1. Introduction
Capsaicin is a vanilloid alkaloid produced by species of the genus Capsicum, most notably Capsicum chinense, Capsicum frutescens, and Capsicum annuum. As the primary pungent compound in chili peppers, capsaicin belongs to a broader group of metabolites known as capsaicinoids. These compounds interact with sensory neurons in mammals via the TRPV1 (transient receptor potential vanilloid 1) receptor, producing a sensation of heat or burning. While initially an ecological defense mechanism, capsaicin has been increasingly exploited for its therapeutic and metabolic properties, as well as its cultural and culinary value.
2. Molecular Structure and Properties
Capsaicin (C₁₈H₂₇NO₃) comprises a vanillyl aromatic ring, an amide group, and a hydrophobic alkyl chain. Its molecular structure enables both membrane permeability and specific binding to the TRPV1 receptor. Minor structural differences among capsaicinoids — such as the length and saturation of the fatty acid tail — account for variability in pungency and volatility.
Figure 1. Molecular structure of capsaicin:
3. Biosynthesis in Capsicum Species
Capsaicinoids are synthesized in the placental tissues of the fruit via the condensation of vanillylamine (derived from the phenylpropanoid pathway) and a branched-chain fatty acid produced from valine or leucine. Key enzymes include capsaicin synthase (CS), putative acyltransferases (Pun1), and aminotransferases. The genetic regulation of capsaicinoid synthesis varies across cultivars and is influenced by environmental factors such as temperature, nitrogen availability, and stress.
4. TRPV1 Receptor Activation
Capsaicin activates TRPV1, a non-selective cation channel located on nociceptive neurons. Binding of capsaicin lowers the activation threshold of TRPV1, allowing calcium influx and depolarization. This induces pain, heat, and neurogenic inflammation. Prolonged or repeated exposure desensitizes the receptor, leading to defunctionalization and analgesic effects — the pharmacological basis for topical capsaicin use.
5. Capsaicinoid Concentration in Pepper Cultivars
Capsaicinoid levels vary widely between cultivars. Representative examples:
| Cultivar | Species | Scoville Heat Units (SHU) |
| Carolina Reaper | C. chinense | 1,400,000–2,200,000 |
| Trinidad Moruga Scorpion | C. chinense | 1,200,000–2,000,000 |
| Bhut Jolokia (Ghost Pepper) | C. chinense | 800,000–1,041,427 |
| Red Savina Habanero | C. chinense | 350,000–577,000 |
| Tabasco | C. frutescens | 30,000–50,000 |
| Jalapeño | C. annuum | 2,500–8,000 |
| Bell Pepper | C. annuum | 0 |
6. Medical and Pharmacological Applications
Capsaicin is approved for use in topical formulations to treat peripheral neuropathy, osteoarthritis, and postherpetic neuralgia. High-concentration patches (8% capsaicin) have been shown to produce sustained pain relief via cutaneous nerve fiber degeneration. It also demonstrates efficacy in weight loss by increasing thermogenesis, suppressing appetite, and enhancing lipid oxidation. Emerging studies show anticancer effects through mitochondrial depolarization and apoptotic signaling in tumor cells.
7. Ecological and Evolutionary Significance
Capsaicin likely evolved as a deterrent against mammalian seed predators, while remaining palatable to birds, which lack TRPV1 sensitivity and aid in seed dispersal. Its antifungal and antibacterial activity also enhances fruit longevity. Domestication has modulated these traits for culinary and commercial purposes.
8. Risks and Toxicity
High oral doses of capsaicin may cause gastrointestinal irritation, vomiting, and in rare cases, toxicity. Topical overuse can damage sensory nerve endings. Regulatory agencies caution against high-concentration supplements or extracts without medical supervision.
9. Emerging Research and Delivery Systems
Novel delivery technologies including liposomal and nanoparticle encapsulation are improving capsaicin’s bioavailability and targeting. Mild analogs like capsinoids (e.g., capsiate) activate TRPV1 without oral pungency, offering therapeutic alternatives. Research continues into capsaicin’s immunomodulatory and antitumor effects.