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BROMELAIN

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Bromelain is a complex of sulfhydryl-containing proteolytic enzymes obtained from the stem of the pineapple plant (Ananas comosus). Bromelain also contains a peroxidase, acid phosphatase, several protease inhibitors, and organically bound calcium. Bromelain does not disappear as the fruit ripens.

Specific Substances

    1) Bromelain
    2) Ananase
    3) Bromelin
    4) Extranase
    5) Inflamen
    6) Traumanase

Available Forms Sources

    A) SOURCES
    1) Bromelain is a complex of sulfhydryl-containing proteolytic enzymes obtained from the stem of the pineapple plant (Ananas comosus). It is found in both the stem and the fruit.
    B) USES
    1) FOLK MEDICINE: Pinapple juice has been used against quinsy, as a digestive aid, and externally against horny skin (Lotz-Winter, 1990).
    2) CURRENT RECOMMENDATIONS: Treatment for inflammation associated with edema, inflammation of the respiratory tract, inflammations of the circulation such as venous ulcers or thrombophebitis, and to enhance the activity of certain antibiotics (Lotz-Winter, 1990).

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Bromelain is being investigated for its keratolytic, hematologic, and antiedema properties in animals. When given orally, there are minimal effects. Possible gastritis and a few dermatologic effects due to its proteolytic nature have been noted.
    B) Ingestions should not be treated aggressively.
    0.2.5) CARDIOVASCULAR
    A) Mild hypotension and bradycardia were seen in dogs when bromelain was injected rapidly, but not slowly. These effects have not been seen in humans.
    0.2.6) RESPIRATORY
    A) Asthma has been reported following occupational exposure to bromelain.
    0.2.8) GASTROINTESTINAL
    A) Mild gastritis or oral irritation may occur after ingestion of bromelain.
    0.2.14) DERMATOLOGIC
    A) Keratolytic effects may occur with chronic handling of plants containing bromelain. The enzyme has been used to remove horny epidermis.
    0.2.19) IMMUNOLOGIC
    A) Sensitization has occurred in animals injected with bromelain.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

    A) No specific measures are indicated after ingestion.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Ingestion of bromelain is minimally toxic, usually producing only mild gastritis. Gastric evacuation/decontamination would usually not be necessary, unless large amounts of actual bromelain were to be ingested. No specific toxic dose has been established in humans.
    B) EMESIS - Is generally not necessary.
    C) ACTIVATED CHARCOAL - Is generally not necessary.
    D) Treatment is symptomatic and supportive.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and irrigate exposed areas with copious amounts of water. A physician may need to examine the area if irritation or pain persists.

Range Of Toxicity

    A) No specific toxic dose has been established for humans. The oral LD50 in rodents is greater than 10 grams per kilogram.

Summary Of Exposure

    A) Bromelain is being investigated for its keratolytic, hematologic, and antiedema properties in animals. When given orally, there are minimal effects. Possible gastritis and a few dermatologic effects due to its proteolytic nature have been noted.
    B) Ingestions should not be treated aggressively.

Cardiovascular

    3.5.1) SUMMARY
    A) Mild hypotension and bradycardia were seen in dogs when bromelain was injected rapidly, but not slowly. These effects have not been seen in humans.
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPOTENSION
    a) When injected rapidly, hypotension (a drop of 30 to 40 mmHg) and a reduction in heart rate of 22 to 26 beats per minute were seen in anesthetized dogs (Neiper, 1976). These effects did not occur when bromelain was injected slowly.

Respiratory

    3.6.1) SUMMARY
    A) Asthma has been reported following occupational exposure to bromelain.
    3.6.2) CLINICAL EFFECTS
    A) ASTHMA
    1) Occupational exposure to bromelain has resulted in allergic reactions including asthma. In one case series, 4 patients developed bronchial asthma or wheezing in addition to symptoms such as rhinitis, eye irritation, and difficulty swallowing after handling bromelain. Skin prick tests done in 3 patients were positive. In another case, a 58-year-old female developed asthma and rhinitis after handling bromelain in a pharmaceutical plant, with RAST and skin prick tests showing positive reactions (Baur & Fruhmann, 1979; Gailhofer et al, 1988).

Gastrointestinal

    3.8.1) SUMMARY
    A) Mild gastritis or oral irritation may occur after ingestion of bromelain.
    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL IRRITATION
    1) Oral irritation, including a burning sensation of the mouth and lips may occur when eating bromelain containing fruit (Watt & Breyer-Brandwijmk, 1962).

Dermatologic

    3.14.1) SUMMARY
    A) Keratolytic effects may occur with chronic handling of plants containing bromelain. The enzyme has been used to remove horny epidermis.
    3.14.2) CLINICAL EFFECTS
    A) DISORDER OF SKIN
    1) Workers who are exposed to the keratolytic effects of bromelain while picking pineapples had the stratum corneum of the fingers removed, resulting in the obliteration of fingerprints (Mitchell & Rook, 1979).

Immunologic

    3.19.1) SUMMARY
    A) Sensitization has occurred in animals injected with bromelain.
    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ALLERGIC REACTION
    a) Injection of bromelain produced sensitization in animals (Lotz-Winter, 1990).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific measures are indicated after ingestion.
    4.1.2) SERUM/BLOOD
    A) OTHER
    1) No specific laboratory measures are indicated.

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) No specific measures are indicated after ingestion.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS
    1) Is generally not required due to low oral toxicity.
    B) ACTIVATED CHARCOAL
    1) Is generally not required due to low oral toxicity.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Bromelain has not been shown to be significantly toxic orally. The potential gastritis can be handled with supportive care.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Summary

    A) No specific toxic dose has been established for humans. The oral LD50 in rodents is greater than 10 grams per kilogram.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) HUMAN DATA -
    a) Therapeutic benefits of bromelain have been observed with 160 milligrams daily, with best results occurring at 750 to 1000 milligrams daily (Anon, 1998).

Maximum Tolerated Exposure

    A) ANIMAL DATA
    1) RATS - Chronic administration of 1 percent bromelain in the food of rats produced no significant changes (Lotz-Winter, 1990).
    2) DOGS - Chronic administration of increasing levels of bromelain to dogs (up to 750 mg/kg daily) did not show any signs of toxic effects after 6 months (Anon, 1998). .

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 36.7 mg/kg (Batkin et al, 1988)
    B) LD50- (ORAL)MOUSE:
    1) > 10 g/kg (Batkin et al, 1988)
    C) LD50- (INTRAPERITONEAL)RAT:
    1) 85.2 mg/kg (Batkin et al, 1988)
    D) LD50- (ORAL)RAT:
    1) > 10 g/kg (Batkin et al, 1988)

Pharmacologic Mechanism

    A) Bromelain is actually a complex of at least 5 closely related enzymes that differ somewhat as to substrate and optimum operational pH, but they are closely related enough that they are generally thought of as a single compound (Lotz-Winter, 1990).
    B) The optimum pH for operation is 7 (Lotz-Winter, 1990).
    C) Bromelain will operate on many protein substrates, including casein, muscle fibers, gelatin, collagen, and globulins (Lotz-Winter, 1990).
    D) Bromelain has an anti-edema effect when given enterally to rats in doses of 80 mg/kg (Ulig & Seifert, 1981). Other studies have shown antiedema effects on induced footpad edema in animals (Pirotta & De Giuli-Morghen, 1978; Sugio & Daly, 1983; Martin et al, 1962).
    1) Reduction of capillary permeability is due to tissue kininogenins (DiRosa et al, 1971), and reduction of lung and bronchial edema are due to irritants (DiRosa et al, 1971) Suda et al, 1984).
    E) Anti-inflammatory effects may be due to several mechanisms including inhibition of bradykinin through depletion of the plasma kallekrein system, inhibition of the formation of fibrin by reduction of clotting cascade intermediates, and stimulation of plasminogen conversion to plasmin (Anon, 1998).
    F) Circulatory system effects include (Smyth et al, 1961; Livio et al, 1978):
    1) Platelet aggregation inhibition
    2) Increased prothrombin time
    3) Increased antithrombin levels
    4) Increased plasmin level
    G) Effects on enzymes include:
    1) Inhibition or degradation of bradykinin (Anon, 1998; Suda et al, 1984; Shigei et al, 1967).
    2) Effects prostoglandin synthesis (Vellini et al, 1986).

Physical Characteristics

    A) Bromelain is a white to tan amorphous powder (HSDB, 2005)

Molecular Weight

    A) STEM Bromelain: approximately 33,000

General Bibliography

    1) Anon: Bromelain. Alternative Medicine Review 1998; 3:302-5.
    2) Baur X & Fruhmann G: Allergic reactions, including asthma, to the pineapple protease bromelain following occupational exposure. Clin Allergy 1979; 9:443-450.
    3) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    4) DiRosa M, Giroud JP, & Willoughby DA: J Pathol 1971; 104:15.
    5) Gailhofer G, Wilders-Truschnig M, & Smolle J: Asthma caused by bromelain: an occupational allergy. Clin Allergy 1988; 18:445-450.
    6) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 2005; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    7) Livio M, Bertoni MP, & De Gaetano G: Drugs Exptl Clin Res 1978; 4:49.
    8) Lotz-Winter H: On the pharmacology of bromelain: an updated with special regard to animal studies on dose-dependent effects. Planta Medica 1990; 56:249-253.
    9) Martin G, Ehrenreich J, & Asbell N: Exp Med Surg 1962; 20:227.
    10) Mitchell J & Rook A: Botanical Dermatology, Greengrass, Vancouver, BC, 1979.
    11) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    12) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    13) Pirotta F & De Giuli-Morghen C: Drugs Exp Clin Res 1978; 4:1.
    14) Smyth RD, Brenan RM, & Martin GJ: Am J Pharm 1961; 133:294.
    15) Sugio K & Daly JW: Life Sci 1983; 33:65.