Spermidine and COVID-19: supplements for improving immune health

After almost two years of the coronavirus pandemic, the ongoing demand for effective treatments has been largely unmet and a cure for COVID-19 remains elusive. Spermidine supplements may play a part in immune health; studies investigating the impact of spermidine on the COVID-causing SARS-CoV2 virus found that the longevity-boosting polyamine can increase autophagy and reduce viral replication in infected cells, offering a potential COVID-19 therapeutic.
Longevity.Technology: Despite wide vaccination coverage in most high-income countries, Omicron has become the latest addition to the lineage of COVID-19 variants and research into potential coronavirus therapeutics is therefore increasingly important. A relatively new player on the longevity scene, spermidine is fast-becoming a popular dietary supplement that benefits health and longevity. While not a cure-all, it does mimic the effects of other life-extending interventions like calorie restriction, using the cellular stress response to keep cells healthier, improve brain function and keep your body ticking. Spermidine and the SARS-CoV2 virus (as well as aging) seem to be linked via autophagy, the process of cellular renewal that spermidine induces and SARS-CoV2 reduces, an association that has been investigated in the hope of potentially improving COVID-19 vaccine efficacy and treatments.

Originally found in semen (hence the name) spermidine is a polyamine found in all eukaryotic cells and the majority of human tissues.

What is spermidine?

Originally found in semen (hence the name) spermidine is a polyamine found in all eukaryotic cells and the majority of human tissues. It plays a central role in regulating cell metabolism and induces autophagy, the process by which cells reuse their damaged organelles to achieve cellular rejuvenation. Autophagy is always active in most types of cells where it plays a housekeeping role by maintaining intracellular organelles. It is also used to balance energy sources in response to nutrient stress and therefore can be induced by fasting [1]. The health and longevity benefits of caloric restriction through fasting have been well-studied. However, since few people are able to commit to fasting for prolonged periods of time it is a difficult lifestyle to sustain. Alternatively, caloric restriction mimetics (CRMs) like spermidine can be used to simulate the effects of fasting on the body without the negative side effects of hunger and lethargy that can accompany conventional fasting. Taking spermidine supplements tricks the body into a fasting state, thus inducing autophagy and protecting against age-related diseases including cancer, metabolic disease, heart disease and neurodegeneration [2]. Spermidine can also increase longevity by preventing telomere shortening and stabilizing mitochondrial DNA, which both contribute to cellular aging [3].
As we age, the body’s spermidine levels naturally decrease, inhibiting cellular renewal and furthering aging. Spermidine is naturally present in the human diet and it is possible to increase your intake by eating common whole foods high in spermidine such as wheat germ, soybeans, nuts, and some fruits and vegetables. Spermidine is even more concentrated in soybean products like shiitake mushrooms, amaranth grain, and durian [4]. However, the most effective way to increase your spermidine intake is through dietary supplements. Learn more in Longevity.Technology’s FREE Longevity supplements industry report.

Supplements and the immune system

Spermidine supplements offer protection against age-related illnesses that are becoming increasingly prevalent amongst the global aging population. It additionally has the potential to be used against emerging viruses such as SARS-CoV2. The COVID-19 pandemic has renewed interest in dietary supplements and their effects on the immune response with the hope that they might help the immune system protect against SARS-CoV-2 infection and reduce the severity of resulting COVID-19 disease. The body’s immune system defends against disease-causing pathogens by using innate responses that form the first line of defence, and adaptive responses that are engaged later. The innate immune system uses physical barriers like the skin and gut epithelium to prevent pathogens from entering the body, while the adaptive immune system uses leukocytes (white blood cells) as a cavalry to identify and eliminate pathogens in the body. A side effect of this is increased inflammation, which while eliminating the pathogen, also causes symptoms such as swelling, heat, pain, loss of tissue function and severe pathology. This is evident in those suffering with severe COVID-19 cases. Autophagy works as part of both of theses immune systems, clearing away pathogens and regulating inflammation.
Self-medicating with dietary supplements to enhance immune function and reduce inflammation has increased during the pandemic and has some scientific basis. Several vitamins and minerals found in supplements such as vitamin C, vitamin D, and zinc are required for effective immune functioning, while nutrient deficiencies can increase susceptibility to infections. Supplements can also help to prevent and reduce symptoms of common respiratory illnesses such as the cold and influenza, with the thinking being that this could potentially be transferred to symptoms of COVID-19. However, the effect of supplements on the immune system has not yet been studied in COVID-19 patients so there is no empirical evidence proving that supplements are efficacious in preventing or treating COVID-19. Measuring the impact of the active ingredients found in supplements on the immune system would be difficult anyway as the system involves a complex matrix of different organs, tissues and cells [5].

The introduction of different COVID-19 vaccines and subsequent boosters has provided the majority of people in high-income countries with protection against serious illness or death from coronavirus.

Spermidine and improved vaccine efficacy

The introduction of different COVID-19 vaccines and subsequent boosters has provided the majority of people in high-income countries with protection against serious illness or death from coronavirus. However, vaccines are generally less efficacious in older adults and the immune system becomes less efficient and more susceptible to infection with age. This is a process known as immunosenescence and may be related to autophagy. Indeed, the majority of severe COVID-19 cases and deaths have occurred in older people. To counteract this, a preliminary study investigated whether spermidine supplements increased vaccine efficacy in older subjects [6]. Researchers found that endogenous levels of spermidine in human T cells (a type of leukocyte essential in the immune response) decreased with age. Supplementing the T cells with spermidine restored autophagy level and function. This discovery could inform future trials that use autophagy-boosting compounds like spermidine to improve vaccine efficiency in older adults.

Treating COVID-19 with spermidine

There are some pharmacologic treatments available to manage coronavirus symptoms in those at high risk of serious illness including sotrovimab, a neutralising monoclonal antibody (nMAb) and molnupiravir, an antiviral medicine [7]. However, no cure for COVID-19 currently exists and interest in using supplements to counteract COVID-19 symptoms remains high. One study investigated whether spermidine could be used therapeutically against COVID-19 [8]. It found that SARS-CoV2 infection down-regulated cellular autophagy and spermidine levels by interfering with different metabolic pathways. Targeting these pathways with exogenous administration of spermidine and other autophagy-inducing compounds maintained autophagy and reduced viral replication. This shows potential for using an autophagy-inducing compound like spermidine as a treatment for SARS-CoV-2. While not a miraculous cure-all for morbidity and mortality, when taken as part of a healthy diet and lifestyle, spermidine supplements can protect against disease, prolong longevity and may have future applications against COVID-19.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990190/
[2] https://www.science.org/doi/10.1126/science.aan2788
[3] https://pubmed.ncbi.nlm.nih.gov/23022483/
[4] https://academic.oup.com/ajcn/article/108/2/371/5046172
[5] https://ods.od.nih.gov/factsheets/COVID19-HealthProfessional/
[6] https://elifesciences.org/articles/57950
[7] https://www.nhs.uk/conditions/coronavirus-covid-19/treatments-for-coronavirus/
[8] https://www.biorxiv.org/content/10.1101/2020.04.15.997254v1