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Esposito C, Garzarella EU, Bocchino B, et al. A standardized polyphenol mixture extracted from poplar-type propolis for remission of symptoms of uncomplicated upper respiratory tract infection (URTI): a monocentric, randomized, double-blind, placebo-controlled clinical trial. Phytomedicine. 2021;(80):153368.
To evaluate the effects of a standardized oral spray of poplar-type propolis extract (M.E.D. Propolis) on the symptoms of mild upper respiratory tract infections (URTIs)
A monocentric, placebo-controlled, double-blind clinical trial performed in an outpatient setting
This study involved 122 subjects (58 in the propolis group and 64 in the placebo group). The age range was from 18 to 77 years; 54 subjects were male, and 68 were female. All subjects had signs and/or symptoms of a URTI. Subjects were examined by a physician and were eligible for inclusion in the study if they suffered from 1 or more of the following common URTI symptoms: sore throat, muffled dysphonia, and swelling and redness of the throat that began on the same day as the baseline visit (t=0).
The subjects were randomly assigned to receive either a propolis oral spray or a placebo spray from t1 to t3 (5 days). Dose was 2 to 4 sprays 3 times daily. Researchers evaluated each participant at 4 time points: baseline=t0, after 3 days=t1, after 5 days=t2, and at 15 days=t3.
The propolis spray was standardized to contain 15 mg/mL of polyphenols. The spray had a reproducible composition of the 6 major flavonoids found in this type of propolis (ie, galangin, chrysin, pinocembrin, apigenin, pinobanksin, quercetin). Each participant used 2 to 4 sprays 3 times daily for 5 days. The placebo spray had an identical appearance and flavor to the propolis spray.
Study Parameters Assessed
Apart from the primary outcome measure, the researchers evaluated the persistence of positive bacterial throat cultures at t3. They performed throat swabs on all subjects at t0 and then again at t2 and t3 on those subjects who had an initially positive throat culture. At t0, 8 people in the treatment group and 7 people in the placebo group were positive for a bacterial URTI. At t3, none of the subjects in either the treatment or placebo group were found to have a positive bacterial throat culture.
Primary Outcome Measures
The primary outcome measure was the resolution of URTI symptoms. Researchers assessed these symptoms at baseline (t0), 3 days (t1), after 5 days (t2), and at the final timepoint (t3) of the study, 15 days.
At t1, 17% of the participants in the treatment group still had 1 symptom of an URTI. In contrast, about 72% of people in the placebo group still displayed 1 symptom (RR: 2.93, CI: 1.95–4.42).
The results of a univariate analysis showed that only treatment with oral propolis spray was related to the disappearance of symptoms (resolution of all symptoms in the treatment group vs the placebo group: X2=35.57, df=1, P<0.001; resolution from sore throat in the propolis vs placebo group: X2=28.38, df=1, P<0.001; resolution of muffled dysphonia in the propolis vs placebo group: X2=4.38, df=1, P=0.036; and resolution of swelling and redness of the throat in the propolis vs placebo group: X2=16.85, df=1, P<0.001).
Clinicians using natural medicine should not be shy to incorporate propolis into treatment plans for many types of infections.
All logistic models of the data were also significant, showing that the propolis spray was the only variable that correlated with the resolution of all symptoms and single symptoms (all symptoms: X2=46.51, df=7, P<0.001; sore throat: X2=34.21, df=6, P<0.001; swelling and redness of the throat: X2=23.19, df=6, P<0.001; muffled dysphonia: X2=7.87, df=3, P=0.048).
There was no relationship noted between the resolution of symptoms after 3 days and the type of infection (bacterial or viral) or the age or gender of the subjects.
The disappearance of all URTI symptoms occurred 2 days earlier in the propolis group vs the placebo group. Symptoms were gone within 5 days in the placebo group and within 3 days for the treatment group. This finding held true for both viral and bacterial URTIs. Since there were so few bacterial URTIs noted in this study, the authors were not able to make any conclusions related to the effects of propolis on antibiotic-resistant bacteria.
Propolis has always interested me, and it has defied my attempts to categorize it. Is it an herbal medicine? Well, not exactly. It is certainly a “natural medicine.” Propolis is a very complex mixture consisting of polyphenols, wax, resins, pollen, essential oils, minerals, vitamins, and other components. It is created when bees collect plant exudates and mix them with their saliva.1 The bees use propolis to seal their hives, and it has an antimicrobial effect on the hive. The composition of propolis varies based on the type of bees, the time of the year, the plants the bees visit, and other variables.2
Dietrich Klinghardt, MD, recommends the incorporation of Brazilian green propolis into treatment plans for those with Lyme disease accompanied by bartonellosis. Bartonella is a gram-negative, intraerythrocytic bacteria that can be transmitted to humans by ticks and other vectors.3 In my experience, concomitant bartonellosis can make Lyme disease more complex to treat. People with chronic tick-borne diseases need treatment options, and it is nice to know that propolis can be on the menu.
The bad thing about propolis, for the pharmaceutically minded, is that it is such a complex and variable mixture, making the “active compounds” difficult to identify. The good thing about propolis, for those who study and respect natural medicine, is that it is such a complex and variable mixture, with assumed synergies in medicinal compounds. A 2019 review by Przybylek and Karpinski notes that “this diversity of chemical composition gives propolis an additional advantage as an antibacterial agent. The combination of many active ingredients and their presence in various proportions prevents bacterial resistance from occurring.”4 Because of the concerning rise in nosocomial infections from antibiotic-resistant bacteria (especially of the gram-negative variety), there has been a recent focus on the development of “antibiotic hybrids.” These new drugs combine various classes of antibiotics in an attempt to overcome bacterial resistance.5 Perhaps the many constituents in propolis make it the ultimate “antibiotic hybrid?”
Clinicians using natural medicine should not be shy to incorporate propolis into treatment plans for many types of infections. As with many natural medications, propolis has nutrients that can enhance immunity and anti-inflammatory compounds to help deal with the inflammatory nature of infections.6 It has the multifaceted ability to be directly antimicrobial, nourishing, and immune-enhancing all at the same time.7 This is a high bar that would be quite hard for a synthetic drug to reach.
As I continue to review studies on botanical/natural medicine, it appears less common to see a well-designed study on these topics conducted in the United States. This study is no exception. The current study was a collaboration between scientists in Italy and China. There are myriad variables that figure into the equation of the US medical system. One thing is certain though: We spend more on healthcare and have poorer outcomes than other developed nations.8 I can’t help but wonder how much it would benefit us if even a minute fraction of the money that we invest in pharmaceutical research were funneled into investigating natural medications and there were a serious attempt to integrate them into our primary healthcare system. This seems especially true in the age of growing microbial resistance to conventional antibiotics.
I remember being impressed while on a trip to Japan that prescription “Kampo” herbal formulas were readily available at pharmacies. Every pharmacist whom we dropped in on was familiar with Kampo herbal formulas and had a handy Kampo reference book to help them describe to us the composition and effects of these common prescriptions. In Japan, 90% of physicians prescribe Kampo herbal formulas, and the national insurance plan covers them.9
URTIs are the most common reason that people visit doctors worldwide. They result in a cost of $22 billion dollars and cause more than 20 million missed school/work days annually.10 Imagine the suffering that could be averted, and the money that could be saved, by incorporating propolis into the average primary-care URTI visit. This could help patients avoid more complicated URTIs and lessen the need for prescriptions such as steroids and codeine, which have significant side effects. Patients may also be better nourished to ward off the next immunologic assault.
- Esposito C, Garzarella EU, Bocchino B, et al. A standardized polyphenol mixture extracted from poplar-type propolis for remission of symptoms of uncomplicated upper respiratory tract infection (URTI): a monocentric, randomized, double-blind, placebo-controlled clinical trial. Phytomedicine. 2021;(80):153368.
- Przybylek I, Karpinzki TM. Antibacterial properties of propolis. Molecules. 2019;24(11):2047.
- Cheslock MA, Embers ME. Human bartonellosis: an underappreciated public health problem? Trop Med Infect Dis. 2019;4(2):69.
- Przybylek I, Karpinzki TM. Antibacterial properties of propolis. Molecules. 2019; 24 (11):2047.
- Domalaon R, Idowu T, Zhanel GG, Schweizer F. Antibiotic hybrids: the next generation of agents and adjuvants against gram-negative pathogens? Clin Microbiol Rev. 2018;31(2):e00077-17.
- Sforcin JM. Propolis and the immune system: a review. J Ethnopharmacol. 2007;113(1):1-14.
- Wolska K, Gorska A, Antosik K, Lugowska K. Immunomodulatory effects of propolis and its components on basic immune cell functions. Indian J Pharm Sci. 2019;81(4):575-588.
- Tikkanen R, Abrams MK. U.S. health care from a global perspective, 2019: higher spending, worse outcomes? The Commonwealth Fund Web site. https://www.commonwealthfund.org/publications/issue-briefs/2020/jan/us-health-care-global-perspective-2019. Accessed March 6, 2021.
- Kobayashi Y. Kampo medicine in the new model core curriculum of pharmaceutical education. Yakugaku Zasshi. 2016;136(2):423-432. (Article in Japanese.)
- Thomas M, Bomar PA. Upper respiratory tract infection. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021.