In this post, I’m continuing my series on better aging. (You can find the rest of the articles here: 1, 2, 3, 4, 5, 6.) Chili pepper is a culinary element consumed worldwide, especially in China, Mexico, and Italy. Capsaicin is a biologically active alkaloid found in chili peppers that produce their spicy flavor. The irritation produced by these plants is probably a protective mechanism, evolved to deter animals (like us) from devouring them. But ironically, these compounds may offer certain health benefits when eaten – like on cancer.

Why is this the case? It looks like capsaicin interacts directly with cancer cells to slow down their proliferation. Administrating of high doses of capsaicin to rodents can slow growth of prostate cells by up to 80%. The compound binds to the outer membrane of these malignant cells, triggering chemical changes on the cell surface – tearing apart the membranes. This promising research may ultimately lead to the use of concentrated forms of capsaicin as a novel cancer treatment.

But we don’t have to rely solely on the pharmaceutical route to reap the benefits – just eating them seems to work as well. Epidemiological studies have long shown that consuming spicy foods may improve health and longevity. A Harvard study that assessed the health of almost a half million adults from 10 geographically diverse areas across China found that those who consumed spicy foods six or seven times a week had a 14% lower risk of premature mortality than those who seldom ate it. Hand me the hot sauce, please!

 

Pain relief

Capsaicin has also shown to benefit pain. In fact, Jeff Kindler, the Ex-CEO of the massive drug company Pfizer, has started a company called Centrexion Therapeutics to capitalize on this effect. Their compound CNTX-4975 is an ultrapure, synthetic form of injectable trans-capsaicin that is being evaluated for the treatment of osteoarthritis pain of the knee in humans and canines, as well as in patients with Morton’s neuroma, a painful foot condition. This compound is injected directly into the knee or the foot and selectively targets the capsaicin receptor (also called the vanilloid receptor 1 or the TRPV1 channel) on pain nerve fibers to inactivate them. By the way, these receptors are also highly expressed in the taste buds within the papillae of the tongue.

Inactivating the TRPV1 channels with high enough dose in the knee and foot, however, can result in months of pain relief as those fibers are no longer able to send pain signals to the brain, and the relief is maintained until the nerve fiber regenerates. Knee pain was the biggest issue in the few years before the passing of my 101-year-old grandmother in 2014. It would have been great to have an effective therapy to address it. I hope this pans out in clinical trials.

 

Immunity and autoimmunity

Capsaicin has long been shown to exhibit antimicrobial and antiviral activity. It kills things like Helicobacter pylori, and even Group A streptococci (Streptococcus pyogenes), which is a major human pathogen. This antimicrobial property may have an important effect on the human gut microbiota, but how capsaicin affects its composition and activity need more attention.

Not only is there therapeutic application of capsaicin receptors for pain, but these receptors are also widely expressed in both our innate and adaptive immune cells. Inhibiting these receptors can suppress inflammation. For example, in studies on serious gum infection (periodontitis), the production of inflammatory markers (TNF-α, IL-1β, IL-6, IL-12, and iNOS) was suppressed after capsaicin treatment. Interestingly, a recent study demonstrated that this compound can cause the migration of resident immune cells (microglia) in the brain, which is an important function to clean up brain toxins and waste.

 

Autoimmunity

Autoimmune diseases are characterized by an active immune response against one’s own body. When looking at the distribution of autoimmune diseases and the consumption of capsaicin, living near the equator associates with greater intake of spicy food. Interestingly, living closer to the equator also associates with a lower risk of having an autoimmune disease compared with living near the polar region. In fact, there is an increasing amount of evidence for the emerging role of capsaicin in autoimmune diseases such as rheumatoid arthritis and autoimmune diabetes.

Rheumatoid arthritis is a debilitating disease characterized by inflammation of the joint with subsequent destruction of cartilage. These patients have higher levels of certain pain-related neuropeptides in their synovial fluid, which can drive more blood flow to affected joints. Injecting capsaicin can lower the concentration of these pain peptides and alleviate joint inflammation. Hence, the effective pain modification by the Centrexion Therapeutics’ product.

Type 1 Diabetes Mellitus is an another autoimmune disease. It is caused when our immune system destroys insulin-producing cells of the pancreas (β cells). Our nervous system communicates with the pancreas via nerve fibers that express the capsaicin receptor. Injecting a high dose of capsaicin under the skin of neonatal mice destroys these nerves. In the pancreas, this processes reduces the secretion of pathogenic peptides, prevents inflammation, and prevents the destruction of the β cells. Injecting capsaicin also diminishes aging-associated weight gain and improves the regulation of glucose in rat models of type 2 diabetes. The combined beneficial effect on β-cells preservation, along with weight and glucose control, make capsaicin, and capsaicin-like drugs, a potential target for treating type 1 and type 2 diabetes.  

 

Conclusion

Capsaicin has broad therapeutic potential. It will be interesting to see further research into autoimmunity. However, if you are now more eager to incorporate peppers into your diet, maximize your ability to use these compounds by blending, cutting, and cooking the peppers. Doing so improves the release of capsaicin, while pairing peppers with fat improves absorption since capsaicin is a lipid-soluble compound. 

 

References

1. Joshua Tewksbury & Gary Nabhan. Seed dispersal: Directed deterrence by capsaicin in chilies. Nature, 2001.
2. Akio Mori et al., Capsaicin, a Component of Red Peppers, Inhibits the Growth of Androgen-Independent, p53 Mutant Prostate Cancer Cells. Cancer Res, 2006
3. Jitendriya Swain and Ashok Kumar Mishra. Location, Partitioning Behavior, and Interaction of Capsaicin with Lipid Bilayer Membrane: Study Using Its Intrinsic Fluorescence. J. Phys. Chem. B, 2015,
4. Jun Lv et al. Consumption of spicy foods and total and cause-specific mortality: population based cohort study. BMJ, 2015.
5. ScienceAlert 2015.12.09