermidine, spermine and putrescine) may increase melanocyte integrity and help them regenerate. They have been discussed as key mediators of cell function [8], including proliferation, migration and differentiation, which helps to prevent melanocyte depletion. Its known autophagy-inducing [9] properties add to this by helping to recycle and restore these key pigment-producing cells.

Anti-Oxidative Properties (Hydrogen Peroxide Regulation)

Regarding oxidative stress, polyamines have been shown to restore oxidative homeostasis through either acting as alternative substrates for enzymes producing ROS (suppressing ROS production) or up-regulating antioxidant systems within the body.

More specifically, spermidine and spermine have also been shown to protect against oxidative damage caused by hydrogen peroxide [10]. This protective capability was highlighted in a study with spermine- and spermidine- depleted cells showing a marked increase in sensitivity to hydrogen peroxide damage compared to cells with normal or supra physiological levels of these polyamines. This is particularly relevant when looking at gray hair reversal, showing its potential to mediate and prevent some of the factors listed above: life- and environmental- stress and chemical hair dye induced graying.

Vitamins, Mineral and Other Nutrients

If you're looking for additional, easy ways to delay the graying process, it is important to consider your diet. Particular vitamins and minerals help increase melanin production from the hair follicle, retaining your natural color for longer.

These include:

Vitamin B5, B6, B9, B12, D
Calcium
Copper
Zinc
Fish oil
Iron
Protein (Keratin)
Biotin

Plant-Derived Spermidine Supplements:

Based on this research, upping your spermidine, spermine and putrescine levels could be another great way to target gray hair...

Primeadine is a pure, wholly plant-derived spermidine supplement - Primeadine Original is made from concentrated Japanese wheat germ extract and Primeadine GF from a unique blend of Okinawan chlorella, turmeric and "Shikuwasa" or citrus lime peel. As it is food-derived, the spermidine is highly bioavailable.

Primeadine Original adds to this with a unique prebiotic fiber called FOS which reactivates your body's natural ability to make spermidine and by containing all 3 polyamines mentioned above: spermidine, spermine, and putrescine, which are involved in a virtuous recycling loop to make more of each other. Primeadine GF contains spermidine and putrescine as well as 2 other autophagy inducers and antioxidants: nobiletin and turmeric.

Attesting to this, we have valuable testimonies from our clients that have seen visible improvements in their hair, seeing new growth of colored hair strands and gray hair reversal.

If you are interested in more information for improving your hair health and seeing success stories, check out Leslie Kenny's (founder of Oxford Healthspan) youtube videos at Leslie's New Prime:

Gray Hair Reversal Success Stories with Spermidine

Gray Hair Reversal With Proof

References

[1] Nishimura EK. Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation. Pigment Cell Melanoma Res. 2011 Jun;24(3):401-10. doi: 10.1111/j.1755-148X.2011.00855.x. Epub 2011 May 5. PMID: 21466661.

[2] Anastassakis, K. (2022). The Effects of Aging on the Hair Follicle. In: Androgenetic Alopecia From A to Z . Springer, Cham. https://doi.org/10.1007/978-3-030-76111-0_8

[3] Shankar, K., & Mehendale, H. M. (2014). Oxidative Stress. Encyclopedia of Toxicology: Third Edition, 735–737. https://doi.org/10.1016/B978-0-12-386454-3.00345-6

[4] Trüeb RM. Oxidative stress in ageing of hair. Int J Trichology. 2009 Jan;1(1):6-14. doi: 10.4103/0974-7753.51923. PMID: 20805969; PMCID: PMC2929555.

[5] Watson J, Lee M, Garcia-Casal MN. Consequences of Inadequate Intakes of Vitamin A, Vitamin B₁₂, Vitamin D, Calcium, Iron, and Folate in Older Persons. Curr Geriatr Rep. 2018;7(2):103-113. doi: 10.1007/s13670-018-0241-5. Epub 2018 Apr 17. PMID: 29721404; PMCID: PMC5918526.

[6] Brito S, Heo H, Cha B, Lee SH, Chae S, Lee MG, Kwak BM, Bin BH. A systematic exploration reveals the potential of spermidine for hypopigmentation treatment through the stabilization of melanogenesis-associated proteins. Sci Rep. 2022 Aug 25;12(1):14478. doi: 10.1038/s41598-022-18629-3. PMID: 36008447; PMCID: PMC9411574.

[7] Brito S, Heo H, Cha B, Lee SH, Chae S, Lee MG, Kwak BM, Bin BH. A systematic exploration reveals the potential of spermidine for hypopigmentation treatment through the stabilization of melanogenesis-associated proteins. Sci Rep. 2022 Aug 25;12(1):14478. doi: 10.1038/s41598-022-18629-3. PMID: 36008447; PMCID: PMC9411574.

[8] Ramot Y, Tiede S, Bíró T, Abu Bakar MH, Sugawara K, Philpott MP, Harrison W, Pietilä M, Paus R. Spermidine promotes human hair growth and is a novel modulator of human epithelial stem cell functions. PLoS One. 2011;6(7):e22564. doi: 10.1371/journal.pone.0022564. Epub 2011 Jul 27. PMID: 21818338; PMCID: PMC3144892.

[9] Ghosh, I., Sankhe, R., Mudgal, J., Arora, D., & Nampoothiri, M. (2020). Spermidine, an autophagy inducer, as a therapeutic strategy in neurological disorders. Neuropeptides, 83, 102083. https://doi.org/10.1016/J.NPEP.2020.102083

[10] Liu JH, Wang W, Wu H, Gong X, Moriguchi T. Polyamines function in stress tolerance: from synthesis to regulation. Front Plant Sci. 2015 Oct 13;6:827. doi: 10.3389/fpls.2015.00827. PMID: 26528300; PMCID: PMC4602114.

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

Georgia Pilling has recently completed a degree in Physiological Science and is currently pursuing a Master of Research in Neuroscience at Newcastle University. Through her academic journey, she has formed a comprehensive understanding of underlying processes governing how our body functions, developing an interest in exploring methods to enhance these processes to improve longevity. Her specific area of intrigue is cognitive neuroscience, driven by a passion for uncovering ways individuals can optimize their brain function and overall mental well-being.

FAQs

See all FAQs or contact us!

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.

Our customer support is available Monday to Friday.Average answer time: 24h

Join us on social media to learn more!