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Capsicum Peppers

Scientific Name(s): Capsicum annuum L., Capsicum frutescens L.
Common Name(s): African chilies, Bell pepper, Capsicum, Cayenne pepper, Chile, Chili, Chilli, Chilli pepper, Green pepper, Jalapeno, Louisiana long pepper, Mexican chilies, Paprika, Pimiento, Red, Sweet peppers, Tabasco pepper, Thai peppers

Clinical Overview

Use

Many varieties are eaten as vegetables, condiments, and spices. The component capsaicin is an irritant and analgesic used in self-defense sprays, and in a variety of conditions associated with pain. Other studies have evaluated a role in weight loss, GI conditions, postoperative nausea, and rhinitis, although limited information for these uses is available.

Dosing

For external uses, capsaicin and capsicum creams are available in several strengths, from 0.025% to 0.075% capsaicin. Clinical trials are lacking to guide dosage for other uses.

Contraindications

Topical capsaicin should not be applied to the face or injured skin.

Pregnancy/Lactation

Generally recognized as safe (GRAS) when used as food. Safety and efficacy for dosages above those in foods are unproven and should be avoided. Studies in animals have shown both positive and negative effects.

Interactions

See Drug Interactions section.

Adverse Reactions

Topical, mucosal, and GI irritations are common. Allergies and cross-sensitization to other allergens have been reported.

Toxicology

Toxicity is evidenced in animal experiments in higher dosages. Controversy exists regarding capsaicin's mutagenicity and tumorigenicity. Toxicity from long-term exposure to chili powder has not been found, and the use of defense sprays likewise has not resulted in reports of toxicity.

Scientific Family

  • Solanaceae

Botany

The genus Capsicum consists of many species and varieties; the fruits can vary greatly in color, size, and shape. Taxonomical confusion exists in part due to extensive plant breeding.

The plant has straight, woody stems and can grow to approximately 3 m tall in tropical conditions. Star-shaped, white flowers are located in the axils of the leaves, which later become the varied-colored peppers. These fruits contain many flat, white seeds that are the primary source of the chili spice.1, 2 The capsicum fruit was probably termed a pepper because of the burning sensation similar to that of black and white pepper spices of the unripened fruit of the unrelated Piper nigrum.

History

Capsicum was first described in the mid-1400s by a physician who accompanied Columbus to the West Indies. The plants derive their names from the Latin capsa (box), which refers to the partially hollow, box-like fruit.

Capsicum has been highly desired as a spice and has been cultivated in some form in almost every society. Peppers are among the most widely consumed spices in the world, with an average daily per capita consumption in some Southeast Asian countries approaching 5 g of red pepper, corresponding to approximately 50 mg of capsaicin.3

Combination homeopathic and natural preparations contain capsicum extracts, and capsicum is used in traditional Korean medicine.4, 5, 6 Over-the-counter products are marketed for relief of oral discomfort or toothache, external analgesia, as a digestive aid, in menstrual conditions, and in cosmetics as cleansers and bath products.4

Chemistry

Capsicum contains approximately 1.5% of the irritant oleoresin. The major component of the oil is capsaicin (0.02%), a very pungent phenolic chemical. Along with several closely related compounds, it is responsible for the pungency of the fruit.4 The structure of capsaicin (8-methyl-N-vanillyl-6-nonenamide)4, 7 is similar to that of eugenol, the active principle in oil of cloves, which can also induce long-lasting local analgesia.8 The pungency appears to be related to the presence of a 4-hydroxy-3-methoxyphenyl substituent.9 It has been noted that the more tropical the climate in which the plant originates, the more pungent the fruit; however, extremely pungent peppers can be grown in any climate.10 The characteristic flavor of capsaicin in aqueous solutions can be detected in concentrations as low as 1 part in 11 million.

Other capsaicinoids present in capsicum include homocapsaicin, norhydrocapsaicin, dihydrocapsaicin, and homodihydrocapsaicin. Flavonoids, fatty acids, carotene, vitamins A and C, citric, tartaric, malic and tannic acids, and thiamine have also been identified in the fruits.4

Uses and Pharmacology

The widespread use of capsicum as a food has made experiments in animals largely irrelevant, aside from those investigating a role in cancer and those attempting to investigate the mechanisms of action.

Cough challenge

Capsaicin induces a dose-dependent and reproducible cough and is used in cough-challenge testing.50 The safety of inhaled capsaicin for this purpose has been reviewed (122 studies were included), with no serious adverse event reported.51

Diabetes/Obesity

Animal data

The role of capsicum in diabetes is uncertain.9, 11 Animal experiments show both positive and negative effects on glucose metabolism and insulin secretion. Limited clinical trials exist. A reduction in postprandial hyperinsulinemia was achieved with 30 g of freshly chopped chili daily over 4 weeks, but no reduction in the glucose area under the curve (AUC) or peak glucose levels were shown.12

Clinical data

A small clinical study (n=12) evaluated the effect of oral capsaicin on plasma glucose and insulin levels. Initial reductions in plasma glucose (30 and 45 mins after a 5 g dose) and elevated insulin levels were reported at 60 to 120 minutes.82

Antioxidant activity has been demonstrated in vitro and in the clinical setting13, 14, 15 but with no significant difference in serum lipids, lipoproteins, or total antioxidant status.14

Capsicum has been used for weight reduction, although clinical evidence is insufficient to support this use.9, 29 A clinical trial evaluated the safety of 6 mg/day of capsaicinoids over 12 weeks for weight loss30 while another used 30 g/day of fresh chili containing approximately 55% cayenne chili for 4 weeks14; weight loss was not achieved in either trial. Loss of abdominal fat was achieved in the 12-week trial.30

Gastrointestinal effects

Animal data

Animal studies suggest capsaicin exerts varying effects on gastric motility and is protectant against mucosal lesions induced by aspirin, ethanol, or hydrochloric acid.16, 17, 18

Clinical data

Clinical trials have had varying results, possibly because of the design of the studies. One study found no difference in the healing rate of duodenal ulcers among patients who ingested 3 g of capsicum daily compared with untreated controls.19

Red chili ingested daily over 3 weeks resulted in an increased secretion of gastrin, while a chili-rich diet lowered gastrin secretion.16 Repeated exposure of the esophageal mucosa to red chili pepper sauce initially increased heartburn, but subsequently exerted an analgesic effect20 and 2.5 g of red pepper daily over 5 weeks resulted in a decrease in the intensity of dyspepsia after 3 weeks. A mechanism of initial sensitization, followed by desensitization of gastric nociceptive C-fibers, has been suggested.21 In other studies, capsaicin decreased gastric liquid emptying18 and low-dose capsaicin was suggested to stimulate the swallowing reflex.22

A study of the effects of red chili consumption following hemorrhoidectomy concluded that in the postoperative period, the increased extent and duration of typical postoperative symptoms (pain, anal burning, and bleeding) warranted chili consumption as a contraindication.23 However, a single-dose randomized clinical trial found no effect on hemorrhoidal symptoms.24 A further clinical trial resulted in increased symptoms of pain and burning, but not pruritus, in patients with acute anal fissures consuming 3 g/day of dried chili powder over 2 weeks.25

Although capsaicin has shown inhibitory action on Helicobacter pylori in vitro, an in vivo study does not support this action.26 The validity of the study has been questioned because of the small number of subjects and the short study duration.27, 28

Pain

Most clinical studies report a significant number of adverse events and high drop-out rates associated with the burning sensation induced by topical capsaicin.31, 32, 33, 34, 35, 36, 37

Capsaicin acts as a selective agonist for the transient receptor potential vanilloid 1 receptor on afferent neurons specialized for the detection of noxious sensations. Topical capsaicin acts primarily on sensory-C fibers to cause depletion of substance P from the nerve terminals. This, in turn, causes desensitization of the sensory afferents.8, 38

The American Academy of Neurology clinical practice guideline states that the degree of pain relief from topical capsaicin is below the level considered clinically important for the treatment of chronic pain.39 A Cochrane systematic review of studies of herbal therapies for nonspecific lower back pain found moderate evidence of short-term effect for topically applied capsaicin, either as a cream or plaster, in reducing pain and improving function.40, 83 A review of studies evaluating topical capsaicin in chronic pain calculated a number needed to treat (NNT) value of 5.7 for capsaicin 0.075% cream at 8 weeks for a 50% reduction in pain associated with neuropathic conditions versus placebo, and an NNT of 8.1 for pain of musculoskeletal origin for 0.025% topical capsaicin at 4 weeks.37 A systematic review on herbal therapies in rheumatoid arthritis found one well-designed trial using 2 different measures of pain in which capsaicin performed better than placebo.35

A Cochrane systematic review of topical herbal products for osteoarthritis (OA) found one clinical trial (n = 99) in knee OA, with capsicum extract gel failing to provide a significant benefit versus placebo for pain relief or joint function.79

Mixed results have been obtained for the effect of topical capsaicin in pain associated with HIV neuropathy.33, 34, 41 A high concentration dermal patch (8% w/w capsaicin) showed a reduction in pain for up to 12 weeks after application after a transient, treatment-related increase in pain for the first day. Duration of application of the patch (30, 60, or 90 minutes) was not clearly established in the randomized clinical study.33 Another smaller trial found no benefit at 4 weeks with 0.075% topical capsaicin.34

The instillation of capsaicin powder into the wound during hernia repair has also been evaluated, with analgesic effect demonstrated for up to 3 days after the incision.36 The use of capsaicin plasters applied to relevant acupuncture points in reducing the requirement for postoperative analgesia has been evaluated, with efficacy being demonstrated against placebo and "sham" pressure points.5, 42

Capsaicin cream (either 0.025% or 0.075%) was effective when applied topically in the management of postherpetic neuralgia.43 It has been evaluated in the management of pain from other causes, including trigeminal and diabetic neuralgia, osteoarthritis, postsurgical neuralgias4, 44 and vulvar vestibulitis.45 High-dose (5% to 10%) topical capsaicin has also been investigated in intractable pain.46 Intravesical capsaicin has decreased frequency and nocturia of patients with severe bladder pain.47 Repeated instillations of intravesical capsaicin were shown to be effective for 3 to 5 years in treating detrusor hyperreflexia caused by spinal cord disease.48 Intraureteric capsaicin instillation was shown to provide dramatic symptomatic relief in some patients with loin pain hematuria syndrome.49

Postoperative nausea

A limited number of studies suggest capsicum plasters applied to relevant acupuncture pressure points (K-D2 and P6 Korean points) are effective in reducing postoperative nausea.6, 52, 53

Pruritus

Topical capsaicin has been shown to effectively treat pruritus associated with psoriasis54, 55 pityriasis rubra pilaris56 psoralen-ultraviolet-light (PUVA) treatment57 prurigo nodularis58 and pruritus ani.59 However, large, high-quality clinical trials are lacking.

Psoriasis

An evidence-based review of botanicals for dermatologic conditions pointed out the data from two 6-week clinical trials (n = 241) on the use of capsaicin cream on psoriasis. Capsaicin was superior to placebo for relief of symptoms of scaling, thickness, erythema, and pruritus. Burning at the application site was the most commonly reported adverse effect.80

Rhinitis

A Cochrane review of the efficacy of inhaled capsaicin in allergic rhinitis found insufficient evidence to support clinical use.60 Only one trial met the inclusion criteria for the review, with a lack of adequate randomization being an issue in the other trials. In a small study, rhinitis, sneezing, and congestion were alleviated in 8 volunteers who received repeated nasal sprays of capsaicin.61 In a placebo-controlled study, intranasal capsaicin was shown to be effective in reducing nasal symptomatology in nonallergic, noninfectious perennial rhinitis without affecting cellular homeostasis up to 9 months after treatment.62, 63 A randomized, placebo-controlled, 2-week study (n = 42) evaluated a proprietary product, ICX72 or Sinus Buster, in adults with nonallergic rhinitis. Active treatment was significantly better than placebo for the total nasal symptom score, and individual symptoms scores for nasal congestion, sinus pressure, sinus pain, and headache. Results were not significantly better for active treatment compared with placebo for sneezing, rhinorrhea, or rescue medication use.81

Dosing

For external uses, capsaicin and capsicum creams are available in several strengths, from capsaicin 0.025% to 0.075%, and are applied up to 3 to 5 times daily.

Capsicum plasters containing powdered capsicum 345.8 mg and capsicum 34.58 mg tincture per sheet (12.2 × 16.4 cm2) have been evaluated for postoperative pain and nausea.5, 6

A high-concentration dermal patch (8% w/w capsaicin) has been used in HIV-associated neuropathy33 and intractable pain.45 Low-strength (0.006%) capsaicin ointment was used in a trial of itching in pruritus ani; higher strengths resulted in anal burning.59

A clinical trial evaluated the safety of capsaicinoids 6 mg/day over 12 weeks for weight loss30 while another used 30 g/day of fresh chili containing approximately 55% of cayenne chili for 4 weeks14 although weight loss was not achieved in either trial.

Pregnancy / Lactation

Capsaicin peppers are generally recognized as safe when used as food. Safety and efficacy for dosages above those in foods are unproven and should be avoided.

Studies in animals have shown both positive and negative effects. Capsaicin crosses the placenta and was shown to deplete substance P in the fetus with neurotoxic effect. Growth rates of rat pups were lower, and abnormal testicular descent was noted in pups born to capsaicin-fed rats. However, no differences in rat pup malformations, epididymal or testicular weight, or plasma progesterone were demonstrated in other experiments.4

Interactions

Experimental data exist64 including a case report65 of capsaicin-initiated or exacerbated captopril-induced cough. A mechanism has not been established. A similar interaction could be expected to occur with other ACE inhibitors and capsaicin. Consumption of chili was found to inhibit nonheme iron absorption from an iron-fortified composite meal and is suggested to be caused by binding to phenolic compounds in the chili.66

Adverse Reactions

Allergies to latex, bananas, kiwi, chestnut, or avocado may predispose people to capsicum (pepper) allergy.68 Allergic reaction to paprika has been seen in patients with "mugwort-celery-spice" syndrome. These patients exhibit allergy to mugwort, birch-pollen, celery, anise, coriander, cumin, fennel, and green and black peppercorns, as well as with fresh bell peppers and dried bell pepper fruits (paprika).69

Defense spray

The use of capsicum oleoresin as a defense spray results in burning in the throat, wheezing, dry cough, shortness of breath, gagging, gasping, and, rarely, cyanosis, apnea, and respiratory arrest.4, 70 A review concluded that the effects of capsicum defense spray on the conjunctiva and the cornea are generally mild and temporary, with corneal abrasion noted in approximately 7% of cases.70

Diabetes

Animal experiments show both positive and negative effects on glucose metabolism and insulin secretion. Clinical evidence of adverse effect is lacking.10, 11

Gastrointestinal

Increased extent and duration of typical postoperative symptoms (pain, anal burning, and bleeding) were found in posthemorrhoidectomy and acute anal fissure patients with chili consumption.23, 25 However, a single-dose, randomized clinical trial found no effect on hemorrhoidal symptoms.24 No clinically important adverse events were reported in a clinical trial evaluating capsaicinoids 6 mg/day for 12 weeks. Dyspepsia and bowel irregularities, including diarrhea, were recorded in a few participants.30

Skin

Topical irritation is common, particularly with the use of commercial creams, but contact dermatitis from the fruit has also been reported.4, 71 Most clinical studies report high dropout rates and adverse events associated with the burning sensation induced by capsaicin.31, 32, 33, 34, 35, 36, 37 Topical capsaicin should not be applied to the face or injured skin.80

Toxicology

The toxicology of Capsicum has been reviewed in general and with a focus on its use in the cosmetics industry.4 Short-term oral toxicity of C. annum in rats was considered to be relatively low.4, 72, 73 For C. frutescens, increases in lymphocytes and liver function tests and decreases hemoglobin, red blood cell count, total protein, albumin, cholesterol, and copper were seen with a diet containing Capsicum 10% after 8 weeks.4 Exfoliation of the intestinal epithelium and histological changes in the hepatocytes were also demonstrated at this dosage, but not at lower dosages.4 Some studies of chronic oral toxicity have shown little toxicity, while one study evaluating 5 mg/kg body weight of C. annum powder over a year showed moderate-marked histological changes in rabbit spleen and liver.4

Epidemiological and case-control studies have shown a 2- to 3-fold increase in the risk of cancers, including oral, pharyngeal, esophageal, and laryngeal, and a trend toward an increased risk for gall bladder, stomach, and colon cancers with chili consumption.4, 74 There are mixed results for capsaicin as a carcinogen, cocarcinogen, and anticarcinogen.4, 74, 75, 76, 77, 78

Inhalation

Studies on workers with long-term exposure to chili dust report initial cough, sneezing, and rhinitis, as well as chronic symptoms in some workers. However, chest radiographs were normal and no differences in ventilatory measurements were observed.4, 51

References

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