Spermidine, Autophagy, and the Gut-Thyroid Connection: What the Science Explores

What does spermidine have to do with thyroid health? Spermidine is a naturally occurring polyamine that helps induce autophagy, the cell's recycling process. Researchers are studying autophagy, immune signaling, and the gut-thyroid axis as interconnected areas of cellular health. This article explains those mechanisms and what current research does, and does not yet, tell us.

Interest in spermidine has grown alongside interest in autophagy, the cellular renewal process that naturally declines with age. Some of that research touches on the immune system, inflammation, and the relationship between gut and thyroid health. Below is a plain-language look at the biology involved and the state of the evidence.

What Is Spermidine?

Spermidine is a naturally occurring compound found in foods such as soybeans, aged cheese, mushrooms, whole grains, and certain vegetables. It plays a role in fundamental cellular processes, including cell growth and renewal. Research has explored spermidine in the context of the hallmarks of aging, including cellular cleanup and inflammatory signaling [1].

As one of the polyamines, spermidine is among the most studied compounds in longevity research, largely because of its established relationship with autophagy.

Autophagy: The Cell's Recycling System

Autophagy is the process by which cells break down and recycle damaged or unneeded components. It helps maintain cellular balance and is one of the ways cells respond to stress [1]. Autophagy naturally declines with age, which is why researchers study ways to support it, from fasting and exercise to dietary compounds.

Spermidine has been shown to induce autophagy in research settings, which is the main reason it appears so often in cellular-health literature. If you want a fuller picture of the process, see our guide to inducing autophagy without fasting.

Autophagy has also drawn attention in thyroid research. Studies have observed that autophagy can be disrupted in thyroid tissue under certain conditions, and that disruptions in autophagy may allow reactive oxygen species (ROS), a type of cellular stress molecule, to accumulate [2]. This is why autophagy has become an area of interest for scientists studying thyroid health.

Spermidine and Immune Signaling

In preclinical studies, spermidine has been observed to influence immune cell activity and to support anti-inflammatory pathways [3, 5]. For example, laboratory research has looked at how spermidine affects macrophages, a type of immune cell, and their inflammatory response [5].

The Gut-Thyroid Axis

The gut and thyroid are connected through what researchers call the gut-thyroid axis, part of the broader relationship between the microbiome and whole-body health [6, 8]. Gut barrier integrity, the strength of the gut lining, is one factor scientists study within this relationship, because a compromised barrier is associated with increased inflammatory signaling [7].

Spermidine has been studied for its effects on the gut in animal models, where it has been observed to support beneficial bacteria and gut barrier integrity [9, 10]. This connects to the wider research on how gut health relates to overall well-being. 

Spermidine-Rich Foods

The most direct way to increase spermidine intake is through food. Spermidine-rich foods include:

• Soybeans (and fermented soy such as natto)
• Aged cheeses (for example, cheddar and Parmesan)
• Mushrooms
• Whole grains, including wheat germ and rice bran
• Certain vegetables, such as broccoli and cauliflower

Because modern diets are often low in these foods, some people also consider a food-derived spermidine supplement, such as Primeadine®, for a consistent daily amount.

Before Adding a New Supplement

Supplements affect people differently, and benefits related to cellular processes tend to build gradually rather than appear quickly. If you have a diagnosed health condition, are taking medication, or are pregnant or nursing, talk with a qualified healthcare professional before starting any new supplement. They can advise on what is appropriate for your individual situation, including any interactions relevant to your health.

This article is for educational purposes only and is not intended as medical advice. It is not intended to diagnose, treat, cure, or prevent any disease, including thyroid or autoimmune conditions. Always consult a qualified healthcare professional before making changes to your diet, supplement routine, or treatment plan.

Age well with Primeadine®

Primeadine® is a food-derived spermidine supplement made from Japanese wheat germ. It is gluten-free, glyphosate-free, and third-party tested for purity. Primeadine offers a clean, consistent daily dose to support autophagy, cellular renewal, and healthy aging. Explore Primeadine and the Oxford Healthspan range.

References

[1] Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018). Spermidine in health and disease. Science, 359(6374), eaan2788.

[2] Tao, T., Xu, H. (2020). Autophagy and Thyroid Disease. In: Le, W. (eds) Autophagy: Biology and Diseases. Advances in Experimental Medicine and Biology, vol 1207. Springer, Singapore. https://doi.org/10.1007/978-981-15-4272-5_31

[3] Karacay, C., et al. (2022). The effect of spermidine on autoimmunity and beta cell function in NOD mice. Scientific Reports, 12(1), 4502. https://doi.org/10.1038/s41598-022-08168-2

[4] Mancini, A., et al. (2016). Thyroid hormones, oxidative stress, and inflammation. Mediators of Inflammation, 2016, 6757154. https://doi.org/10.1155/2016/6757154

[5] Liu, R., et al. (2020). Spermidine endows macrophages anti-inflammatory properties by inducing mitochondrial superoxide-dependent AMPK activation, Hif-1α upregulation and autophagy. Free Radical Biology and Medicine, 161, 339-350. https://doi.org/10.1016/j.freeradbiomed.2020.10.029

[6] Zhu, X., et al. (2024). Intestinal microbiota regulates the gut-thyroid axis: the new dawn of improving Hashimoto thyroiditis. Clinical and Experimental Medicine, 24, 39. https://doi.org/10.1007/s10238-024-01304-4

[7] Cayres, L.C.F., et al. (2021). Detection of Alterations in the Gut Microbiota and Intestinal Permeability in Patients With Hashimoto Thyroiditis. Frontiers in Immunology, 12, 579140. https://doi.org/10.3389/fimmu.2021.579140

[8] Knezevic, J., et al. (2020). Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function? Nutrients, 12(6), 1769. https://doi.org/10.3390/nu12061769

[9] Ma, L., et al. (2020). Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice. Gut Microbes, 12(1), 1-19. https://doi.org/10.1080/19490976.2020.1832857

[10] Yan, B., et al. (2023). Spermidine protects intestinal mucosal barrier function in mice colitis via the AhR/Nrf2 and AhR/STAT3 signaling pathways. International Immunopharmacology, 119, 110166. https://doi.org/10.1016/j.intimp.2023.110166