Propolis Plus 900 mg by White Heron Pharm

POSSIBLY EFFECTIVE

• Diabetes. Oral propolis seems to improve glycemic control in patients with type 2 diabetes; however, some conflicting evidence exists. Details: A meta-analysis of six clinical trials including 374 patients with type 2 diabetes shows that taking propolis for 8 weeks to 6 months reduces glycated hemoglobin (HbA1c) by 0.5% and fasting plasma glucose by 14 mg/dL when compared with placebo. However, significant improvements in insulin levels or measures of insulin resistance were lacking (102520). While this pooled analysis suggests that propolis is modestly effective for improving glycemic control, individual study results are mixed. Three of the trials in the analysis failed to demonstrate significant improvements in HbA1c or glucose levels; however, all of these studies were small and likely underpowered to detect meaningful improvements in glycemic control (102523,102524,102525). Other studies showed positive results, with reductions in HbA1c ranging from 0.9% to 1.1% and reductions in fasting plasma glucose ranging from 21 mg/dL to 26 mg/dL. The doses and durations of propolis therapy in these studies included 400 mg daily for 6 months (99173), 900 mg daily for 12 weeks (95883), and 500 mg three times daily for 8 weeks (102521).
• Herpes labialis (cold sores). Topical propolis ointment or cream, applied five times daily, may improve lesion healing and reduce symptoms in patients with cold sores. Details: One small clinical study in patients with cold sores shows that applying a specific propolis 3% ointment (Herstat or ColdSore-FX by Afexa), five times daily at the start of symptoms, reduces cold sore duration by about 3-4 days and may reduce cold sore-related pain when compared with placebo (17664,17665). Larger clinical studies in patients with cold sores in the papular or vesicular stages show that applying a lip cream containing a specific propolis extract (GH2002) 0.5% five times daily for 5-10 days reduces the time to complete encrustation/epithelialization by about 1 day and improves symptoms of pain, burning, itching, tension, and swelling when compared with acyclovir 5% cream (95875,102519).
• Oral mucositis. Most clinical research shows that oral propolis or propolis-containing mouthwash can reduce the risk for severe, chemotherapy-induced oral mucositis. Details: A meta-analysis of five clinical trials including 209 patients shows that using mouthwash containing propolis reduces the odds of severe chemotherapy-induced oral mucositis by 65% when compared with placebo in cancer patients (99171). Rinsing with 5-10 mL of a propolis mouth rinse for 1 minute three times daily, alone or in addition to chlorhexidine mouthwash and fluconazole for 7-14 days, improves mucositis and redness when compared to control in patients receiving chemotherapy (92793,95877). A small clinical study in patients receiving chemotherapy for breast cancer also shows that taking tablets of propolis (Natur Farma S.A.S.) 80 mg two or three times daily for 3 weeks, in addition to rinsing with sodium bicarbonate solution, decreases the development of mucositis when compared with only rinsing with sodium bicarbonate solution (95882). However, at least one high quality clinical study shows that rinsing with 7 mL of a specific product (Faringel, Cadigroup) containing propolis extract 6% and other ingredients three times daily for 6 weeks does not prevent the development of mucositis due to chemotherapy when compared with placebo in patients with head and neck cancer (95879).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. It is unclear if oral propolis is beneficial for improving athletic performance. Details: A small clinical study in healthy male military cadets shows that taking propolis 450 mg twice daily for 4 weeks does not improve measures of aerobic or anaerobic performance during exercise testing when compared with placebo (108519).
• Atopic disease. It is unclear if oral propolis can prevent atopic disease in lactating adults or their infants. Details: A small clinical study in lactating adults shows that taking propolis 300 mg daily for 4-10 months does not appear to reduce the risk for developing atopic disease in either the mothers or their infants when compared with placebo (102518). However, due to the small sample size, this study may have been inadequately powered to detect a difference between groups.
• Breast cancer. It is unclear if oral propolis is beneficial in patients with breast cancer. Details: A small clinical study in patients with stage II or III breast cancer receiving chemotherapy shows that taking propolis 250 mg twice daily for 3 months improves quality of life and nutritional status when compared with placebo (108518). It is unknown if propolis can increase the likelihood of survival or remission in patients with breast cancer.
• Burns. It is unclear if topical propolis is beneficial in patients with minor burns. Details: One small clinical study in patients with minor burns shows that application of propolis cream to burn wounds every 3 days improves healing and reduces inflammation when compared with silver sulfadiazine. Propolis cream seems to be as effective for preventing infection as silver sulfadiazine in these patients (8663).
• Canker sores. It is unclear if oral propolis is beneficial in patients with canker sores. Details: A very small clinical study in patients with recurrent canker sores shows that taking propolis 500 mg daily for 6-13 months significantly reduces canker sore outbreaks and improves quality of life when compared with placebo. A 50% or greater reduction in cold sore outbreaks was reported in 60% and 11% of patients taking propolis or placebo, respectively (17629).
• Catheter-related infections. It is unclear if topical propolis is beneficial for the prevention of catheter-related infections. Details: One small clinical study in patients with peritoneal dialysis catheters shows that cleaning the exit site after dialysis with a normal saline wash and propolis 10% ointment for 6 months does not reduce the rate of catheter site infections when compared with using normal saline wash plus mupirocin 2% ointment or normal saline wash alone (109985).
• Chronic kidney disease (CKD). It is unclear if oral propolis is beneficial in patients with CKD. Details: A small clinical study in patients with CKD shows that taking Brazilian green propolis extract (EPP-AF) 250 mg twice daily for 12 months reduces proteinuria, but does not increase estimated glomerular filtration rate (eGFR), when compared with placebo (105785).
• Chronic obstructive pulmonary disease (COPD). Oral propolis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with frequent exacerbations of COPD shows that taking a combination of N-acetylcysteine (NAC) 1200 mg and propolis 160 mg orally once daily for 3 months reduces the incidence of acute exacerbations during 1 year of follow-up when compared with placebo or a lower dose combination of NAC 600mg and propolis 80 mg (109984). Further research shows that using the higher dose combination for 6 months reduces acute exacerbations, cough, and overall COPD severity, and increases dyspnea-free walking distance, when compared with placebo or the lower dose combination (109986).
• Common cold. It is unclear if oral propolis is beneficial in patients with the common cold. Details: One small clinical study in patients with rhinovirus infection shows that taking propolis (dose and duration unknown) might decrease the duration of cold symptoms 2.5-fold when compared with placebo (6602).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral propolis is beneficial for the prevention or treatment of COVID-19. Details: A small observational study in healthcare professionals working in an emergency department shows that taking a 30% Anatolian propolis solution as 20 drops twice daily for one month reduces the occurrence of COVID-19 positivity to 2 of 102 subjects, compared with 14 of 102 in an untreated control group (109983). The validity of this study is limited by the lack of blinding and randomization. A small, open-label clinical study in hospitalized adults with COVID-19 shows that taking a standardized green propolis extract (EPP-AF) 100 mg or 200 mg four times daily for 7 days, along with conventional therapy, reduces length of hospital stay by around 5-6 days, but does not affect the need for supplemental oxygen, odds of intubation, or admission to the intensive care unit, when compared with conventional therapy alone (108514).
• Dengue fever. It is unclear if oral propolis is beneficial in patients with dengue fever. Details: A small clinical study in patients with dengue hemorrhagic fever shows that taking propolis extract (Propoelix) 400 mg three times daily for 7 days reduces the length of hospital stay by about 18 hours when compared with placebo. This was based on being deemed technically fit for discharge because of a recovery of platelet counts. The effect of propolis on other symptoms of dengue fever was not investigated in this study (99168).
• Dental caries. It is unclear if topical propolis, used either as a chewing gum or mouthwash, can prevent dental caries in children. Details: One small clinical trial in children 6-8 years of age at high risk of dental caries shows that chewing propolis gum twice daily for 20 minutes or rinsing with 10 mL of propolis 2% mouthwash for 1 minute twice daily for 2 weeks reduces plaque and Streptococcus mutans count when compared to baseline. There were no differences between the two propolis formulations; however, children preferred the chewing gum over the mouthwash (105790). The validity of these findings is limited by a lack of control group.
• Denture stomatitis. Small clinical studies suggest that topical propolis may speed recovery in patients with denture stomatitis. Details: One very small clinical study in denture-bearing patients with prosthesis stomatitis candidiasis shows that applying Brazilian green propolis 20% ethanol extract topically four times daily for 7 days can cause regression of candidiasis lesions. After 7 days, 58% of patients treated with propolis and 67% of patients treated with nystatin had total lesion remission. After 15 days, all patients in both groups saw total lesion remission (70070). Also, two small clinical studies in patients with denture-induced oral mucositis show that applying propolis 2% to 3% gel (EPP-AF) to dentures three to four times daily for 7-14 days improves the cure rate and reduces erythema. In these studies, propolis appeared to be comparable to applying miconazole to dentures (95881,95884).
• Depression. It is unclear if oral propolis is beneficial as adjunct therapy in patients with depression. Details: A small clinical study in patients with moderate to severe depression inadequately managed with selective serotonin reuptake inhibitors (SSRIs) shows that taking propolis 1000 mg daily for 6 weeks, in addition to SSRI therapy, reduces symptoms of depression, as measured on the 17-item Hamilton Depression Scale (HAMD-17) and Beck Depression Inventory (BDI), when compared with placebo (108523).
• Diabetic foot ulcers. It is unclear if topical propolis is beneficial in patients with diabetic foot ulcers. Details: A small clinical study in patients with diabetic foot ulcers shows that topical application of propolis 5% ointment in addition to routine care for 4 weeks reduces ulcer size about 2.5-fold more than routine care alone (99172).
• Genital herpes. It is unclear if topical propolis is beneficial in patients with genital herpes. Details: A small clinical study in patients with recurrent genital herpes caused by herpes simplex virus type 2 (HSV-2) shows that applying propolis 3% ointment (Herstat or ColdSore-FX by Afexa) four times daily for 10 days reduces healing time and increases the relative rate of complete healing by 1.7- and 2-fold when compared with acyclovir 5% ointment and placebo, respectively (1926).
• Gingivitis. Small clinical studies suggest that topical propolis may modestly improve symptoms in patients with gingivitis. Details: A small clinical study shows that rinsing with a propolis 2% solution 20 mL twice daily for 21 days is as effective as a rinse containing sodium fluoride 0.05% plus cetylpyridinium chloride 0.05% for the prevention of induced gingival redness and bleeding (99169). Another small clinical study in patients with gingivitis shows that rinsing with a propolis solution twice daily for 4 weeks reduces gingival bleeding, but does not improve plaque index, when compared with placebo (108513). Propolis has also been evaluated in combination with other ingredients. One small clinical study in patients with plaque-induced gingivitis shows that adjuvant therapy with a topical gel containing propolis and other ingredients (Oralsan NBF gel, IDS SpA) for 15 days following scaling and root planing is as effective as a chlorhexidine-based gel for improving bleeding, plaque, and probing depth (99170). Another small clinical study in patients with generalized or localized gingivitis or stage I periodontitis shows that taking 194 mg of a product containing propolis and mangosteen improves the modified gingival index by 31% or 40% at weeks 4 or 8, respectively, compared with 16% or 25% in those receiving placebo. No changes in probing depth, clinical attachment, plaque index, bleeding, or gingival recession were observed (106789).
• Helicobacter pylori. It is unclear if oral propolis is beneficial in patients with H. pylori infection. Details: One very small, uncontrolled clinical study in patients with H. pylori infection shows that taking 60 drops of an alcoholic preparation of Brazilian green propolis daily for 7 days does not reduce H. pylori infection when compared to baseline (70107).
• HIV/AIDS. Although there has been interest in using oral propolis as an adjunct to antiretroviral therapy for HIV/AIDS, there is insufficient reliable information about the clinical effects of propolis for this purpose.
• Intestinal parasite infection. It is unclear if oral propolis is beneficial in patients with giardiasis. Details: One small clinical study in adults with giardia infection shows that taking a specific propolis 30% extract (Propolisina, Apis Flora) for 5 days increases cure rates when compared with tinidazole. The cure rate was 60% with propolis extract, compared to only 40% with tinidazole. In children with giardiasis, taking propolis 10% extract showed a 52% cure rate; however, the rate of cure with tinidazole was not available (70121).
• Malnutrition. It is unclear if oral red propolis is beneficial in malnourished children with frequent respiratory tract infections. Details: A small clinical study in children aged 1-5 years with frequent respiratory tract infections and growth failure associated with malnutrition shows that giving 3% red propolis in 8 mL (10 grams) of honey once daily in addition to adequate nutrition does not improve weight gain or reduce the frequency of respiratory infections when compared with honey plus adequate nutrition (109987).
• Muscle fatigue. It is unclear if oral propolis is beneficial for speeding recovery from muscle fatigue. Details: One small study in young, healthy males shows that taking Brazilian green propolis 1575 mg before meals three times daily for one week, followed by exercise to induce muscle fatigue, reduces the time to regain maximal contraction torque after stopping when compared with placebo or a 100-mg dose of propolis. There was no difference in average peak power between the groups (109989).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral propolis is beneficial in patients with NAFLD. Details: One small clinical study in patients with NAFLD shows that taking propolis extract 250 mg twice daily for 4 months improves markers of hepatic steatosis and fibrosis, but does not improve liver function, when compared with placebo (105786). Another small study in adults with obesity and NAFLD shows that taking propolis 510 mg daily for 8 weeks with a calorie-restricted diet reduces liver fibrosis, fasting blood glucose levels, serum insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) when compared with placebo. However, it does not affect the severity of fatty liver, anthropometric measurements, lipid profile, or levels of inflammatory markers (109988).
• Peptic ulcers. Although there has been interest in using oral propolis for peptic ulcers, there is insufficient reliable information about the clinical effects of propolis for this purpose.
• Periodontitis. It is unclear if oral propolis or propolis extract rinse is beneficial in patients with periodontitis. Details: One small clinical study in patients with type 2 diabetes and chronic periodontitis also receiving scaling and root planing shows that taking propolis 400 mg daily for 6 months reduces probing depth and improves clinical attachment by a small amount when compared with scaling and planing alone. There was no additional benefit with propolis on measures of gingivitis, plaque, or bleeding when compared with scaling and planing alone (99173). Another very small clinical study in patients with chronic periodontitis shows that irrigation of the gums with an ethanol solution containing propolis extract 20% twice weekly for 2 weeks reduces gum bleeding when compared with irrigation with ethanol 14% solution (95876). Propolis has also been evaluated in combination with other ingredients. A small clinical study in patients with generalized or localized gingivitis or stage I periodontitis shows that taking 194 mg of a product containing propolis and mangosteen improves the modified gingival index by 31% or 40% at weeks 4 or 8, respectively, compared with 16% or 25% in those receiving placebo. No changes in probing depth, clinical attachment, plaque index, bleeding, or gingival recession were observed (106789).
• Rheumatoid arthritis (RA). It is unclear if oral propolis is beneficial in patients with RA. Details: A small clinical study in females with RA shows that taking Brazilian propolis 508.5 mg daily for 24 weeks does not improve measures of disease activity, quality of life, or activities of daily living when compared with placebo (108515).
• Sepsis. It is unclear if oral propolis is beneficial in patients with sepsis. Details: A small clinical study in patients with pneumosepsis shows that taking propolis 1000 mg daily along with conventional therapy does not improve survival rates or disease severity, as measured using APACHE II and SOFA scores, when compared with placebo. The combination of propolis 1000 mg plus melatonin 20 mg daily did improve disease severity scores but had no effect on survival (108524).
• Tinea pedis. It is unclear if topical propolis is beneficial in patients with tinea pedis. Details: A case series involving students with athlete's foot found that topical treatment with a 100 mg/mL ethanolic extract of Brazilian green propolis results in less skin itching, peeling, and redness when compared with petroleum jelly placebo, but not when compared with miconazole (95880).
• Tuberculosis. Although there has been interest in using oral propolis for tuberculosis, there is insufficient reliable information about the clinical effects of propolis for this purpose.
• Upper respiratory tract infection (URTI). It is unclear if oral propolis spray is beneficial in patients with URTI. Details: One small clinical study in patients reporting mild URTI symptoms shows that use of a propolis oral spray (M.E.D. Propolis, B Natural srl), 2-4 sprays daily, providing 6 mg of polyphenols per spray, for 5 days reduces the time to complete resolution of symptoms by 2 days when compared with placebo (105787). Propolis has also been evaluated in combination with other ingredients. A large clinical study in children 1-5 years of age shows that taking 5-7.5 mL of a specific combination product (Chizukit, Hadas Corp Ltd.) containing propolis 50 mg/mL, echinacea extract 50 mg/mL, and vitamin C 10 mg/mL for 12 weeks reduces the number of children who experience one or more upper respiratory tract illnesses, as well as the number and duration of illnesses, when compared with placebo (48551). It is unclear if these findings are due to propolis, other ingredients, or the combination.
• Urinary tract infections (UTIs). Oral propolis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 3 small clinical studies in adults with uncomplicated UTIs shows that taking combination products containing propolis, Hibiscus sabdariffa, and gelatin or xyloglucan daily for 5-10 days, then daily for two weeks each month for two months, reduces the odds of UTI recurrence by 87% when compared with control (108520). One of these studies used a specific product (Utipro Plus, Noventure) containing propolis 100 mg, xyloglucan extract 100 mg, Hibiscus sabdariffa extract 100 mg, and gelatin 50 mg once daily for 15 consecutive days each month for 6 months (101734). A small clinical study in females with recurrent UTIs shows that taking two capsules of a specific combination product (DUAB, Nutrivercell) containing propolis, cranberry, and zinc daily for 6 months reduces the number of recurrent UTIs by around 0.8 and delays the time to first recurrent UTI by around 26 days when compared with placebo (102522).
• Vaginitis. It is unclear if topical propolis is beneficial in patients with vaginitis. Details: A small clinical study in patients with chronic vaginitis shows that applying 50 mL of a specific aqueous solution containing propolis 5% (Melprotect, Melbrosin International) to the vagina for 7 days can reduce symptoms and improve quality of life when compared to baseline (70068). The validity of these findings is limited by a lack of control group.
• Warts. It is unclear if oral propolis is beneficial in patients with warts. Details: One small clinical study in adults and children with common and plane warts shows that taking propolis (Bee Propolis, Pollen) 500 mg orally daily for up to 3 months increases wart cure rates when compared with echinacea or placebo. Common warts were cured in 73% of patients taking propolis, compared to 20% taking echinacea and 8% taking placebo. Plane warts were cured in 75% of patients taking propolis, compared with 36% taking echinacea and 21% taking placebo. Neither propolis nor echinacea were effective for treating plantar warts (92800).
• Wound healing. It is unclear if topical propolis or propolis mouth rinse improves wound healing. Details: One small clinical study shows that using an aqueous alcohol mouth rinse containing propolis 5% five times daily for 1 week following sulcoplasty improves healing and reduces pain and inflammation (799). Another small clinical study in males recovering from surgery for sacrococcygeal pilonidal disease shows that using 1 mL of propolis 15% solution on the wound dressing daily for 28 days accelerates wound healing when compared with normal saline (108516) However, another small clinical trial in patients undergoing dental surgery shows that using a propolis 20% solution in a dressing is no more effective than the dressing alone for improving wound healing and reducing pain associated with the wound (99167). More evidence is needed to rate propolis for these uses.

(Read more about PROPOLIS)

POSSIBLY INEFFECTIVE

• Bladder cancer. Consuming tomatoes and tomato-based products does not appear to reduce the risk of bladder cancer. Details: Observational studies have found no association between tomato and tomato-based product intake and the risk of bladder cancer (2407).
• Breast cancer. Consuming tomatoes and tomato-based products does not appear to reduce the risk of breast cancer. Details: Observational studies have found no association between tomato or tomato-based product intake and risk of breast cancer (15747).
• Diabetes. Consuming tomatoes and tomato-based products does not appear to prevent the development of type 2 diabetes or improve glycemic control in patients with type 2 diabetes. Details: Observational studies have found that increasing intake of tomato or tomato-based products does not significantly decrease the risk of developing type 2 diabetes (14004,14361). Additionally, a small clinical study in non-smoking male patients with type 2 diabetes shows that consuming raw tomato 200 grams daily for 8 weeks does not improve plasma glucose levels when compared to baseline (102477). The validity of this finding is limited by the lack of comparator group.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. It is unclear if tomato improves skin appearance. Details: A small study of females aged 35-55 shows that taking a certain tomato pulp product (Lumenato, Lycored) 1 capsule daily for 12 weeks improves patient reported skin appearance scores when compared to baseline (110523). The interpretation of this result is limited by the lack of a placebo group.
• Benign prostatic hyperplasia (BPH). Oral tomato powder has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with BPH shows that taking 5 grams of a whole tomato food supplement consisting of tomato powder and polyphenols extracted from olives daily for 2 months improves quality of life and reduces lower urinary tract symptoms including urinary frequency, urinary urgency, and nocturia when compared to baseline. No improvements in these symptoms were reported with placebo (106656). It is unclear if these findings are due to tomato, olive polyphenols, or the combination.
• Cardiovascular disease (CVD). It is unclear if consuming tomato-based foods reduces the risk of cardiovascular events. Details: Observational research has found that increased consumption of tomato-based foods is associated with an insignificant trend towards a reduced risk of myocardial infarction, stroke, and other cardiovascular events (10418,102178).
• Cataracts. It is unclear if consuming tomatoes reduces the risk of cataracts. Details: Observational research has found that eating more than 3 servings of tomatoes each week may decrease the risk of developing cataracts (9439).
• Cervical cancer. It is unclear if consuming tomatoes reduces the risk of cervical cancer. Details: Observational research has found that increased tomato intake is associated with a decreased risk of cervical cancer (2407).
• Colorectal cancer. Research on the benefits of consuming tomatoes or tomato-based products for the prevention of colorectal cancer is conflicting and limited to observational studies only. Details: Some observational research has found that increasing tomato or tomato-based product intake is associated with a reduced risk of colorectal cancer (2404,2407). However, higher quality observational research has found that tomato-based product intake is not associated with risk of colorectal cancer (15747).
• Exercise-induced asthma. It is unclear if oral tomato extract is beneficial in patients with exercise-induced asthma. Details: A small clinical study in patients with exercise-induced asthma shows that taking a specific tomato extract (Lyc-O-Mato, LycoRed Ltd) 30 mg daily for 1 week seems to reduce exercise-induced asthma when compared with placebo. The tomato extract seems to prevent decreases in forced expiratory volume (FEV1) in response to exercise (7898).
• Gastric cancer. Research on the benefits of consuming tomatoes or tomato-based products for the prevention of gastric cancer is conflicting and limited to observational studies only. Details: Some observational studies have found that increasing tomato or tomato-based product intake is associated with a reduced risk of gastric cancer in some subgroups of patients (2407,15747,102480). However, other observational research has found that tomato-based product intake is not associated with risk of gastric cancer (15747). In 2005, the US Food and Drug Administration (FDA) approved a qualified health claim regarding tomatoes and gastric cancer risk. However, the FDA concludes that it is highly unlikely that tomatoes reduce the risk of gastric cancer (102375).
• Hyperlipidemia. Small clinical studies suggest that consuming tomato sauce or semi-dried tomatoes may modestly reduce low-density lipoprotein (LDL) cholesterol levels in patients with hyperlipidemia. Details: One small, open-label clinical trial in patients with hyperlipidemia shows that consuming a specific vine-ripened tomato sauce (OsteoCol, C.G. Food, SRL) 150 mL daily for 6 weeks reduces total cholesterol and LDL cholesterol levels when compared to baseline. Patients adherent to the tomato sauce regimen showed an 11 mg/dL and 12 mg/dL reduction in total and LDL cholesterol, respectively, while those consuming a sterol-enriched yogurt saw total and LDL cholesterol levels decrease by 18 mg/dL and 16 mg/dL, respectively. Patients with a baseline LDL cholesterol level of greater than 152 mg/dL saw the greatest benefit from this tomato sauce (106653). Another small clinical study in Japanese patients with borderline high cholesterol shows that taking 50 grams of a semi-dried tomato containing lycopene 22-27.8 mg daily for 12 weeks modestly reduces LDL cholesterol levels but does not affect high-density lipoprotein (HDL) cholesterol levels when compared with taking 50 grams of a tomato without lycopene (102180). This suggests that any benefit of tomato on blood lipid levels is likely due to its lycopene content.
• Hypertension. Small clinical studies and observational research suggest that oral tomato extract or dietary tomato consumption may modestly reduce blood pressure in patients with hypertension. Details: Several small clinical trials in patients with hypertension show that taking a specific tomato extract product (Lyc-O-Mato, LycoRed, Ltd.), providing lycopene 15-30 mg daily, for 6-8 weeks, reduces systolic blood pressure by around 7-13 mmHg and diastolic blood pressure by around 4-6 mmHg when compared to baseline (14287,60415,102182). The validity of these findings is limited by the lack of a comparator group. Additionally, a large observational study, conducted over 3 years, suggests that moderate consumption of tomato-based products (i.e., 44-82 grams daily) is associated with marginally lower blood pressure when compared with higher and lower consumption in older adults with grade 1 hypertension. However, this association is not seen in patients with grade 2 or 3 hypertension (113145). Interpretation of these results is limited by self-reported data and lack of generalizability outside of confounders relating to a Mediterranean lifestyle. Evidence on the use of tomato in patients with pre-hypertension is mixed. One small clinical study in patients with pre-hypertension shows that taking a specific tomato extract (Fruitflow, Provexis Plc, UK.) 150 mg as a single dose seems to modestly reduce blood pressure over a 24-hour period when compared with placebo (102478). This study is limited by its small size and short duration. Another small clinical study in pre-hypertensive patients shows that taking a specific tomato extract (Lyc-o-Mato, LycoRed Ltd) containing lycopene 15 mg daily for 8 weeks does not reduce blood pressure when compared with placebo (42079). The impact of dietary tomato consumption on preventing hypertension has also been evaluated. A large prospective observational study in Chinese adults without a history of smoking or myocardial infarction suggests moderate dietary intake of tomatoes (i.e. up to 33.3 grams daily) is associated with a 49-58% reduction in the risk of developing new onset hypertension when compared with no consumption after about 6 years' follow up. However, the associated risk reduction was less with higher consumption (110525). These results may not apply to patients in countries where dietary trends are different, and the validity of these findings is limited by the potential for confounding. Another large observational study, conducted over 3 years in older adults at high cardiovascular risk, suggests that higher consumption (i.e., at least 1 large-sized tomato daily) is associated with reduced risk of hypertension by 36% when compared with moderate and lower consumption (113145). However, interpretation of these results is limited by self-reported data, and lack of generalizability outside of confounders relating to a Mediterranean lifestyle.
• Lung cancer. It is unclear if consuming tomatoes reduces the risk of lung cancer; the available research is conflicting. Details: Some observational studies have found an association between increased tomato and tomato-based product consumption and a reduced risk of lung cancer; however, many of these studies were not stratified based on the patient's smoking status. Higher quality, large-scale observational studies have not found any association between tomato product intake and lung cancer risk (15747).
• Muscle strength. It is unclear if consuming tomatoes improves muscle strength or attenuates declines in muscle strength. Details: A small observational study in Japanese adults 22-68 years of age found that more frequent tomato consumption (2 or more times weekly) is associated with an attenuated rate of handgrip strength decline over 3 years when compared with less frequent tomato consumption (102473).
• Ovarian cancer. Research on the benefits of consuming tomatoes or tomato-based products for the prevention of ovarian cancer is conflicting and limited to observational studies only. Details: Some observational research has found that increased tomato or tomato juice intake is not associated with risk of ovarian cancer; however, consuming tomato sauce two or more times weekly is associated with a decreased risk (2407). Other observational research has found that increased dietary intake of lycopene, particularly from tomato sauce, is associated with a reduced risk of ovarian cancer in premenopausal patients (10133). In 2005, the US Food and Drug Administration (FDA) approved a qualified health claim regarding tomato sauce and ovarian cancer risk. However, the FDA concludes that it is highly uncertain that tomato sauce reduces the risk of ovarian cancer (102375).
• Pancreatic cancer. Research on the benefits of consuming tomatoes or tomato-based products for the prevention of pancreatic cancer is conflicting and limited to observational studies only. Details: A large-scale observational study have found that that tomato or tomato-based product intake is not associated with a decreased risk of pancreatic cancer (15747). However, other observational studies have found that raw tomato intake, and high tomato intake in general, is associated with a reduced risk of pancreatic cancer (2407,15747,15750). In 2005, the US Food and Drug Administration (FDA) approved a qualified health claim regarding tomatoes and pancreatic cancer risk. However, the FDA concludes that it is highly unlikely that tomatoes reduce the risk of pancreatic cancer (102375).
• Prostate cancer. Consuming tomatoes or tomato-based products may slightly lower the risk of prostate cancer; however, observational research is mixed and high-quality clinical trials addressing tomato intake and prostate cancer risk are lacking. Details: Some observational studies have found that consuming tomato products, including tomatoes, tomato sauce, pizza, or tomato juice, one time or more per week, is associated with a modest reduction in the risk of prostate cancer (2406,7772,7895,12878,15747,102476). However, other observational research has found that tomato consumption is not associated with a reduced risk of prostate cancer (14125,15172,15747,92171). One small clinical study in patients with high-grade prostatic intraepithelial neoplasia shows that taking tomato extract capsules containing lycopene 30 mg daily for 6 months does not impact benign tissue endpoints when compared with placebo (102471). In 2005, the US Food and Drug Administration (FDA) approved a qualified health claim stating that one-half to one cup of tomatoes or tomato sauce weekly may reduce the risk of prostate cancer. However, the FDA concludes that there is little scientific evidence to support this claim (102375).
• Radiation dermatitis. It is unclear if drinking tomato juice is beneficial in patients with radiation dermatitis. Details: One small, uncontrolled clinical trial in patients undergoing radiotherapy for breast cancer shows that drinking tomato juice 160 mg daily for 6 months after radiotherapy improves the severity of dermatitis within 1 month of treatment when compared to baseline (106654). The lack of a comparator group limits the validity of these findings; it is unclear how tomato juice consumption compared with the natural resolution of radiation dermatitis. More evidence is needed to rate tomato for these uses.

(Read more about TOMATO)

POSSIBLY SAFE ...when used orally and appropriately. Propolis has been used with apparent safety in clinical research at doses of up to 1500 mg daily (95883,99173,102520,102521). ...when used topically. Propolis as a 3% or 10% ointment, 0.5% cream, 30% mouth rinse, or 15% solution has been used with apparent safety in small clinical studies (799,1926,6602,8663,17629,17664,17665,92793,92800,95882)(99171,99173,102519,102521,105785,105786,108516,108523,109985).

PREGNANCY:
Insufficient reliable information available; avoid using.

LACTATION: POSSIBLY SAFE
when used orally and appropriately during lactation. Propolis 300 mg daily has been used for 4-10 months in one clinical study with no apparent adverse effects to nursing infants (102518).

(Read more about PROPOLIS)

LIKELY SAFE ...when the ripe or unripe tomato fruit or its products are consumed in amounts found in foods (2406,9439,10418,106653,106654). ...when tomato leaf is consumed in regular food amounts (18).

POSSIBLY SAFE ...when a tomato extract is used orally for medicinal purposes. A specific tomato extract (Lyc-O-Mato, LycoRed Ltd) has been used with apparent safety in clinical studies lasting up to 8 weeks (7898,14287,102182).

POSSIBLY UNSAFE ...when the tomato leaf or unripe green tomato fruit is used orally in excessive amounts. Tomato leaf and unripe green tomatoes contain tomatine, which has been associated with toxicity when consumed in large quantities (18,102957). There is insufficient reliable information available about the safety of the tomato vine.

PREGNANCY AND LACTATION: LIKELY SAFE
when the tomato fruit or its products are consumed in typical food amounts. There is insufficient reliable information available about the safety of tomato extracts when used during pregnancy or lactation; avoid using.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, propolis might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.  Details In vitro research shows that propolis water extract and the propolis constituent, caffeic acid phenethyl ester, can inhibit platelet aggregation (50794,95885). Additionally, evidence from an animal model shows that taking propolis in addition to warfarin decreases INR, suggesting that propolis can decrease the effectiveness of warfarin (95874).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP1A2.  Details In vitro research shows that propolis extract can inhibit CYP1A2 (92797,92799). However, animal research shows that propolis extract does not significantly affect CYP1A2 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that inhibit CYP1A2 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect (92797). This effect has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP2C19.  Details In vitro research shows that propolis extract can inhibit CYP2C19 (92797,92799). However, animal research shows that propolis extract does not significantly affect CYP2C19 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that inhibit CYP2C19 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect (92797). This effect has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP2C9.  Details In vitro research shows that propolis extract can inhibit CYP2C9 (92797,92799). However, animal research shows that propolis extract does not significantly affect CYP2C9 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that inhibit CYP2C9 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect (92797). This effect has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP2D6.  Details In vitro research shows that propolis extract can inhibit CYP2D6 (92797,92799). However, animal research shows that propolis extract does not significantly affect CYP2D6 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that inhibit CYP2D6 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect (92797). This effect has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, propolis might increase levels of drugs metabolized by CYP2E1.  Details In vitro research shows that propolis can inhibit CYP2E1 (92799). This effect has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of propolis might increase blood levels of drugs metabolized by CYP3A4.  Details Some in vitro research shows that propolis extract can inhibit CYP3A4 (92797); however, other in vitro research shows that propolis has no effect on CYP3A4 activity (92799). Furthermore, animal research shows that propolis extract does not significantly affect CYP3A4 activity when administered to rats at doses up to 250 mg/kg. It is postulated that the constituents of propolis that might in inhibit CYP3A4 in vitro do not have significant effects in vivo due to low bioavailability and hepatic first-pass effect (92797). This effect has not been reported in humans.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, propolis might decrease the effectiveness of warfarin.  Details Animal research shows that taking propolis in addition to warfarin decreases the international normalized ratio (INR) (95874). This effect has not been reported in humans.

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General ...Orally and topically, propolis seems to be well tolerated.
Most Common Adverse Effects:
Orally: Headache.
Topically: Contact cheilitis and contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions in sensitive individuals.

Dermatologic ...Propolis can cause allergic reactions and acute oral mucositis with ulceration from the use of the propolis-containing lozenges (2632).
Topically, propolis-containing products, including some cosmetics, can cause eczematous contact dermatitis, erythema multiforme-like contact dermatitis, or allergic contact cheilitis (2632,15647,92796,92798,95878,95882,102517).
Patients allergic to bees or bee products may be more likely to experience allergic reactions to propolis.

Genitourinary ...Vulvar eczema caused by propolis sensitization after topical therapy has been reported (70067).

Hepatic ...Orally, propolis may cause an increase in liver enzymes when used long-term at high doses. In one case, a 30-year-old male presented with persistent abnormal liver enzymes for six months. With other causes ruled out, the patient disclosed using more than 10 propolis lozenges per day for several months to treat a sore throat. Upon discontinuation of the propolis lozenges, liver enzymes returned to normal (105788). Despite concerns presented in this case, analyses of small clinical studies suggest that propolis may have hepatoprotective effects when used at doses of 500-1000 mg daily for up to one year (108521,108522).

Immunologic ...In one case report, a 36-year-old female developed severe erythematous papules and patches with edema of the face, neck, arms, abdomen, and thighs after consuming propolis solution for a few weeks. After symptom resolution, a patch test showed an extreme positive reaction to propolis (106443). In another case, laryngeal edema and severe anaphylactic reaction has been reported in a patient who used topical propolis for the treatment of acute pharyngitis. The patient died due to complications of hypoxia that resulted from the allergic reaction (70063).
Topically, propolis-containing products can cause allergic contact dermatitis, including cheilitis, when used on or near the lips or mouth (15647,92796,92798,102517). Propolis-containing lozenges can cause allergic reactions as well as acute oral mucositis with ulceration (2632).
Patients allergic to bees or bee products may be more likely to experience allergic reactions to propolis.

Neurologic/CNS ...Orally, propolis may cause headache in some patients. In one clinical trial, around 7% of patients taking propolis 250 mg twice daily for 4 months reported mild headache (105786).

Renal ...In one case report, a 59-year-old male with cholangiocarcinoma developed acute kidney failure requiring hemodialysis after taking a Brazilian preparation of propolis 5 mL three times daily for 2 weeks. Renal function improved when propolis was discontinued. The patient restarted taking propolis and symptoms developed again and the patient again required hemodialysis. Symptoms of renal failure improved when propolis was finally discontinued. This product was not screened for contaminants; however, family members of this patient used the same product without apparent adverse effects (14300).

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General ...Orally, tomato leaves and ripe or unripe tomato fruit are well tolerated in typical food amounts. Tomato extracts also seem to be well tolerated. Tomatine, a glycoalkaloid found in tomato leaves and unripe green tomatoes, can cause serious side effects when consumed in excessive amounts.
Serious Adverse Effects (Rare):
Orally: Bradycardia, diarrhea, respiratory disturbances, spasms, vomiting, and death with excessive consumption of tomatine, a glycoalkaloid found in tomato leaves and unripe green tomatoes.

Cardiovascular ...Orally, the glycoalkaloid tomatine in tomato leaf or green tomatoes can cause bradycardia when consumed in excessive amounts (18,102957).

Gastrointestinal ...Orally, the glycoalkaloid tomatine in tomato leaf or green tomatoes can cause severe mucous membrane irritation, vomiting, diarrhea, and colic when consumed in excessive amounts (18,102957).

Immunologic ...In a case report, a 31-year-old female working in the supermarket developed an airborne allergy to tomato stem proteins with symptoms of severe rhinoconjunctivitis. This woman did not have a food allergy to tomato fruit (102467).

Neurologic/CNS ...Orally, the glycoalkaloid tomatine in tomato leaf or green tomatoes can cause dizziness, stupor, headache, and mild spasms when consumed in excessive amounts (18,102957).

Pulmonary/Respiratory ...Orally, the glycoalkaloid tomatine in tomato leaf or green tomatoes can cause respiratory disturbances when consumed in excessive amounts. In severe cases, death by respiratory failure might occur (18,102957).

(Read more about TOMATO)