Friday Hope: Capsaicin: Inhibiting Spike Protein-Induced Line-1 Retrotransposition

This much understudied nutraceutical has profound antioxidant, antitumor and antiamyloid properties as well as the ability to inhibit platelet aggregation.

Capsaicin suppresses L1 retrotransposition. (A) The rationale for L1 retrotransposition assay. L1 with a retrotransposition reporter cassette is expressed under the L1 cognate promoter that is located in the 5′ UTR of pYX014. The L1 retrotransposition reporter is the Firefly luciferase (F. luciferase) gene interrupted by an antisense intron, which has its own promoter (Pro), and is expressed from the antisense strand relative to the L1 promoter. Only after L1 transcription, splicing, reverse transcription of the spliced L1 mRNA, and integration into the host genome, the Firefly luciferase activity is detected. Activity of the Renilla luciferase (R. luciferase) gene is measured as a transfection control. (B,D) Effect of capsaicin (B) or Sho-seiryu-to (D) on cell viability. 293T cells were incubated with capsaicin (B) or Sho-seiryu-to (D) at the indicated concentrations for 3 days. (C,E) The effect of capsaicin (C) or Sho-seiryu-to (E) on L1 retrotransposition. 293T cells were transfected with the L1 retrotransposition reporter construct. Capsaicin (C) or Sho-seiryu-to (E) was added at the indicated concentrations at 24 h post-transfection. Luciferase activity in the cells was evaluated at 4 days post-transfection. Values are expressed as the means + S.E. of at least three independent experiments. * p < 0.05; *** p < 0.005; **** p < 0.001; n.s., no significance. 

Now that we know the Spike Protein is able to hijack Line-1 and retrotranscribe its RNA into our DNA, it is imperative to seek remedies for this phenomenon. Please see my most recent post for details about the Spike and Line-1. In that post I promised to search for natural solutions. Again, Nature does not fail to deliver. In the humble yet pungent chili pepper we find a powerful ally. Capsaicin. This nutraceutical is able to inhibit Line-1 retrotransposition, making it a potentially magnificent therapeutic.  

Though I am quite certain that all reading this know what Capsaicin is, here is offered a brief primer: 

Capsaicin was first isolated in 1816 by Christian Bucholz. Capsaicin is a chili pepper extract, genus Capsicum, with analgesic properties. Its chemical composition was first determined in 1919. They explained the biosynthetic pathway in the 1960s. Since its discovery, it is used as a homeopathic remedy to treat burning pain using the concept of "treating like with like" or counter-irritant. The first reports of its pain-relieving properties appeared in the mid-1850s as a recommendation to use it for parts of the body that burn or itch. Since the first reports, one uses various preparations of capsaicin to treat a variety of chronic painful conditions. Systematic reviews have shown that capsaicin is efficacious in treating a variety of conditions, including: 

Nondiabetic neuropathic pain[1] 

Postherpetic neuralgia[2] 

Osteoarthritis 

Chronic musculoskeletal pain[3] 

Post-mastectomy pain syndrome 

Burning mouth syndrome 

Overactive bladder 

Gastropathy 

Postoperative nausea and vomiting 

Pruritus[4] 

Pruritus ani 

Postoperative sore throat 

Improving cough reflex sensitivity in patients with a history of dysphagia and other swallowing related disorders[5] 

Chemotherapy- and radiotherapy-induced mucositis. 

Capsaicin 
https://www.ncbi.nlm.nih.gov/books/NBK459168/# 

To the above mentioned abilities, we can add several more – especially with regards to the Spike Protein. Let’s first start with Capsaicin’s ability to inhibit Line-1. 

In this study, we found a novel activity of capsaicin, the inhibition of L1 retrotransposition. Since L1 retrotransposition is proposed to be mutagenic and can cause tumorigenesis [9,10], capsaicin may suppress the progression of tumorigenesis through the inhibition of L1-mediated mutagenesis. Collectively, capsaicin possesses several properties that exhibit anti-cancer activities and can therefore be a potent candidate for use in anti-cancer therapies, especially in the case of certain cancers where L1 plays a role in tumorigenesis [9,10]. 

In conclusion, we demonstrated the potential of capsaicin for inhibiting retroviral RT activity and suppressing L1 retrotransposition, possibly via inhibition of RT activity of ORF2p. Our findings suggest the potential of capsaicin for suppressing cancer development and they may facilitate the studies of capsaicin or related compounds, capsaicinoids, for cancer prevention and treatment. 

Inhibition of LINE-1 Retrotransposition by Capsaicin 
https://pmc.ncbi.nlm.nih.gov/articles/PMC6214084/ 

This could prove quite useful in stemming the overwhelming rise in cancer diagnoses. Of course, we need studies to prove this. And, speaking of studies, I am confounded that there are so very, very few studies using Capsaicin, given its abilities, Regarding COVID directly, I can find but a handful. One, very interestingly, shows how Capsaicin can achieve the same results as something one may consider not as safe as Capsaicin: Remdesivir. 

Further studies revealed that molecular docking of RdRp, which is popularly called RNA-dependent RNA polymerase, a key enzyme replication of virus with capsaicin binding at free energy of −7.3 kcal/mol, which is almost similar to remdessivir drug having free energy binding of −9.0 Kcal/mol [247] and a target to search out actual therapeutic agents for COVID-19. Thus, these above studies ascertain that capsaicin alone is a potent enough antiprotease drug to combat SARS-CoV-2 virus replication. 

Biomedical and Antioxidant Potentialities in Chilli: Perspectives and Way Forward 
https://www.mdpi.com/1420-3049/27/19/6380 

One other paper pointed out the, perhaps obvious, observation that those who consume high-capsaicin diets fared far better against SARS-CoV-2. 

The SARS-CoV-2 as we see in the announced numbers of World Health organisation a significant discrepancy is seen in terms of number of infected cases to the total population in each county and by 1 million populations. The number of SARS-CoV-2 infected patients witch was announced at 23.11.2020 by countries in Andorra, Bahrain, Montenegro, Luxembourg, Belgium, Qatar, French Polynesia, Czech Republic, Aruba, Armenia, San Marino, Guam, Palestine, United States of America, Panama, Switzerland, Spain, Kuwait, France, Vatican, Slovenia, Argentina, Puerto Rico, Liechtenstein, Peru, Brazil, Gibraltar, Netherlands, Austria, Georgia, Macedonia and Portugal had more than 25 thousands infected cases per 1 million population and they are not known to have high capsaicin in their diet (nonenamide) is an active component of Chilli peppers, which are plants belonging to the genus Capsicum or it is not a part of their cuisines except China and Republic of Korea, which they have limited infected cases a the spread of infections is low (case per 1 million population) [2].   

Relation between Covid-19 and high capsaicin diets 
https://magnascientiapub.com/journals/msarr/content/relation-between-covid-19-and-high-capsaicin-diets 

If we look closely at Capsaicin, we discover that it can address many Spike-related and induced pathologies. 

ANTIOXIDANT 

Capsaicin has been revealed to inhibit lipid peroxidation in red blood cell membranes as well as in the liver and mitochondria of mice, and it can block the peroxidation of low-density lipoproteins in humans (10,11). In fact, the antioxidant activity of capsaicin exceeds that of vitamin E in some cases (12). The levels of capsaicin in food can alleviate oxidative stress and increase cellular antioxidant capacity by preventing reactive oxygen species from oxidizing glutathione. 

ANTIAMYLOID 

In the APP/PS1 mouse model, capsaicin reduced the formation of amyloid fibrils from amyloid precursor protein. 

INHIBITING PLATELET AGGREGATION 

Capsaicin inhibits platelet aggregation, potentially by altering the fluidity of the platelet membrane. 

Pharmacological activity of capsaicin: Mechanisms and controversies (Review) 
https://www.spandidos-publications.com/10.3892/mmr.2024.13162 

Best of all, Capsaicin is widely available and inexpensive. Not to mention delicious when consumed in foods! Of course, this is medical research and not medical advice. Please check with your Primary Care Provider before using any medication or supplement. I do hope that more COVID/Spike treatment studies are conducted using Capsaicin, the potential to help us is vast.

We are blessed in Vermont with a glorious extension of late Summer/early Fall weather for the next several days. Ideal to take in the beauty of peak Fall foliage. On a related culinary note, those Fall foliage colors are shared by a wide variety of Chili peppers. I plan to enjoy them in a pork tenderloin rubbed with Chili and oven roasted in citrus juices. I wish everyone a deliciously spicy and healthy Fall foliage weekend.