The authors have declared that no competing interests exist.
Most of the patients with inflammatory bowel disease avoid pepper or spicy food, alleging that this condiment causes anal sensation of burning and accelerates intestinal movements. Capsaicin is the main bioactive component of peppers responsible for the pungent flavor that characterizes red peppers. Capsaicin has been related to several biological effects, including decreased body fat, antianti-inflammatory, anticarcinogenic, antioxidant activites and modulator of intestinal motility. These actions mostly are due to its role as an agonist of the transient receptor potential vanilloid 1 (TRPV1), expressed in the mesenteric nervous system and epithelial cells of the colon. Nonetheless, the anti-inflammatory action of capsaicin is also related to its role in activating the peroxisomal proliferator-activated receptor gamma (PPAR-γ). Topical capsaicin formulations are already used for pain management, but oral administration of capsaicin is rare. Here, we discuss the main actions of capsaicin that could interfere with the symptoms and severity of IBD. Although animal experiments suggest a beneficial effect of capsaicin on colitis, clinical studies exploring the potential analgesic and anti-inflammatory of capsaicin on Crohn or Ulcerative Colitis are scarce. We concluded that there is no evidence that capsaicin aggravates IBD symptoms or severity. On the opposite, experimental studies suggest that capsaicin could reduce intestinal inflammation by a mechanism that could involve not only the TRPV1 receptor but also PPAR γ. However, clinical studies are still scarce, and data regarding capsaicin concentrations, routes of administration, and long-term side-effects need to be better understood before its use.
Inflammatory bowel diseases (IBD) comprise two disorders: Crohn's disease (CD) and ulcerative colitis (UC). The inflammatory process seen in UC extends from the rectum continually forward colon, affecting the superficial layers of the mucosa. The inflammation in CD involves all intestinal layer of any part of the gastrointestinal tract, alternating healthy and inflamed tissue in a non-contiguous pattern
The etiology of IBD is not entirely understood yet. It is triggered by genetic and environmental factors that lead to disruption of the intestinal mucosa barrier with bacterial (or bacteria components) translocation, leading to exacerbated immune responses and chronic inflammation
Innate and adaptative immune responses are involved in the development and progression of IBD. The imbalance between regulatory T cells (Treg) and effector T cells (Th1, TH2, and TH17) is related to the development of UC and CD
Pain is a recurrent IBD manifestation, which is present in more than 80% of patients
Pepper, together with foods rich in fiber, is the most cited avoided foods for IBD active and in remission due to the association of such condiment with burning sensation and increased bowel movement
Capsaicin (trans-8-methyl-N-vanillil-6-Nonenamide) and dihydrocapsaicin are the main capsaicinoids from peppers (
Studies in rats showed that the absorption of capsaicin (isolated) occurs mainly in the proximal portion of the gastrointestinal tract. Following intragastric administration, approximately one-third to one half of the capsaicin dose was absorbed from the stomach. The total intestinal absorption amounted to almost 90%
The amount of capsaicin reaching colon to be absorbed is not well known. It is possible that pure capsaicin has a faster and more proximal absorption than capsaicin contained in the spicy foods. It is well known that interactions with other food components such as dietary fibers can slow the absorption rate of some nutrients. In this way, a more significant portion of capsaicin from natural food could reach the colon compared to pure capsaicin. Some individuals allege that capsaicin containing foods induce an anal sensation of burning, suggesting that capsaicin reaches the distal parts of the colon. Nonetheless, studies with healthy individuals receiving capsaicin capsules showed that burning sensation during bowel movements was not related during the experiment
Capsaicin has been related to several biological effects, including reduction of body fat
TRPV1 activation leads to the release by sensory fibers of neuropeptides such as substance P (SP) and the calcitonin gene-related peptide (CGRP). These neuropeptides, besides their vasodilator effects, drive the transmission of nociception in the colonic mucosa. In this way, activation of TRPV1 contributes to the generation of inflammatory responses through the recruitment and migration of leukocytes to the site of inflammation, a process that is accompanied by visceral hypersensitivity
The transient activation of TRPV1 leads to the influx of calcium ions, leading to the membrane depolarization that results in an action potential that propagates the signaling to the brain. However, when a stable and persistent agonist, such as capsaicin, is present, TRPV1 significantly increases the influx of calcium to the intracellular environment of sensitive fibers. Organelles expressing TRPV1 also release calcium into the intracellular environment. The persistently elevated levels of intracellular calcium cause dysfunctionality of nerve fibers due to temporary loss of membrane potential. In this way, chronic capsaicin exposition results in inhibition of pain transmission by inducing persistent calcium influx and nerve fiber dysfunctionality. Capsaicin also downregulates the synthesis, storage, transport, and release of SP and CGRP, both messengers of peripheral pain impulses to the central nervous system (
Some studies have shown that TRPV1 channels are involved in the induction and progression of colitis in humans and experimental models
Utsumi et al. (2018) investigated the contributions of TRPV1 and TRPA1 in a model of sodium dextran sulfate (DSS) induced colitis. They observed that pretreatment with high doses of capsaicin (100 mg/kg), worsened rectal bleeding, and other inflammatory signs of colitis. In agreement, DSS-induced colitis in TRPV1 KO mice was less intense than in wild-type controls, suggesting that TRPV1 is associated for the colitis progression
However, previous studies of Massa and colleagues showed that colitis induced by dinitrobenzene sulfonic acid was aggravated in TRPV1KO mice
Few studies have evaluated the role of TRPV receptors in human colitis. A study comparing colon biopsies of patients with active IBD and healthy controls showed that TRPV1 was increased in IBD patients. TRPV1 was also highly expressed in infiltrating inflammatory cells of patients with active disease. Nonetheless, TRPV1 expression was not associated with the disease severity
The reduction of proinflammatory cytokines, chemokines, and adhesion molecules related to capsaicin activity seem to involve pathways not mediated by TRPV1. Capsaicin is also an agonist of the peroxisome proliferator-activated receptor (PPAR), especially of PPAR-γ
Although there are no specific studies with IBD patients or colitis models, the participation of PPARγ in the capsaicin actions was confirmed by studies with macrophages cell line (RAW) that do not express TRPV1. In this cell line, capsaicin inhibited the lipopolysaccharide (LPS) induced production of pro-inflammatory cytokines (TNF, IL-6, and IL-1β). The mechanism was dependent on PPARγ since a PPARγ agonist intensified the cytokine inhibition, and PPARγ antagonist reverts the inhibition caused by capsaicin
In conclusion, studies suggest that capsaicin containing foods unlikely aggravate the symptoms or the severity of inflammatory bowel diseases. On the opposite, some studies in animal models show promising results with the use of capsaicin in the control of intestinal inflammation by a mechanism that could involve not only the TRPV1 receptor but also PPARγ. However, clinical studies are still scarce, and data regarding capsaicin concentrations, routes of administration, and long-term side-effects need to be better understood before its use.
The authors are fellow of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).