Are you a hothead who loves spicy food? If so, researchers from the Chinese Academy of Medical Sciences have some good news for you! Researchers conducted a long term retrospective study from 2004 to 2008 and formed a diverse group (ages 30 to 70) of 512,891 million human subjects in 10 regions in China. Through the data, scientists from this study concluded that those who consumed spicy foods 6 or 7 days a week showed a 14% relative risk reduction in total mortality compared with those who ate spicy foods less than once a week. In other words, individuals who consumed spicy food were shown to live slightly longer on average! This is amazing news, but before we explore the health claims of spicy food, let us briefly discuss the cultural context of spicy food including peppers and chiles.
Throughout history, spices have played an integral role in many cultures and have also significantly impacted the world in which we live in today. From garlic to the mustard seed, almost every spice was utilized for one reason or another. Perhaps the most obvious reason is flavor or coloring, but spices were also used for preservation long before proper storage techniques for food were established. Around the 1500s, with the discovery of the New World, peppers emerged as the most popular spice. Old World spices included the Szechuan pepper, a bitter leaf bud with many anesthetic properties. On the other hand, In South America – the New World – Andean chiles were discovered, which were later measured to have a Scovile heat rating of over 250,000 units! Talk about spicy! Keep in mind that a Jalapeno pepper only has a Scovile heat rating of around 3,500 units. It was these former types of chiles, the south American chiles, which led to the emergence of spicy food as we know it today: pungent, yet not numbing like Old Word Spices. For example, contrast the heat you get from a Habanero pepper with the heat you get from wasabi. When we think “spicy”, we typically think of heat similar to that from a habanero: we typically think of chillies! So what compound in chiles gives contemporary spicy food its health benefits? The literature points towards capsaicin, a critical bioactive constituent found in almost all chili peppers. Capsaicin is thought to be the key molecule that explains the profound medicinal effects attributed to spicy foods. This essay will examine four health benefits of capsaicin: First we will look at how capsaicin can help promote weight loss. Then we will look at how capsaicin can reduce the risk of diabetes. Following this, we will examine how capsaicin can lower the risk of other autoimmune diseases such as arthritis. Finally, we will examine the antimicrobial properties of capsaicin.
Effect of Capsaicin on Metabolism and Energy Expenditure
The effects that capsaicin has on the metabolic pathways in rodents is well established: energy expenditure increases, lipids become preferentially oxidized for energy, and loss of appetite. However, recreating these ideal results in humans has been more difficult; oftentimes studies arrive at contradictory or inconsistent conclusions. In addition to capsaicin’s stimulation of the beta-2-adrenergic receptor to increase fat oxidation, CAPS also upregulates uncoupling protein 1 (UCP1), a key molecule in brown adipose tissue (BAT) thermogenesis – thus explaining the increased energy expenditure (Yoneshiro et al., 2012). Until recently, BAT, a primary source for thermogenesis, was believed to be absent in humans; now it is known that metabolically active BAT in humans varies from person to person. In one study, for example, BAT could be detected in 55% of participants in their 20s had BAT, but only 10% of participants in their 60s (Saito and Yoneshiro, 2013). The recent discovery of BAT and its effects on thermogenesis can partially explain why the results of capsaicin on fat oxidation in humans are slightly inconsistent.
However, this study demonstrates that the energy expenditure effects of capsaicin are intensified by the presence of BAT (Yoneshiro et al., 2012).These findings suggest that “capsaicin [and capsinoids] are effective in people with BAT but not in those without active BAT” (Yoneshiro et al., 2012). This recent finding could limit the potential uses of capsaicin, since BAT is lowest in the obese and elderly. Regardless, in those who do have adequate brown adipose tissue, capsaicin can increased thermogenesis by 5 to 20%.
The idea that capsaicin shifts substrate oxidation from carbohydrates to fats in humans is also controversial and in need of future research. In a recent study, 10 mg capsaicin was administered to participants, and measuring the resting exchange ratio of participants, it was found that capsaicin increased lipid oxidation (Josse et al., 2010). However, another study determined that substrate oxidation was no different amongst participants given a spicy meal, and a control (Smeets and Westerterp-Plantenga, 2009). Interestingly, neither of these studies mention nor control for BAT. Therefore, further research needs to be done which controls for this variable, in order to more clearly establish the true effects capsaicin has on substrate oxidation. Regardless of which substrate is ultimately oxidized, the effects are clear nonetheless: thermogenesis increases dramatically (up to 20%), resulting in a faster metabolism, which in turn results in a higher total daily energy expenditure (TDEE) for weight loss.
Antiglycative effects of capsaicin on Diabetes
Capsaicin consumption has also been found to play a key role in reducing the levels of advanced glycation end products formed within our bodies during protein glycation. Glycation essentially involves a series of reactions between sugars and amino acids that is cut up into three stages; an early stage producing Amadori products, a middle stage where dicarbonyl MG modifies proteins, and a late stage involving protein crosslinking (Hsai et al., 2016). The final byproduct of protein glycation is the formation of advanced glycation endproducts or AGEs.The full molecular mechanism underlying pathogenesis of glycation is not fully characterized however but has been linked to stimulating reactive oxygen species and inflammatory mediator production causing diseases. Higher physiological levels of AGE’s in our bodies have also been found to be detrimental as they are linked to decreased insulin sensitivity which increases the risk of type 2 diabetes (de Courten et al., 2016). This process occurs when AGE’s bind to their receptor RAGE, and once fully accumulated, the AGE’s will stimulate the RAGE receptor to induce production of reactive oxygen species and inflammatory cytokines which in turn causes activation of disease-associated physiological signalling in the body (Ott et al., 2014). The soluble form of the RAGE receptor (sRAGE) has also been found to have higher levels in serum in nondiabetic rats, and administration of sRAGE can improve symptoms such as inflammation in hyperglycemic rats (Kang et al., 2011).
Capsaicin however has been found to have a significant inhibitory effect on protein modification of the middle stage of glycation and inhibiting protein cross linking in the late stage while also restoring sRAGE levels in previously diabetic rats.. While employing a BSA-MG assay alongside a SDS-PAGE to visualise degrees of protein modification, it was found that introduction of CAPS during a nine day glycation period by dicarbonyl MG reduced the loss of BSA alongside forming a high molecular weight protein which indicated that CAPS played a protective role in crosslinking (Hsai et al., 2016). The figure to the right shows the effect on normal rats (Group N) versus hyperglycemic rats (Group D).
AGEs accumulation and RAGE expression in the kidneys of experimental diabetic rats are inhibited by CAPS. (Hsai 2016)
Continuous administration of CAPS for 12 weeks also aided in restoring the kidney sRAGE levels in hyperglycaemic rats however the underlying mechanism is also relatively unknown and might be associated with regulation of ADAM10, a disintegrin and metalloprotease. Figure B shown below illustrates the lack of effect CAPS plays in normal rats while greatly increasing sRAGE levels in hyperglycemic rats.
By providing a protective effect against crosslinking, capsaicin can inhibit this linkage and diabetes as a whole. Again, I stress that future studies in this area of research are needed, since Kang’s 2011 study looked at the effects of inhibiting cross linking in rats. Therefore, a future study which administers capsaicin to diabetic human patients would be helpful.
The effect of capsaicin on autoimmune diseases
To understand the influence of capsaicin on autoimmune diseases, one must first understand the role it plays on the body’s immune system. Upon discovery of the bioactive agent capsaicin, scientists soon discovered its main target receptor, transient receptor potential vanilloid subfamily member 1 (TRPV1) receptors. TRPV1 receptor was originally known to be detectors of pain and heat, but recent studies also found that TRPV1 receptors could cause anti-inflammatory diseases—stimulation of TRPV1 signals the release of neuropeptides into the blood, which notify the body of possible signs of inflammation (Devesa et al., 2011). To prevent overly expressed inflammatory responses, capsaicin acts as a TRPV1 agonist that desensitize or inhibit hyperactive TRPV1-expressing sensory nerves (Deng et al., 2016). Inhibition of these receptors regulate T cell activation and effector cytokines production by suppressing tumor necrosis factor, interleukin-2 and interferon-γ release (Majhi et al., 2015). This eventually lowers the occurrence of cell apoptosis and autoimmune activities such as inflammation and increased body temperature. What does this mean? Capsaicin can modulate, or reduce, a hyperactive immune system by inhibiting TRPV1. This causes the immune system to stop attacking “self” components, as the immune system is designed to attack foreign components. This results in a cessation of autoimmune activity, and ultimately, this phenomena can result in relief from pain, which is why capsaicin is often classified as an analgesic. On the other hand, capsaicin promotes the immune system when we truly need it, such as when we get sick: capsaicin was also found to upregulate the phosphorylation of nuclear factor Kappa B, a signaling molecule used in immune responses. Therefore, capsaicin could also promote a robust immune response for nonautoimmune diseases (Liu et al., 2015).
Antimicrobial Effects of Capsaicin
Finally, this essay is going to investigate the health claim that capsaicin kills bacteria and other pathogens which make us sick. One of the most problematic bacteria which infect us is Streptococcus pyogenes, which can be responsible for sore throat and fever. However, this bacteria is highly resistant to antibiotics such as erythromycin. This results in the emergence of deadly bacteria strains; you might have heard of Streptococcus’s deadly, resistant cousin, MRSA. However, capsaicin provides a promising means of destroying these resistant bacteria. A 2015 study treated 32 isolates of Streptococcus pyogenes (of which 27 were antibiotic resistant) with capsaicin. This study aimed to determine if capsaicin was a bactericidal agent, and if so, what the minimum effective dose would be. All 32 strains were killed with capsaicin treatment, with some requiring as little as 64 ug/mL capsaicin. Therefore, CAPS has been shown to be a very potent bactericidal agent. Another benefit, which is also highly important, is that no strains were found to develop resistance to capsaicin. Therefore, this compound may provide an answer to the contemporary controversy surrounding prescription of antibiotics. Additionally, in all 32 strains, biofilm production decreased, up to 97%. Biofilms, a “slime” produced by bacteria on inorganic surfaces (ie: prostheses, artificial valves) can dramatically reduce a patient’s outlook. Antibiotics do not readily penetrate biofilms; therefore, biofilms can result in chronic bacterial infections which are difficult to clear. Capsaicin reduced biofilm production, and therefore could be used to improve the outlook of patients suffering from chronic bacterial infections. A final benefit of capsaicin which the study discovered is that it reduced the virulence of Streptococcus pyogenes. Virulence refers to how severe a bacterial infection will be. This study examined two markers of virulence: hemolytic activity and extent of intracellular invasion. With the minimum level of capsaicin, a 1000-fold reduction in intracellular invasion was observed. The control, which was not treated with any antibiotics nor capsaicin, was found to have a 75% rate of hemolysis. This means that 3 of every 4 red blood cells in the agar medium were damaged and metabolized by Streptococcus pyogenes. On the other hand, strains exposed to as little as 8 ug/mL capsaicin had a 10% rate of hemolysis. Therefore, at the least, capsaicin was responsible for a seven-fold reduction of hemolysis. Again, these findings support the claim that capsaicin can be used to improve outlook of patients infected with bacteria (Marini et al. 2015).
So how exactly does capsaicin kill bacteria? Future research is needed to completely elucidate this mechanism, but the above study put forth a hypothesis that the compound attacks the membrane by poking holes into it, in a similar fashion to the complement system of our own immune system. Interestingly enough, this is the same mechanism used by other foods with antimicrobial benefits, such as oregano or thyme – which have the active ingredient known as carvacrol. Either way, once the membrane has been perforated, the extracellular fluids rush into the pathogenic cell by osmosis, causing lysis of the pathogen. The study also produced a hypothesis for capsaicin’s protective effect against biofilms. The study suggests that capsaicin lowers capability for adhesion, which prevents the biofilm from sticking to an inorganic substance in the body. Since a biofilm can only form on an inorganic surface, preventing the adhesion therefore prevents the biofilm. Even though the mechanisms may not be fully known, the end results are quite clear: capsaicin can fight off infections by directly killing pathogenic bacteria, preventing biofilm formation, reducing bacterial hemolysis, and reducing intracellular infectivity (Marini et al. 2015). Talk about a power food!
After examination of the four main roles of capsaicin on the human body, we have a clear understanding of the benefits of spicy foods. However, further research is always helpful, so here are some future issues to be explored. One possible application of future research is to enhance the effectiveness of capsaicin for weight loss on individuals who are at higher risks for health complications. Another step to be taken in research of capsaicin is establishment of studies which control for all external variables. We noticed that a majority of studies evaluating the change in energy expenditure due to capsaicin did not control for the effects of brown adipose tissue. Despite these drawbacks, the beneficial effect of capsaicin should still be considered. In addition to its role against autoimmune diseases and its antiglycative effects, capsaicin is also thought to promote increased blood circulation, and it is thought to protect against UV radiation. Studying this latter area of interest in specific – capsaicin’s protection against UV radiation – could one day lead to a preventive treatment against cancer. However, further research is still needed in order to evaluate these effects in humans, and new research may also be conducted to find other potential receptors for capsaicin. Lastly, research and development of capsaicin analogues (capsinoids) is underway to mitigate negative side effects such as pungent odor and taste. But as with all studies involving analogues for metabolites, it is a long and arduous process requiring FDA approval. So for the time being, if you want to reap the health benefits of capsaicin, there is no better option than spicy food. Hotheads rejoice!
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