Propolis exhibits antimicrobial action against gram-positive bacteria, yeasts, and some viruses. Commonly used in oral and dental preparations, propolis may have a role in reducing caries and oral ulcers and in promoting the health of injured teeth. Cytotoxicity of propolis and its chemical constituents has been demonstrated in various animal and in vitro models; however, clinical studies in cancer are lacking. Immune system effects, antioxidant actions, and effects on the cardiovascular system have also been described.
Dosing
There is limited clinical evidence to support specific dosage recommendations for propolis.
Contraindications
Contraindications have not yet been identified.
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented.
Adverse Reactions
Allergic reactions with skin and mucous membrane irritations have been reported. Sensitization to propolis, long recognized by apiary workers, has also been reported.
Toxicology
Information regarding toxicology is lacking.
Botany
Propolis is a natural resinous product collected from the buds of conifers and other trees by honeybees. It is used by bees to seal walls and strengthen combs of hives, as well as to embalm dead invaders. It is a sticky, greenish-brown mass with a slight aromatic odor.1, 2, 3, 4
History
Propolis has been used as a medicinal agent since ancient times. It was used in folk medicine as early as 300 BC for cosmetic purposes, for its anti-inflammatory properties, and for wound healing. It has been used internally and externally and is believed to possess antibacterial, antiviral, fungicidal, local anesthetic, antiulcer, anti-inflammatory, immunostimulant, hypotensive, and cytostatic properties.1, 2, 3
Chemistry
The composition of propolis varies with its geographic and plant source, as well as with the collection season.1, 4 The alcohol extract of propolis is called propolis wax or tincture, with the insoluble residue known as propolis resin.3, 5 Propolis contains 50% resin and vegetable balsam, 30% wax, 10% essential and aromatic oils, 5% pollen, and 5% other substances, including minerals such as magnesium, nickel, iron, calcium, and zinc.2, 3, 5
Propolis contains flavonoids, including quercetin, pinocembrin, galangin, and pinobanksin, as well as hydroquinone, caffeic acid, and caffeic acid esters.2, 3, 5 A number of other compounds have been identified in propolis from specific geographic sources.6, 7, 8, 9, 10
Uses and Pharmacology
Few high quality clinical trials have been undertaken. Researchers disagree over the importance of plant source and geographical variation on the spectrum of efficacy for propolis extracts.4, 11, 12, 13
Antimicrobial action
In vitro studies have shown broad-spectrum antimicrobial activity of various propolis extracts1, 2, 3, 6, 7, 9, 14, 15, 16, 17 although activity was highest in gram-positive bacteria and yeasts.5, 11, 17, 18, 19 Synergism with several antibiotics has been demonstrated.20 Antiviral action has also been demonstrated in animal and in vitro experiments, including activity against herpes simplex viruses types 1 and 2 and influenza viruses.5, 21, 22, 23 In clinical studies, propolis has been investigated for its activity against chronic vaginitis, genital herpes, and periodontal and respiratory tract infections; however, these studies are either unblinded, nonrandomized, or not compared with standard therapy, making definitive statements about efficacy difficult.1, 12, 24, 25, 26, 27 One pilot study (N = 18) investigated the effect of an ethanolic preparation of Brazilian green propolis on Helicobacter pylori.28 Twenty drops of the preparation taken 3 times a day for 7 days was not effective in eradicating H. pylori, despite in vitro studies showing that it inhibited bacterial growth.28 The researchers suggested that a trial with an increased dosage was warranted.
Antioxidant activity
Extracts of propolis have been investigated for their antioxidant properties, with some studies suggesting that the aqueous extract is more effective than the ethanolic, but not consistently so.1 Phenolic constituents isolated from propolis show more potent free-radical scavenging activity than caffeic acid and vitamins C and E.1 The antioxidant activity of propolis is considered to be 1 rationale for its proposed antitumor and hepatoprotective activity.1, 29, 30, 31
A reduction in exercise-induced oxidative stress was demonstrated in vitro for caffeic acid phenethyl ester, while a protective effect on ischemia/reperfusion injury in the brain and spinal cord of rats was also demonstrated.32, 33
A clinical study among healthy volunteers found no effect on oxidative status in women. In men, decreases in plasma malondialdehyde were observed at 15 days, and increased superoxide dismutase activity was observed at 30 days of treatment with daily powdered propolis containing 48.75 mg of flavonoids.34
Cancer
Cytotoxic activity of propolis and its chemical constituents has been demonstrated in breast, cervical, colonic, intestinal, liver, lung, prostate, and skin cancers and leukemia in various animal and in vitro models.1, 3, 8, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45 However, clinical studies are lacking.
Antiangiogenic effects have been demonstrated, as well as augmentation of natural defense mechanisms such as tumor necrosis factor and caspase pathways, and increased apoptosis by propolis and its constituents.5, 46, 47, 48, 49 Selective binding to human estrogen receptor beta (but not alpha), with no estrogenic effect on estrogen receptor-positive breast cancer cells, has been demonstrated in female rats.50 An aqueous extract of propolis was not protective against induced hepatocarcinogenesis in a study in rats.51
Prevention or reduction of hepatotoxicity due to chemotherapy has been demonstrated by propolis extracts in animal experiments.5, 52
Cardiovascular system effects
Antihypertensive, hypoglycemic, and antidyslipidemic effects have been described for propolis. In rats and in 1 clinical trial, an improved lipid profile was achieved in the serum and liver with administration of propolis.5, 53, 54 Total cholesterol increased much less with administration of propolis (+5.16 mg/dL) compared to controls (+28.96 mg/dL; P=0.01) in a 12-week double-blind, randomized, placebo-controlled trial conducted in 66 type 2 diabetics.90 Another clinical study among healthy volunteers found no effect on plasma lipid or glucose profile.34 A relaxant vasodilatory effect has been demonstrated on rat and porcine aorta and coronary artery segments, while the ethanolic fraction of propolis was hypotensive in rats.5, 55, 56
Diabetes
Decreased hyperglycemia has been demonstrated in a small clinical study with mulberry and propolis in patients with resistant type 2 diabetes.54 The effect of 900 mg/day bee propolis supplementation on glycemic, lipid, and insulin parameters in patients with type 2 diabetes was also evaluated in a 12-week double-blind, randomized, placebo-controlled trial (n=66). Mean FBG, HbA1c, and total cholesterol were found to be significantly different between groups. A significant decrease of −17.76 mg/dL was seen in the FBG with propolis compared to an increase of +6.48 mg/dL in controls (P=0.01) with similar results noted in HbA1c (−77% vs +0.19%; P=0.004). Additionally, total cholesterol increased much less in the propolis group (+5.16 mg/dL) compared to controls (+28.96 mg/dL; P=0.01). None of the other changes in lipid parameters or insulin indices differed significantly between groups.90
Immune system effects (eg, anti-inflammatory, wound healing)
A review of the effects of propolis extracts and individual chemical components has been published; however, clinical studies are limited.13 Effects on the immune system include macrophage activation, modulation of lymphocyte and antibody proliferation, cytokine production, and downregulation of transcription factors. Observed antitumor effects have been attributed to an enhanced immune response.5, 13, 57, 58, 59
Both orally administered propolis and topical applications improved wound healing, with increased wound closure rates and decreased inflammation in rodents.60, 61
Propolis exhibits anti-inflammatory effects in acute and chronic animal models.5, 62 The exact mechanism of action is unclear, but in vivo suppression of prostaglandin and leukotriene generation, as well as suppression of the lipoxygenase pathway of arachidonic acid metabolism have been demonstrated.1, 63 A 13% aqueous extract of propolis showed potent dose-related anti-inflammatory activity in rats comparable with the reference standard diclofenac64 while an in vitro experiment with human cartilage showed caffeic acid phenethyl ester to be more protective than indomethacin.65 A clinical study of the effect of propolis in asthmatic patients demonstrated a reduction in the frequency of asthma attacks, an increase in ventilatory function, and a decrease in inflammatory indicators prostaglandins and leukotrienes.66
Orodental use
Propolis is used as a mouthwash, toothpaste, oral gel, and throat lozenge because of its purported antibacterial and anti-inflammatory properties.
In vitro studies have shown activity against common periodontal pathogens, including Candida species and the Streptococci mutans group2, 12, 67 with 1 study suggesting that caffeic acid acts at the cellular level to influence epithelial membrane function against microbes.68 The use of propolis as a storage medium for teeth following avulsion has been investigated. Teeth stored in propolis demonstrated the highest number of viable cells when compared with milk, saline, and Hank's Balanced Salt Solution.69, 70 Similarly, propolis and caffeic acid phenethyl ester have been investigated for effect on traumatic injury to the teeth and activities on osteoclast maturation.71, 72
Clinical trials have shown the efficacy of propolis 500 mg in reducing the recurrence of aphthous stomatitis73 and propolis mouthwashes in reducing caries indicators (total bacterial and Streptococcus mutans counts).12 Propolis 2% rinse (20 mL for 30 seconds twice daily × 21 days) was shown to be as effective as sodium fluoride 0.05% plus cetylpyridinium chloride 0.05% rinse (positive control) for preventing gingivitis in a randomized, double-blind, co-twin trial (n = 42; 21 twin pairs).87 Administration of propolis led to significant reductions in mucositis grade (65% completely healed with propolis vs 0% in control), erythema, wounds, and eating and drinking ability whereas placebo yielded improvements in only wounds and mucositis scores in a randomized, double-blind controlled trial in 40 patients undergoing chemotherapy for head and neck cancer.89 Although a number of trials have documented benefits of supplemental propolis for oral health, significant benefit could not be demonstrated for various interventions (ie, oral infection, dental plaque, stomatitis) in a meta-analysis of 8 trials (N = 194) published through 2011 that were mostly of low quality.88
Other uses
Several studies demonstrated a hepatoprotective effect of propolis in rats against acetaminophen-induced liver injury, as well as injury due to alcohol and carbon-tetrachloride.1, 5, 74 The aqueous and ethanolic extracts appear to be effective by including free-radical scavenging. There are no published human trials to date.
A protective effect against chronic alcohol-induced corneal damage has been demonstrated in rats.75
Dosing
There is limited clinical evidence to support specific dosage recommendations for propolis. Dental preparations containing propolis are commercially available, including oral gels and mouthwashes, despite equivocal results in clinical studies.12
A 13% aqueous solution was used orally in a clinical study in individuals with asthma.66 A 5% preparation was used topically in a study on recurrent vaginitis.25
A study of respiratory tract infection prevention in children used a 50 mg/mL propolis mixture, giving children 1 to 3 years of age 250 mg and children 4 to 5 years of age 375 mg daily for 12 weeks.27 In a small pilot study (N = 18), 20 drops of an ethanolic preparation of Brazilian green propolis taken 3 times a day for 7 days was not effective in eradicating H. pylori, despite in vitro studies suggesting inhibition of bacterial growth.28 Pills containing 300 mg propolis were taken 3 times daily for 12 weeks in patients with type 2 diabetes that improved glycemic and some lipid parameters. (Samadi, 2017)
Pregnancy / Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.76
Interactions
Clinical information is absent. In a study of propolis' effect in mice with Ehrlich carcinoma, an interaction between propolis and bleomycin was noted that resulted in a reduction in survival rate.77, 78
Adverse Reactions
Propolis is considered to be relatively nontoxic.1, 2, 3 Allergic reactions with skin and mucous membrane irritations have been commonly reported in apiary workers79, 80, 81, 82 and a multicenter study reported a prevalence for positive patch tests of 1.9%. Other reports estimate the prevalence to be even higher83; therefore, cautious use in asthmatic or eczematous patients is advised, despite a potentially beneficial clinical trial in patients with asthma.1, 66 Propolis can be added to cosmetic products for its preservative and medicinal properties; a case of eczematous dermatitis on the face after application of honey for cosmetic purposes has also been reported.86 Sensitization to propolis with cross-sensitivity to balsam of Peru, a common additive in flavoring agents, has been reported.82, 84, 85
Adverse reactions are more common at doses greater than 15 g/day2 although a trial using 20 drops of an ethanolic preparation of Brazilian green propolis taken 3 times a day for 7 days resulted in reports of mild nausea and epigastric pain in some participants.28
Toxicology
Information regarding toxicology is lacking. The median lethal dose for mice is estimated to be between 2 to 7.3 g/kg and extrapolated to a safe level in humans of propolis 70 mg/day.3
References
Disclaimer
This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.
This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
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