Cayenne

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Capsicum spp.

Capsicum annuum L. var. annuum; C. annuum L. var. glabriusculum (Dunal) Heiser & Pickersgill [syn. C. frutescens L.]; C. baccatum L.; C. chinense Jacq.

[Fam. Solanaceae]

Overview

Cayenne is marketed in the U.S. as a food, spice, and dietary supplement (in tablets, capsules, and occasionally, as a tincture). Common names for cayenne include cayenne pepper, chili pepper, paprika, red pepper, tabasco pepper, bird pepper, African bird pepper, piquin, aji pepper, Brown’s pepper, Peruvian pepper, piris, habañero pepper, and bonnet pepper. Cayenne is one of the fastest growing botanical imports, accounting for approximately 12% of the total annual value of U.S. spice imports. New Mexico alone produces approximately 100 million pounds of dried peppers annually (Buzzanell and Gray, 1999). Twenty-three percent of natural food store consumers purchased cayenne at least once during the first half of 1999 (Richman and Witkowski, 1999). Preparations made from the oleoresin in cayenne and oleoresin’s isolated constituent, capsaicin, are used in topical, over-the-counter (OTC) drug products. Capsicum oleoresin topical analgesic lotions and creams, containing the pure compound capsaicin, are available OTC in three strengths, 0.025%, 0.075%, and 0.25% (Palevitch and Craker, 1995; Rosenstein, 1999) for the following uses: inflammation and pain due to shingles, postherpetic neuralgia, rheumatoid arthritis, osteoarthritis, diabetic neuropathy, and post-surgical pain. Other uses for these lotions and creams that are not specified on the labels are to relieve pain associated with psoriasis, chronic neuralgia unresponsive to other forms of therapy, and intractable pruritus (Turkoski et al., 1998).

Description

Cayenne preparations consist of the dried, ripe fruit, usually removed from the calyx, of various capsaicin-rich Capsicum species, such as C. annuum L. [Fam. Solanaceae], including a large number of varieties (Blumenthal, et al., 2000). In Germany, pharmacopeial grade cayenne must contain no less than 0.4% total capsaicinoids, as determined by liquid chromatography (DAB, 1999). [Note: This herb was described under the monograph heading “Paprika (Cayenne)” in the German Commission E monographs (Blumenthal et al., 1998).]

Primary Uses

External

Capsaicin preparations

Neuralgia

Significant reduction of postherpetic neuralgia (Watson et al., 1993; Peikert et al., 1991; Bernstein et al., 1989)

Neuropathy

Improved pain relief for diabetic neuropathy (Capsaicin Study Group, 1991, 1992; Chad et al., 1990)

Psoriasis

Improvement in global evaluation, pruritus relief and combined psoriasis severity scores (Krogstad et al., 1999; Ellis et al., 1993)

Osteoarthritis

Significant reduction in pain and joint tenderness (Altman et al.,1994; Schnitzer et al., 1994; Weisman et al., 1994; McCarthy and McCarty, 1992; Deal et al., 1991)

Other Potential Uses

Internal

Cayenne preparations

Gastrointestinal

Cytoprotective effect (Yeoh et al., 1995)

Peptic ulcer, prevention (Kang et al., 1995; Yeoh et al., 1995)

External

Capsaicin preparations

Fibromyalgia (McCarty et al., 1994)

Cluster headache (Marks et al., 1993)

Chronic rhinopathy (Eberle and Gluck, 1994)

Dosage

Internal

Crude Preparations

Dried fruit: 30–120 mg, 3 times daily, (BHP, 1983). As a digestive aid, 120–450 mg, 2–3 times daily with meals (McKenna et al., 1998). In a clinical study, 10 g powdered fruit was administered one time with meals to stimulate carbohydrate oxidation (Lim et al., 1997). However, this dose is probably too high for regular consumption.

Infusion: 240 ml boiling water is poured over 0.5–1.0 teaspoon of cayenne and steeped for 10 minutes; 1 tablespoon is drunk, diluted with hot water when needed (Hoffmann, 1992; Lust, 1974).

Tincture: 1:20 (g/ml), 60% ethanol: 0.3–1.0 ml, 3 times daily, or when needed (Boon and Smith, 1999; BPC, 1968; Hoffmann, 1992; Karnick, 1994).

Standardized Preparations

Oleoresin: 1.2 mg (maximum dose) (MD), 1.8 mg (maximum daily dose) (MDD) (GSL, 1984–1994).

External

Crude Preparations

Liniment: Hot oil emulsion containing dried cayenne powder or alcoholic tincture is applied locally by friction method (Blumenthal et al., 2000).

Standardized Preparations

Ointment or cream: Semiliquid preparation containing 0.02–0.05% capsaicinoids in an emulsion base, is applied to affected area (Blumenthal et al., 2000).

Oleoresin: 2.5% maximum strength (GSL, 1984–1994 from Newall et al., 1996) is applied locally.

Poultice: Semisolid paste or plaster which, when applied locally, produces 10–40 mcg capsaicinoids per cm² (Blumenthal et al., 2000).

Tincture: 1:10 (g/ml), 90% ethanol, aqueous-alcoholic preparation containing 0.005–0.01% capsaicinoids, is applied locally (Blumenthal et al., 2000).

Pure Capsaicin Preparations

For diabetic neuropathy, 0.075% capsaicin cream or ointment is applied 4 times daily. For postherpetic neuralgia, 0.025%
capsaicin cream or ointment is applied 4 times daily (Boon and Smith, 1999; Pizzorno and Murray, 1999).

Duration of Administration

External

Crude Preparations

Commission E recommends no longer than two days; 14 days must pass before a new application can be used in the same location. Longer use on the same area may cause damage to sensitive nerves (Blumenthal et al., 1998).

Preparations Containing Pure Capsaicin

Three to four applications daily for 2–6 weeks may be required (Kruse and Eland, 1999).

Warning: Preparations made from cayenne irritate the mucous membranes even in very low concentrations and cause a painful burning sensation. Patients should avoid the contact of cayenne preparations with mucous membranes, especially the eyes (Blumenthal et al., 1998).

Chemistry

Cayenne contains up to 1.5% pungent principles known as capsaicinoids (usually 0.1–1.0%), composed of 49–69% capsaicin, 22–36% dihydrocapsaicin, 7.0–7.4% nordihydrocapsaicin, 1–2% homodihydrocapsaicin, and 1–2% homocapsaicin (Bennet and Kirby, 1968; Duke, 1985; Wood, 1987). Other constituents of cayenne include carotenoids and ascorbic acid (vitamin C) (Bruneton, 1999).

Pharmacological Actions

Internal

Human

Crude Preparations

Dried powder can protect against aspirin-induced gastroduodenal mucosal injury when taken 1/2 hour prior to aspirin (Brinker, 2001; Yeoh et al., 1995); protects against peptic ulcer (Kang et al., 1995); increases fibrinolytic activity (Visudhiphan et al., 1982); stimulates carbohydrate oxidation (Lim et al., 1997); gastrointestinal stimulant (Osol and Farrar, 1955).

Animal

Antigenotoxic and anticarcinogenic (Surh et al., 1998).

External

Crude Preparations

Local hyperemic and local nerve-damaging activity (Blumenthal et al., 1998); rubefacient and vasostimulant (BHP, 1996; Kapoor, 1990). Capsicum oleoresin does not uniformly induce neuropeptide activity as reliably as purified capsaicin. Clinical efficacy studies have shown purified capsaicin depletes the neuropeptide-active agent substance P, which is stored in sensory neurons, though no similar studies have been done on capsicum oleoresin. Capsascin also further blocks resynthesis of substance P (Cordell and Araujo, 1993).

Pure Capsaicin Preparations

Block pain neurotransmitter, substance P (Ellison et al., 1997); dilate blood vessels, release histamine and reduce perfusion in lesional skin (Krogstad et al., 1999); reduce and relieve pain; cause activation followed by desensitization of the sensory neurons on short- and long-term treatments (Ellison et al., 1997; Munn et al., 1997; Vickers et al., 1998).

Mechanism of Action

Internal

Intragastric capsaicin stimulates afferent nerve endings in animal tests, suggesting that its gastroprotective effects may be caused by increased mucosal blood flow rather than by prostaglandin production (Yeoh et al., 1995).

Cayenne affects the cardiovascular system, reducing trigylceride levels and platelet aggregation, and increasing fibrinolytic activity (Pizzorno and Murray, 1999).

Reduces serum triglyceride levels without an alteration in serum cholesterol or pre--lipoproteins, and stimulates lipid mobilization from adipose tissue (Boon and Smith, 1999).

Increases catecholamine (plasma epinephrine and norepinephrine concentration) levels (Barna and Sreter, 1986; Lim et al., 1997).

Inhibits lipid peroxidation and myeloperoxidase activity in ethanol-induced gastric mucosal lesions; thereby demonstrating gastroprotective activity, which may be useful in chemoprevention (Park et al., 2000).

Vanilloid (capsaicin) receptors act in nonspecific manner (not specifically as previously believed) to activate sensory neurons. Capsaicin and the protons lower the heat threshold of the receptor, while it is the heat (<48°C) that opens the channel pore of the vanilloid receptor neurons (Szallasi and Blumberg, 1999).

External

Capsaicin Preparations

Activate nociceptive fibers, which induces the release of excitatory neurotransmitters (substance P, N-methyl-D-asparic acid), bind to specific vanilloid (capsaicin) receptors, and its effects are reversible (Szallasi and Blumberg, 1999; Fusco and Giacovazzo, 1997; Lotz, 1994).

Induce a selective analgesic effect by depleting substance P, a neuropeptide of 11 amino acids that mediates the transmission and modulation of pain impulses from the peripheral nerves to the spinal column. Capsaicin initially stimulates substance P release from peripheral sensory, C-type nerve fibers, then prevents its reuptake, and also blocks its transport within the neuron, which causes its eventual depletion, resulting in analgesia. The depletion of substance P initially takes one to three days, though with continued use the analgesic effect may last for weeks (Boon and Smith, 1999; Fusco and Giacovazzo, 1997; Tyler, 1992).

Contraindications

Internal

Crude Preparations

Inhalation is contraindicated due to immediate bronchoconstriction caused by capsaicin (Fuller et al., 1985). Ingestion is contraindicated in cases of chronic irritable bowel due to neural irritant and intestinal contraction properties of capsaicin (Buck and Burks, 1986), gastroduodenal ulcers, acute gastritis, pulmonary tuberculosis, and hemorrhoids (But et al., 1997). However, a randomized, comparison clinical study did not find gastric mucosal damage in patients with duodenal ulcers who consumed cayenne (Kumar et al., 1984).

External

Cayenne preparations are contraindicated for application on injured skin, allergies to cayenne preparations (Blumenthal et al., 1998), or use near the eyes (Brinker, 2001).

Pregnancy and Lactation: No known restrictions (McGuffin et al., 1997).

Adverse Effects

Commission E noted that in rare cases, a hypersensitivity reaction (urticaria) can occur (Blumenthal et al., 1998). Capsaicinoids are strongly irritating to mucosal membranes and inhalation of cayenne can produce a form of allergic alveolitis.

Drug Interactions

External

Commission E reported no drug interactions are known, but included the following note: “No additional heat application” (Blumenthal et al., 1998). Angiotensin-converting enzyme (ACE) inhibitors can predispose patients to coughing with application of topical preparations containing capsaicin according to human case reports (Brinker, 2001).

Internal

Crude herb: Capsicum may interfere with monoamine oxidase inhibitors (MAOIs) and antihypertensive therapy (increased catecholamine secretion), and may increase the hepatic metabolism of drugs (glucose-6-phosphate dehydrogenase and adipose lipoprotein lipase activity elevated) (Newall et al., 1996). In an animal study (rabbits), theophylline absorption was enhanced when administered before or simultaneously with cayenne (Bouraoui et al., 1988).

American Herbal Products Association (AHPA) Safety Rating

Class 2d: External: Contraindicated on injured skin or near eyes.

Class 1: Internal: Can be safely consumed when used appropriately. Note: Excessive doses may cause gastrointestinal irritation in sensitive individuals (McGuffin et al., 1997).

Regulatory Status

Austria: Official in the Austrian Pharmacopoeia, ÖAB 1991 (Wichtl, 1997).

Canada: Topical liniments, lotions, and plasters containing capsicum oleoresin or purified capsaicin are schedule OTC (over-the-counter) drugs requiring pre-market authorization and assignment of a Drug Identification Number (DIN) (Health Canada, 2001).

France: Topical preparations are approved for relieving minor articular pain in French Pharmacopoeia, Ph.Fr. X (Bradley, 1992; Reynolds et al., 1993).

Germany: Topical preparations are approved nonprescription drugs of the Commission E monographs (Blumenthal et al., 1998). Dried ripe fruit is official in the German Pharmacopoeia (DAB, 1999). Dried ripe fruit for preparation of hydro-alcoholic mother tincture and liquid dilutions is an official drug of the German Homoeopathic Pharmacopoeia (GHP, 1993).

Italy: Official in Italian Pharmacopoeia (Newall et al., 1996).

Japan: Dried fruit and powdered dried fruit are both official in the Pharmacopoeia of Japan (JSHM, 1993).

Sweden:  Topical capsaicin cream is an approved non-prescription drug (MPA, 1997). No capsicum products are listed in the Medical Products Agency (MPA) “Authorized Natural Remedies” (MPA, 2001).

Switzerland: Official in Swiss Pharmacopoeia, Ph.Helv.VII (Wichtl, 1997). External-use plasters containing cayenne and cayenne extract are nonprescription drugs, with sale limited to pharmacies and drugstores (Morant and Ruppanner, 2001).

U.K.: Capsicum oleoresin and water-soluble capsicum oleoresin are herbal medicines specified in the General Sale List, Schedule 1 (medicinal products requiring a full product license), Table B (external use only) (GSL, 1995).

U.S.: Generally recognized as safe (GRAS) (US FDA, 1998). Dietary supplement (USC, 1994). Capsicum oleoresin and purified capsaicin are safe and effective for use as OTC external analgesics (US FDA, 1979; US FDA, 1983).

Clinical Review

A total of 26 clinical trials conducted on cayenne and capsaicin are summarized in the following tables, “Clinical Studies on Cayenne” and “Clinical Studies on Capsaicin Preparations.” All but one of these studies (López-Carrillo et al., 1994), demonstrated positive effects for indications including gastrointestinal and metabolic conditions. Five studies investigated gastrointestinal effects related to the regular dietary intake of cayenne powder vs. non-ingestion of cayenne including a protective effect against peptic ulcer (Kang et al., 1995), a gastroprotective effect following ingestion of aspirin (Yeoh et al., 1995), risk of gastric cancer (Lopez-Carrillo et al., 1994), gastric or duodenal mucosal damage (Graham et al., 1988; Kumar et al., 1984), and elevated metabolic rate (Henry and Emery, 1986). A hematology study found significantly higher fibrinolytic activity in Thai subjects who consumed cayenne regulary, compared with American subjects (Visudhiphan et al., 1982).

Table 2, “Clinical Studies on Capsaicin Preparations,” summarizes 18 studies involving a total of 1,326 participants, evaluating the external use of preparations containing pure capsaicin. All but one of the studies (Low et al., 1995) demonstrated positive effects for indications including neuralgia, neuropathy, psoriasis, arthritis, and fibromyalgia. The table includes 14 double-blind, placebo-controlled (DB, PC) studies involving a total of 1,036 participants. Two DB, PC studies investigated topical capsaicin in painful diabetic neuropathy, with statistically significant results related to pain status (Capsaicin Study Group, 1992; Chad et al., 1990). Osteoarthritis was the subject of four DB, PC studies, all with statistically significant results confirming capsaicin’s efficacy in pain reduction (Altman et al., 1994; Deal et al., 1991; McCarthy and McCarty, 1992; Schnitzer et al., 1994). Three DB, PC studies focused on the treatment of rheumatoid arthritis, with two studies reporting significant reduction in pain (Deal et al., 1991; Weisman et al., 1994). One study reported a significant reduction in primary osteoarthritis pain, but no significant reduction in rheumatoid arthritis pain (McCarthy and McCarty, 1992). Other topics investigated with topical capsaicin in DB, PC studies include notalgia paresthetica (Wallengren and Klinker, 1995), fibromyalgia (McCarty et al., 1994), psoriasis (Ellis et al., 1993), and postherpetic neuralgia (Watson et al., 1993). Only one study did not demonstrate a trend in favor of treatment with capsaicin. This was a 12-week, DB, PC study investigating chronic distal painful polyneuropathy (Low et al., 1995). Creams containing low concentrations (0.025–0.075%) of capsaicin have been shown in clinical trials to be effective in the treatment of postherpetic neuralgia (Bernstein et al., 1987; Bernstein et al., 1989; Menke and Heins, 1999; Peikert et al., 1991; Watson et al., 1988; Watson et al., 1993), diabetic neuropathy (Basha and Whitehouse, 1991; Tandan et al., 1992), and other pain syndromes, including cluster headache (Marks et al., 1993).

Branded Products

Axsain^®: GenDerm Corporation / 4343 East Camelback Road / Phoenix, Arizona 85012 / U.S.A. Cream product with 0.075% capsaicin. This product is no longer available.

Capsig^®: Schering-Plough / 2000 Galloping Hill Road / Kenilworth, NJ 07033 / U.S.A. / Tel: (908) 298-4000 / www.sch-plough.com. Cream with 0.025% capsaicin. This product is no longer available.

Chili powder (no product name specified): KNP Trading Pte Ltd, 50 Senoko Drive / Singapore 758 232 / Tel: 65-257 6916 / Fax: 65-753 6916 / www.knp-housebrand.com. Chili powder containing 478 ppm capsaicin.

Saemaul Kongjang 1: No product information available.

Zostrix^®-HP: GenDerm Corporation. Cream product with 0.075% capsaicin.

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