The effect of orally administered Bromelain or the reduction of swelling, bruising, healing time, and pain following
various surgical procedures has been demonstrated in several clinical studies. 6,18,19,20 In the study by Tassman,
et al,18after oral surgery, swelling decreased within 3.8 days with Bromelain, compared with 7 days for the placebo
in a double-blind study. In the same study, pain duration was reduced within 5.1 days in the Bromelain group,
compared with 8.1 days in the placebo group.
Recently, in an open case observation study involving patients with blunt injuries to the musculoskeletal system, the
efficacy and tolerability of high-dose Bromelain was investigated by an orthopedic surgeon. In addition to usual
therapeutic measures, 59 patients were treated with Bromelain preparations for one to three weeks based upon
healing response. Treatment with Bromelain resulted in clear reduction of swelling, pain at rest and during
movement, and tenderness to palpation. The addition of Bromelain to the treatment regime accelerated the rate of
healing compared to the usual rate of healing observed for blunt injuries to the musculoskeletal system. The
tolerability of the Bromelain preparation was very good, and patient compliance was correspondingly high.21
Experimental Investigations Demonstrating The Anti-inflammatory Properties of Bromelain
Recent reviews have confirmed the analgesic, anti-inflammatory and edema-reducing properties of Bromelain and
other proteolytic enzyme combinations.1,16
As reported by Kleef, et al, Bromelain-treated lymphocytes from healthy human donors displayed a 60 percent to
90 percent reduction in cell surface adhesion compared to untreated lymphocytes in vitro. The selective
modulation of cell adhesion molecules may help explain some of the clinical effects observed after Bromelain
treatment in patients suffering from chronic inflammatory disease, HIV and cancer.22
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Meschino Health Comprehensive Guide to Herbs
Over the past few years, a number of studies have demonstrated the effects of oral enzymes, including Bromelain,
on suppressing the synthesis of pro-inflammatory cytokines14,34 and adhesion molecules,22,35 the latter are
expressed on the surface of cells, enabling cell-cell interactions, which are fundamental processes of the
inflammatory reaction.36,37
In summary, oral enzyme therapy reduces various parameters of inflammation and pain by affecting the release of
mediators of inflammation, modulation of adhesion molecules, reduction of immune complexes, activation of
fibrinolysis and direct influences on nociceptors.14,16
3. Digestive Aid
Bromelain in combination with other digestive enzymes and ox bile has been reported to help digest food 41, but is
not generally used alone for this purpose.
Dosage
Anti-inflammatory: 250-750 mg, three times daily on an empty stomach. Bromelain is often standardize to 2,000 milk
clotting units (MCU) which is 1333.3 Gelatin Dissolving Units (GDU) 38,47
Adverse Side Effects and Toxicity
Currently, NSAIDs are first-line therapy in osteoarthritis. However, endoscopic studies have shown that lesions of the
gastric mucosa developed in 14 to 31 percent of patients receiving long-term treatment with NSAIDs.23,24,25,26 In
particular, the elderly may be seven times more likely to have silent ulcers from NSAID use.24,25,27,28 Other potential
adverse effects of NSAIDs include cardiac, renal, hepatic and central nervous system damage.14 From an economic
standpoint, the treatment of gastrointestinal adverse effects from NSAIDs has been calculated to add 45 percent to the
cost of arthritis care. 29,30
By comparison, therapy with oral enzymes is not associated with severe gastrointestinal irritation, erosion, ulcerations,
and related risks 14,1 and is generally well tolerated.14, 21,31,32,33
Determination of pepsinogen A and C, which are indicators of the function and morphological condition of the gastric
mucosa, confirmed good gastric tolerability with administration of oral enzymes, including Bromelain.14
Unpublished data from trials of up to 4 years duration in patients with various clinical conditions (i.e. rheumatoid
arthritis, multiple sclerosis) suggest that oral enzyme therapy, including Bromelain, is very well tolerated over longer
periods.14
In regards to toxicity, animal studies have shown no toxic effects with Bromelain doses up to 10 grams per kilogram as
no LD50 (50 percent lethal dose) exists for Bromelain doses in this range.38
Drug-Nutrient Interactions
1. Anticoagulant Medications (warfarin, coumadin etc) - In regards to potential adverse drug-nutrient interactions,
studies using Bromelain on isolated human platelets in vitro revealed that Bromelain prevented thrombin-induced
platelet aggregation, whereas papain enzyme was less active in preventing platelet aggregation. There is strong
biological plausibility that Bromelain may further potentiate the anti-clotting influence of warfarin and coumadin,
potentially increasing risk of a bleeding disorder. As well, animal studies and reports with humans indicate that
Bromelain treatment can reduce thrombus formation via its thrombolytic action. To date there are no published
reports of bleeding disorders occurring in humans using Bromelain supplementation. However, until more
information is available, it is advisable to use caution and proper patient monitoring (prothrombin time, INR), when
recommending Bromelain to patients on warfarin or anticoagulant therapy.39,40
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Meschino Health Comprehensive Guide to Herbs
2. Antibiotics – Bromelain has been shown to increase the amount of antibiotics in the blood and urine with
concurrent orally administration.42,43,44,45,46
Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal
vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the
developing fetus and there is generally insufficient evidence at this time to determine an absolute level of
safety for most dietary supplements other than a prenatal supplement. Any supplementation practices
beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium
and the treatment of preeclampsia.)
References: Pregnancy and Lactation
1.
Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.
2.
Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and
Company Inc. 1998.
3.
The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.
4.
Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine.
Institute of Applied Complementary Medicine Inc. 1997.
1. 5.. Tausssig SJ et al. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J
Ethnopharmacol. 1988;2:191-203
2.
Ako H et al. Isolation of fibrinolysis enzyme activator from commercial Bromelain. Arch Int Pharmacodyn. 1981;254:157-67
3.
Taussing S. The mechanism of the physiological action of Bromelain. Med Hypothesis 1980;6:99-104
4.
Seligman B. Bromelain: an anti-inflammatory agent. Angiology. 1962;13:508-10
5.
Pirotta F et al. Bromelain – a deeper pharmacological study. Note I. Anti-inflammatory and serum fibrinolytic activity after oral
administration in the rat. Drugs Exp Clin Res. 1978;4:1-20
6.
Tassman G et al. Evaluation of a plant proteolytic enzyme for the control of inflammation and pain. J Dent Med 1964;19:3-77
7.
Felton G. Does kinin released by pineapple stem Bromelain stimulate production of prostaglandin E1-like compounds? Hawaii Med J
1977;36:39-47
8.
Katori M et al. A possible role of prostaglandins and bradykinin as a trigger of exudation in carrageenan-induced rat pleurisy. Agents
Action 1978;8:108-12
9.
Miller J et al. The increased proteolytic activity of human blood serum after oral administration of Bromelain. Exp Med Surg 1964;22:277-
80
10. Izaka K et al. Gastrointestinal absorption and anti-inflammatory effect of Bromelain. Jpn J Pharmacol 1972;22:519-34
11. Seifert J et al. Absorption of a proteolytic enzyme of plant origin from the gastro-intestinal tract into the blood and lymph of adult rats. Z
Gastroenterol 1979;17:1-18
12. Castell JV et al. Intestinal absorption of undegraded proteins in men: presence of Bromelain in plasma after oral intake. Am J Physiol
1997;273:139-46
13. Cohen A et al. Bromelain therapy in rheumatoid arthritis. Pennsyl Med J 1964;67:27-30
14. Klein G et al. Short-term treatment of painful osteoarthritis of the knee with oral enzymes : A randomized, double-blind study versus
diclofenac. Clin Drug Invest 2000;19 (1):15-23
15. Singer F et a. Therpie der aktivierten Arthrose: Zur effektivitat eines enzymgemisches versus diclofenac. Wien Med Wochenschr
1996;3:55-8
16. Klein G et al. Reducing pain by oral enzyme therapy in rheumatic diseases. Wein Med Wochenschr 1999;149:577-80
17. Blonstein J. Control of swelling in boxing injuries. Practitioner 1960:203-6
18. Tassman G et al. A Double-blind crossover study of a plant proteolytic enzyme in oral surgery. J Dent Med 1965;20:51-4
19. Howat R et al. The effect of Bromelain therapy on episiotomy wounds – a double-blind controlled clinical trial. J Obstet Gynecol Br
Common 1972;79:951-3
20. Ztuchni G et al. Bromelain therapy for the prevention of episiotomy pain. Obstet Gynecol 1967;29:275-8
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Meschino Health Comprehensive Guide to Herbs
21. Masson M. Bromelain in blunt injuries of the locomotor system. A study of observed application in general practice. Fortschr med
1995;113:303-6
22. Kleef R et al. Selective modulation of cell adhesion molecules of lymphocytes by Bromelain protease. Pathobiology 1996;64:339-46
23. Baskin WN et al. Aspirin-induced ultra structural changes in human gastric mucosa: correlation with potential difference. Ann Intern Med
1976;85:299-303
24. Miller DR. Treatment of nonsteroidal anti-inflammatory drug induced gastropathy. Clin Pharm 1992;11:690-704
25. Shallcross TM et al. Effect of nonsteroidal anti-inflammatory drugs on dyseptic symptoms. BMJ 1990;300:368-9
26. Soll AH et al. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med 1991;114:307-19
27. Clinch D et al. Absence of abdominal pain in elderly patients with peptic ulcers. Age Ageing 1984;13:120-3
28. Singh G et al. Gastrointestinal trct complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis. A prospective
observational cohort study. Arch Intern Med 1996;156:1530-6
29. Bloom BS. Direct medical costs of disease and gastrointestinal side effects during treatment for arthritis. Am J Med 1988;84
Suppl(2A):20-4
30. Green JM et al. Cost-conscious prescribing of nonsteroidal anti-inflammatory drugs for adults with arthritis. Arch Intern Med
1992;152:1995-2002
31. Miehlke K. Rheumabehandlung mit enzymen ist mehr als nur antiphlogistische therapie. In: Medizinische Enzym-Forschungs-
gesellschaft e.V.systemishe Enzym-therapie,15th working symposium, Munich, German. Grafelfing: Forum Medizin Verlag 1991
32. Miehlke K. Enyme minimieren Risiken der Rheymatherapie. In: Medizinische Enzym-Forschungs-gesellschaft e.V.Systemische
Enzymtherapie, 10th working symposium, Franfurt, germany. Grafelfing: Forum Medizin Verlag, 1990
33. Gutfreund A et al. Effect of oral Bromelain on blood pressure and heart rate of hypertensive patients. Hawaii Med J 1978;37:143-6
34. Lehmann VP. Immunomodulation of proteolytic enzymes. Nephrol Dial Transplant 1996;9:253-63
35. Munzig E et al. Bromelain protease F9 reduces the CD44 mediated adhesion of human peripheral blood lymphocytes t human umbilical
vein endothelial cells. FEBS Lett 1994;351:215-18
36. Mojcik C et al.Adhesion molecules. Arthritis Rheum 1997;40 :991-1004
37. Veale DJ et al. Cell adhesion molecules in rheumatoid arthritis. Drugs Aging. 1996;9:87-92
38. Murray M. The Healing Power of Herbs (2nd ed.) Prima Publishing 1995;Bromelain:60-9
39. Metzig C et al. Bromelain proteases reduce human platelet aggregation in vitro, adhesion bovine endothelial cells and thrombus
formation in rat vessel in vivo. In Vivo 1999;13(1):7-12
40. Heck A. Potential interactions between alternative therapies an warfarin. Am J Health-Syst Pharm. 2000;57(13):1221-7
41. Balakrishnan V et al. Double-blind cross-over trial of an enzyme preparation in pancreatic steatorrhea. J. Assoc. Phys. Ind. 1981;29:207-
9
42. Tinozzie S, Venegoni A. Efect of Bromelain on serum and tissue levels of Amoxycillin. Drugs Exptl Clin Res. 1978;4:39-44
43. Renzinni G, Varengo M. The absorption of tetracycline in combination with Bromelain by oral application. Arzneim-Forsch. 1972;22:410-
12
44. Luerti M, Vignali ML. Influence of broemlain on penetration of antiobiotics in uterus, salpinx and ovary. Drugs Exp Clin Res. 1978;4:45-8
45. Bradbook ID et al. The effect of Bromelain on the absorption of orally administered tetracycline. Dr J Clin Pharmacol. Dec1978;6(6) :552-
4
46. Lucchi R et al. Chronic infections of the lower respiratory tract. Antibiotic therapy. Results of a double-blind study: tetracycline-HCL as
monosubstance versus tetracycline and bromeline. ZFA (Stuttgart). Apr1980;56(11):807-12
47. Dietary Supplement Information Bureau. www.content.intramedicine.com:Bromelain
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Meschino Health Comprehensive Guide to Herbs
Capsicum (Capsicum Annuum)
General Features
Capsicum is one of the oldest and most widely used spices in the world. It is a member of the solanaceae family and
its synonyms include chili peppers, red pepper, cayenne pepper and hot pepper.1
Principle Active Constituents
Capsaicinoids, especially capsaicin.2
Clinical Application and Mechanism of Action
Pain Relief (topical agent)
As an ingredient in topical agents, capsaicin depletes substance P (SP), a substance that mediates pain transmission
from the peripheral nerves to the spinal cord.3,4
This occurs in four stages:
1. SP is immediately released from both central and peripheral terminals.
2. SP fibers become functionally impaired.
3. The axoplasmic transport of SP is inhibited.
4. SP is depleted.
(This begins after one day of use and may last for weeks).5
Diabetic Neuropathy
The Capsaicin Study Group has resulted in a number of trials that have proven the efficacy of topical application of
capsaicin for the relief of diabetic neuropathy. Most of the studies have used topical capsaicin 0.075% in a cream
base. In several published trials, approximately 90% of patients reported significant improvement in pain
relief.6,7,8,9,10,11
Post-herpetic Neuralgia
A lower strength capsaicin topical cream, containing 0.025% capsaicin has been used successfully in many trials and
provides significant relief of post-herpetic neuralgia pain. Approximately 40 – 70% of patients report improvement from
the available studies performed to date.12,13,14,15,16,17
Arthritis and Other Painful Conditions
Capsaicin cream has been reported to reduce the pain of rheumatoid arthritis,18 osteoarthritis18,19 cluster
headaches20,21 reflex sympathetic dystrophy22, idiopathic trigeminal neuralgia,23 and post-mastectomy pain
syndrome.24,25
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Meschino Health Comprehensive Guide to Herbs
Dosage and Standardized Grade
Topical Agent:
1. Diabetic neuropathy – 0.075% in a cream base.
2. Post-herpetic neuropathy – 0.025% in a cream base.
3. Arthritis and other listed painful conditions - either of the above concentrations can be utilized.1
Adverse Side Effects, Toxicity and Contraindications
The following adverse side effects have been reported for topical application of capsaicin creams:
1. Allergic contact dermatitis has been reported26,27 with topical cream.
2. Erythema; burning and stinging sensations (no vesication) common at both 0.025% and 0.075% concentrations
when applied topically. Intensity diminishes after 2 weeks.6,7,8,9 Inhalation reactions (coughing, sneezing) occur
occasionally 6,8 with topical application. The primary contraindication for topical use is known allergy to
Capsicum.1
Drug Interactions
There are no well- known drug-nutrient interactions for topical application of capsaicin creams.1
N.B.: Note that capsaicin is found in a variety of commercially available external analgesic preparations.1
Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal
vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the
developing fetus and there is generally insufficient evidence at this time to determine an absolute level of
safety for most dietary supplements other than a prenatal supplement. Any supplementation practices
beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium
and the treatment of preeclampsia.)
References: Pregnancy and Lactation
1. Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.
2. Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and
Company Inc. 1998.
3. The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.
4. Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine.
Institute of Applied Complementary Medicine Inc. 1997.
www.meschinohealth.com
38
Meschino Health Comprehensive Guide to Herbs
1. Boon H, Smith M. Health care professional training program in complementary medicine. Institute of Applied Complementary
Medicine Inc. 1997:53-60.
2. Leung AY, Foster S. Encyclopedia of common natural ingredients used in food, drugs, and cosmetics. , 2nd edition. Toronto/New
York. John Wiley and Sons Inc. 1996:649.
3. Tyler VE. Herbs of choice, the therapeutic use of Phytomedicinals. Binghamton, New York. Pharmaceutical Products Press
1994:2090.
4. Locock RA. Capsicum. Canadian Pharmaceutical Journal 1985;118:517-9.
5. Skofitsch G, Donnerer J, et.al. Comparison of nonivamide and capsaicin with regard to their pharmacokinetics and effects on
sensory neurons. Arzneimittell Forsch 1984;341:154-6.
6. Donofrio PD, Walker F, Hunt V, et.al. Treatment of painful diabetic neuropathy with topical capsaicin: a multicentre, double-blind,
behicle-controlled study. Archives of Internal Medicine 1991;151:2225-9.
7. Dailey GE. Effect of treatment with capsaicin on daily activities of patients with diabetic neuropathy. Diabetes Care 1992; 15(2):159-
65.
8. Scheffler NM, et.al. Treatment of painful diabetic neuropathy with capsaicin 0.075%. Journal of the American Podiatric Medical
Association 1991;81(6):288-93.
9. Basha KM, Whitehouse FW. Capsaicin: a therapeutic option for painful diabetic neuropathy. Henry Ford Hospital Medical Journal
1991; 39(2):138-40.
10. Pfeifer MA, et.al. A highly successful and novel model for treatment of chronic painful diabetic peripheral neuropathy. Diabetes
Care 1993; 16(8):1103-15.
11. Chad D, Ross D, Molitch M, et.al. Treatment of painful diabetic neuropathy with topical capsaicin – a double-blind multicentre
investigations. Pain 1990;42:387-8.
12. Watson CP, et.al. Post-herpetic neuralgia and topical capsaicin. Pain 1988;35:289-97.
13. Watson CP, Evans RJ, Wait VR, Birkett N. Post-herpetic neuralgia: 208 cases. Pain 1988;35:289-97.
14. Bernstein JE, Korman NJ, Bickers DR, Dahl MV, Millikan LE. Topical capsaicin treatment of chronic postherpetic neuralgia. Journal
of the American Academy of Dermatology 1989;21(2,Pt.1):265-70.
15. Bernstein JE, Bickers DR, Dahl MV, Roshal JY. Treatment of chronic postherapetic neuralgia with topical capsaicin, a preliminary
study. Journal of the American Academy of Dermatology 1987;17(1):93-6.
16. Bernstein JE. Capsaicin in the treatment of dermatologic disease. Cutis 1987;39:352-3.
17. Peikert A, Hentrich M, Ocas G. Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and
long-term course. Journal of Neurology 1991;238(8):452-6.
18. Deal CL, Schnitzer TJ, Lipstein E, et.al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clinical Therapeutics
1991;13(3):383-95.
19. McCarthy G, McCarty D. Effect of topical capsaicin on asteoarthritis of the hands. Journal of Theumatology 1992;19:604-7.
20. Sicuteri F, Fusco BM, Marabini S, et.al. Beneficial effect of capsaicin application to the nasal mucosa in cluster headache. Clinical
Journal of Pain 1989;5:49-53.
21. Marks DR, Rapoport A, Padla D, et.al. A double-blind, placebo-controlled trial of intranasal capsaicin for cluster headache.
Cephalalgia 1993;13(20):114-6.
22. Chesire WP, Snyder CR. Treatment of reflex sympathetic dystrophy with topical capsaicin. Pain 1990;43:307-11.
23. Fuscu BM, Alessandri M. Analgesic effect of capsaicin in idiopathic trigeminal. Neuralgia, Anesthesia and Analgesia
1992;74(3):375-7.
24. Watson CPN, Evans RJ, Watt VR. The post-mastectomy pain syndrome and the effect of topical capsaicin. Pain 1989;38:177-86.
25. Watson CP, Evans RJ. The postmastectomy pain syndrome and topical capsaicin: a randomized trial. Pain 1992;51(3):375-9.
26. Futrell JM, Tietschel RL. Spice allergy evaluated by results of patch tests. Cutis 1993;52:288-90.
27. Niinimaki A, Hannuksela M, Makinen-Kiljunen S. Skin prick tests and in vitro immunoassays with native spices and spice extracts.
Annals of Allergy, Asthma, & Immunology 1995;75:280-6.
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