Soothing Throat & Tonsil by Mountain Meadow Herbs

POSSIBLY EFFECTIVE

• Back pain. Taking devil's claw orally seems to lessen nonspecific low-back pain. Details: Some clinical research shows that taking aqueous extracts of devil's claw orally can decrease low back pain similarly to rofecoxib (Vioxx) and other non-steroidal anti-inflammatory drugs (NSAIDs). Specific products used in clinical research include Doloteffin (Ardeypharm) 800 mg three times daily for up to 1 year, WS 1531 (Dr. Willmar Schwabe GmbH & Co.) 200-400 mg three times daily for 4 weeks, and LI 174 (Rivoltan, Krewel Meuselbach GmbH) 480 mg twice daily for 4-8 weeks (8608,12477,14118,47112,47116,47117,47155,47169,47170).
• Osteoarthritis. Taking devil's claw orally, alone or in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs), seems to help decrease osteoarthritis pain. Details: Some clinical research shows that devil's claw is comparable to diacerhein (not available in the US) for improving osteoarthritis pain in the hip and knee after 16 weeks of treatment, and it decreases use of NSAIDs for pain relief. These studies used a specific powdered devil's claw root product (Harpadol, Arkopharma) 2610 mg daily for 4 months (6472,47114). Another specific devil's claw extract (Doloteffin, Ardeypharm) 2400 mg daily in 3 divided doses for 8-12 weeks, providing 60 mg harpagoside daily, has also been used (8608,14332). Some research has also evaluated devil's claw in combination with other ingredients. One clinical study shows that taking a specific combination solution (Rosaxan, medAgil Gesundheitsgesellschaft mbH) containing devil's claw 108 mg, stinging nettle 160 mg, rose hip puree 20 grams, rose hip juice concentrate 4 grams, and vitamin D 200 IU orally daily for 12 weeks improves overall symptoms by an additional 28% and pain scores by an additional 33% when compared with placebo in adults with knee osteoarthritis (96741). Another clinical study shows that a combination of devil's claw 300 mg, turmeric 200 mg, and bromelain 150 mg per capsule (AINAT, Laboratoire de Rhumatologie Appliquee), taken as two capsules three times daily for 2 weeks, or twice daily for 2 months, significantly improves acute and chronic pain in patients with osteoarthritis (91106). Also, a small, open-label clinical study in patients with mild knee osteoarthritis shows that taking a specific combination product (Tregocel, Max Biocare) providing devil's claw 1000 mg, celery seed 1000 mg, Boswellia serrata resin extract 1000 mg, ginger rhizome 330 mg, and curcumin 180 mg daily for 36 weeks reduces pain, improves functional capacity, and increases walking distance when compared with baseline (106078). The validity of the findings from these last two studies is limited by the lack of a comparator group. Additionally, it is unclear if the findings from any of these studies are due to devil's claw, other ingredients, or the combinations.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atherosclerosis. Although there is interest in using oral devil's claw for atherosclerosis, there is insufficient reliable information about the clinical effects of devil's claw for this purpose.
• Dysmenorrhea. Although there is interest in using oral devil's claw for dysmenorrhea, there is insufficient reliable information about the clinical effects of devil's claw for this purpose.
• Dyspepsia. Although there is interest in using oral devil's claw for dyspepsia, there is insufficient reliable information about the clinical effects of devil's claw for this purpose.
• Fibromyalgia. Although there is interest in using oral devil's claw for fibromyalgia, there is insufficient reliable information about the clinical effects of devil's claw for this condition.
• Gout. Oral devil's claw root extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small, open-label clinical study in patients with gout shows that taking a specific combination product (GoutFighter, Max Biocare) containing devil's claw root extract 300 mg, celery seed extract 600 mg, sour cherry extract 200 mg, and other ingredients twice daily for 45 days reduces pain, joint inflammation, and uric acid levels when compared with baseline (106488). The validity of these findings is limited by the lack of a comparator group. Additionally, it is unclear if these findings are due to devil's claw, other ingredients, or the combination.
• Migraine headache. Although there is interest in using oral devil's claw for migraine headache, there is insufficient reliable information about the clinical effects of devil's claw for this purpose.
• Myalgia. Although there is interest in using oral devil's claw for myalgia, there is insufficient reliable information about the clinical effects of devil's claw for this purpose.
• Parturition. Although there is interest in using oral devil's claw for parturition, there is insufficient reliable information about the clinical effects of devil's claw for this purpose.
• Rheumatoid arthritis (RA). It is unclear if oral devil's claw is beneficial in patients with RA. Details: Preliminary clinical research shows that taking devil's claw root extract orally (Salus-Hause-Floradix) 410 mg three times daily for 6 weeks does not improve any measures of RA symptoms when compared with baseline (8613). The validity of these results is limited by the lack of a comparator group.
• Tendinopathy. Although there is interest in using oral devil's claw for tendinopathy, there is insufficient reliable information about the clinical effects of devil's claw for this purpose.
• Wound healing. Although there is interest in using topical devil's claw for wound healing, there is insufficient reliable information about the clinical effects of devil's claw for this purpose. More evidence is needed to rate devil's claw for these uses.

(Read more about DEVIL'S CLAW)

POSSIBLY EFFECTIVE

• Burns. Topical gotu kola seems to improve the rate of burn healing. Details: Clinical research shows that applying a cream containing gotu kola 3% once daily to second degree burns increases the rate of re-epithelialization and complete healing by about 7 days when compared with silver sulfadiazine (SSD) 1% cream. Gotu kola cream also seems to reduce dryness, itching, irritation, and scar severity when compared with SSD (97027). Other research in adults with second degree burns shows that applying a gauze dressing containing gotu kola 5% and aloe 2.5%, covered with absorbent cotton wool and changed every 3 days, reduces time to healing by 1.5 days and length of hospital stay by 1.7 days when compared with the use of a gauze dressing containing chlorhexidine acetate 0.5% (97028).
• Venous insufficiency. Oral gotu kola seems to improve symptoms of venous insufficiency. Details: Clinical research shows that taking gotu kola or a specific extract of gotu kola (Centellase) 60-180 mg daily orally for 4-8 weeks seems to improve measures of circulation and decrease symptoms such as edema in patients with venous insufficiency (6887,9786,11063,11064,11066,11070,52894,52909).

POSSIBLY INEFFECTIVE

• Cognitive function. Oral gotu kola does not seem to be beneficial for cognitive function. Details: A meta-analysis of a small number of generally moderate quality clinical trials shows that taking a single dose of gotu kola, alone or in combination with other ingredients, does not improve cognitive function when compared with placebo (105334). In one study, gotu kola was taken in combination with ginkgo and docosahexaenoic acid (DHA) for 4 months by healthy, cognitively intact older adults (52880).
• Radiation dermatitis. Topical gotu kola does not seem to reduce symptoms of radiation dermatitis. Details: Clinical research in females undergoing radiotherapy for breast cancer shows that applying a cream containing gotu kola extract 7% once daily during and up to 4 weeks following radiotherapy does not reduce the severity of dermatitis when compared with no treatment or applying a moisturizing cream (102792).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Oral gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy, middle-aged females shows that applying a topical emulsion containing extracts of gotu kola 3% and Indian gooseberry 3% twice daily for 60 days improves skin hydration, some measures of skin wrinkles, and elasticity of the cheek (but not the eye) when compared with placebo (111571). It is unclear if these effects are due to gotu kola, Indian gooseberry, or the combination.
• Alzheimer disease. Although there is interest in using oral gotu kola for Alzheimer disease, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Anal fissures. It is unclear if topical gotu kola is beneficial for anal fissures. Details: In patients with chronic anal fissures who are using standard dietary and hygiene treatments, preliminary clinical research shows that taking gotu kola extract 60 mg twice daily for 8 weeks and locally applying an ointment containing gotu kola does not reduce the mean time to bleeding cessation when compared with standard treatments alone. However, pain may be modestly improved. Also, gotu kola was less effective than an unspecified flavonoid mixture used both orally and topically (105332).
• Atherosclerosis. It is unclear if oral gotu kola is beneficial for slowing the progression of atherosclerotic plaques. Details: Some preliminary clinical research shows that taking gotu kola extract 60 mg orally three times daily for 12 months helps stabilize low-density atherosclerotic plaques when compared with placebo (11062,11069). Gotu kola has also been evaluated in combination with a specific maritime pine bark product (Pycnogenol, Horphag Research). A non-randomized clinical trial shows that taking gotu kola 225 mg and Pycnogenol 150 mg in two divided doses daily for 3 months reduces plaque height and length and increases plaque echogenicity and stability when compared to control (97030). Another non-randomized clinical study in adults with atherosclerotic plaques and no other cardiovascular risk factors shows that taking gotu kola extract 100 mg and Pycnogenol 100 mg daily for up to 4 years reduces plaque progression and increases plaque echogenicity when compared with Pycnogenol alone or no treatment at all. Taking gotu kola and Pycnogenol is also associated with a reduced rate of clinical vascular events, including angina, myocardial infarction, minor transient ischemic attacks (TIAs), and minor strokes when compared with taking Pycnogenol alone or receiving no treatment at all (97029). It is unclear how these outcomes would compare to the use of gotu kola alone.
• Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral gotu kola for ADHD, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Atopic dermatitis (eczema). Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying an ointment containing 5% each of the extracts of heart's ease, gotu kola, and Oregon grape twice daily for 4 weeks does not improve eczema when compared with a base cream. However, patients with eczema on skin exposed to cold weather might experience some improvement (67372).
• Depression. Although there is interest in using oral gotu kola for depression, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Diabetic foot ulcers. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with deep diabetic foot ulcers, preliminary clinical research shows that applying a cream (WH-1 cream) containing 1.25% of gotu kola and Plectranthus amboinicus extracts in a 4:1 ratio twice daily for 2 weeks after surgical debridement is as effective as the use of a standard hydrocolloid fiber wound dressing for improving wound size. However, when compared with baseline, changes in wound size were not statistically significant (105335).
• Diabetic microangiopathy. It is unclear if oral gotu kola is beneficial for diabetic microangiopathy. Details: Preliminary clinical research shows that taking gotu kola extract 60 mg orally twice daily for 6-12 months helps increase measures of circulation and decrease edema in patients with diabetic microangiopathy (11065,11068,52917).
• Dry skin. It is unclear if topical gotu kola is beneficial for dry skin. Details: In patients with dry skin associated with type 2 diabetes, clinical research shows that topical application with 0.25 grams of a gotu kola 1% ointment twice daily, either alone or with oral gotu kola 1100 mg twice daily, for 28 days does not improve dry skin when compared with placebo. However, in a sub-group of patients with well-controlled diabetes, the combination of oral and topical gotu kola modestly improved dry skin (105329). Additionally, a small clinical study in individuals with dry skin due to working with synthetic and natural dyes shows that application of a gotu kola 2% ceramide-based cream to the hands and arms twice daily for 4 weeks improves skin barrier hydration, as measured by hydration of the stratum corneum and skin acidity, when compared to baseline. These improvements were similar to those seen with a ceramide 5% cream (109554). As the gotu kola cream was formulated with ceramide, it is unclear if these findings are due to gotu kola, ceramide, or the combination.
• Epilepsy. Although there is interest in using oral gotu kola for epilepsy, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Generalized anxiety disorder (GAD). It is unclear if oral gotu kola is beneficial for GAD. Details: In patients with GAD, preliminary clinical research shows that taking gotu kola extract 500 mg twice daily for 60 days reduces symptoms of anxiety, depression, and stress by 22% to 26% when compared with baseline (105333). The validity of these findings is limited by the lack of a comparator group.
• Hemorrhoids. It is unclear if topical gotu kola is beneficial for hemorrhoids. Details: Preliminary clinical research in patients with chronic hemorrhoids, as well as patients with acute symptoms following a hemorrhoidectomy or surgical treatment for hemorrhoidal thrombosis, shows that taking gotu kola extract (Centella complex) 60 mg twice daily for 15 weeks and locally applying an ointment (Proctocella) containing gotu kola, arnica, and aloe, in conjunction with standard treatments, does not reduce the mean time to bleeding cessation when compared with standard treatments alone. Anal irritation was modestly improved in the patients with chronic hemorrhoids and in those undergoing treatment for hemorrhoidal thrombosis, but not in those that had undergone a hemorrhoidectomy (105336).
• Herpes zoster (shingles). Although there is interest in using oral gotu kola for shingles, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Hypertension. It is unclear if oral gotu kola is beneficial for hypertension. Details: Preliminary clinical research in patients with hypertension shows that drinking a tea made by boiling gotu kola 4 grams in 250 mL water three times daily for 3 days modestly reduces systolic and diastolic blood pressure when compared with baseline. After consuming the tea, about 40% of patients had normal or high-normal systolic blood pressure and 77% had optimal or normal diastolic blood pressure, compared with 0% and 45%, respectively, prior to consumption (105330). The validity of these findings is limited by the lack of a comparator group.
• Hypertrophic scars. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that topical use of a specific silicone gel (Bangkok Botanica) containing 15% extracts of gotu kola, onion, aloe, and paper mulberry, starting 2 weeks after surgery and continuing for 6 months, moderately improves the height and pliability of the post-surgical hypertrophic scar when compared with a silicone placebo gel. There was no effect on pigmentation or vascularity (102793). It is unknown whether any benefit is related to gotu kola, other ingredients, or their combination.
• Idiopathic interstitial pneumonia. Oral gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small observational registry study in males less than 65 years old with idiopathic interstitial pneumonia has found that taking a specific gotu kola extract (Centellicum; Horphag Research) 225 mg three times daily in combination with a standardized extract of maritime pine bark (Pycnogenol, Horphag Research) 50 mg three times daily for 8 months is associated with a modest improvement in Karnofsky Performance Scale scores and a reduction in fatigue when compared with pirfenidone (108862). However, the validity of these findings is limited by the unblinded, non-randomized nature of the study.
• Keloids. It is unclear if oral or topical gotu kola are beneficial for keloids. Details: There is some early evidence that applying a specific extract of gotu kola (Madecassol) topically might help reduce keloids and hypertrophic scarring (13558). Gotu kola has also been taken orally for keloids. Preliminary clinical research in patients at high risk for keloids shows that taking a specific extract of gotu kola (Centellicum, Horphag Research Ltd) 450 mg daily for 4 weeks starting on the second week after surgery seems to improve scar homogeneity and regularity (99756). However, the reliability of these results is limited because patients in this study were not randomized or blinded to different interventions.
• Laser skin resurfacing. It is unclear if topical gotu kola is beneficial for recovery from laser skin resurfacing. Details: A small clinical trial shows that applying a gel containing gotu kola extract (ECa 233) 0.05% four times daily for 7 days, then twice daily for 3 months, improves wound healing following laser resurfacing for facial acne. Redness returned to baseline levels by day 7, in contrast to day 28 on the side treated with a placebo gel. The general wound appearance and crusting were also improved on the side on which the gotu kola extract gel was applied (102794).
• Osteoarthritis. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large, single-blind clinical study in adults with knee osteoarthritis causing moderate pain shows that applying a specific cream (TMP-4) containing extracts of gotu kola leaf, sesame seed, soybean, and mangosteen peel four times daily for 4 weeks provides similar improvement in pain scores when compared with diclofenac 1% gel. Topical TMP-4 cream also seems to improve knee stiffness, stair climbing, and mobility similarly to diclofenac gel. However, patient impression of overall improvement was higher with diclofenac (110128). The validity of this study is limited by inadequate blinding.
• Scarring. It is unclear if topical gotu kola is beneficial for scarring or tenderness from scarring. Details: Preliminary clinical research in patients without a history of keloid formation suggests that applying a specific cream (Alpha Centella, not available in the US) containing gotu kola and Bulbine frutescens extracts twice daily for 6-8 weeks following suture removal might help to reduce scarring (11072). Also, a large clinical study in adults who underwent carpal tunnel release surgery shows that applying gotu kola cream 1% three times daily for 6 months after suture removal marginally improves self-reported scar tenderness pain when compared with control, and modestly improves scarring scores when compared to baseline (112425). However, the interpretation of these findings is limited by patient-reported outcomes and insufficient validity of the scar scoring tool in this population.
• Skin grafts. Although there is interest in using topical gotu kola for skin graft recovery, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Stretch marks (striae gravidarum). It is unclear if oral gotu kola is beneficial for stretch marks; topical gotu kola has only been evaluated in combination with other ingredients. Details: Preliminary clinical research in females with stretch marks shows that taking a specific extract of gotu kola (Centellicum, Horphag Research Ltd) 225 mg three times daily for 6 weeks increases skin thickness, elasticity, and perfusion when compared with a stretch mark minimizer cream (Clarins) and regular control cream (99757). The validity of these results is limited by the fact that patients were not randomized or blinded to the different interventions. Gotu kola has also been evaluated topically in combination with other ingredients. Preliminary clinical research shows that applying a specific mixture of gotu kola, vitamin E, and collagen-elastin hydrolysates in a cream (Trofolastin, not available in the US) daily during the second and third trimesters reduces stretch marks when compared with a placebo cream (13559). Another small clinical study shows that applying a specific mixture of gotu kola, vitamin E, essential fatty acids, hyaluronic acid, elastin, and menthol in an ointment (Verum, not available in the US) helps decrease the formation of stretch marks during pregnancy when compared with placebo (11073). Other preliminary clinical research in patients without previous striae shows that applying a specific formula containing hydroxyprolisilane C, rosehip oil, gotu kola triterpenes, and vitamin E (Velastisa Antiestrías, ISDIN) twice daily, beginning at week 10-14 and continuing throughout pregnancy, decreases the severity of both new and old stretch marks and the incidence of stretch marks when compared with placebo (92507). It is unclear if the effects seen in these studies are due to gotu kola, other ingredients, or the combinations.
• Systemic lupus erythematosus (SLE). Although there is interest in using oral gotu kola for SLE, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Tonsillitis. Although there is interest in using oral gotu kola for tonsillitis, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Venous thromboembolism (VTE). It is unclear if oral gotu kola is beneficial for VTE prevention. Details: Preliminary clinical research shows that gotu kola decreases edema and improves measures of circulation in patients traveling on airplanes for more than 3 hours when compared to a control group receiving no treatment (11067). However, it is unknown if these changes reduce the incidence of clots.
• Wound healing. Although there is interest in using topical gotu kola for wound healing, there is insufficient reliable information about the clinical effects of gotu kola for this purpose.
• Wrinkled skin. It is unclear if topical gotu kola is beneficial for wrinkled skin. Details: Small, low-quality studies in healthy adults suggest that topical formulations of gotu kola extract or the constituent asiaticoside 0.1% or 0.2% applied 1-3 times daily have shown modest benefit for wrinkled skin. Cream or gel formulations were used for 12 weeks for periorbital wrinkles and a lipstick was used for 8 weeks for lip wrinkles. However, the extent of benefit is not clear and meta-analyses are limited to a very small number of studies with varied comparator groups, including placebo, vehicle, tretinoin 0.02%, and Pueraria mirifica extract (106639). More evidence is needed to rate gotu kola for these uses.

(Read more about GOTU KOLA)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dyspepsia. Oral olive leaf extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in healthy adults shows that taking a specific combination product containing olive leaf extract 24% and prickly pear cactus 33% (Mucosave, Bionap S.R.L.) 400 mg daily for 8 weeks seems to improve dyspepsia and other gastrointestinal symptoms when compared with placebo (105904). It is unclear if this benefit would occur in patients with clinically diagnosed dyspepsia.
• Exercise-induced respiratory infections. It is unclear if oral olive leaf extract is beneficial for reducing respiratory infections from exercise. Details: A small clinical study in high school athletes shows that taking one tablet of olive leaf extract providing eleuropein 100 mg daily for 2 months during training season does not reduce the incidence of the common cold when compared with placebo. While it may reduce the number of sick days by 28%, a sub-group analysis suggests that this reduction is only evident in female athletes (101860).
• Gastroesophageal reflux disease (GERD). Although there is interest in using oral olive leaf for GERD, there is insufficient reliable information about the clinical effects of olive for this condition.
• Herpes zoster (shingles). Although there is interest in using oral olive leaf for shingles, there is insufficient reliable information about the clinical effects of olive for this condition.
• Influenza. Although there is interest in using oral olive leaf for influenza, there is insufficient reliable information about the clinical effects of olive for this condition.
• Metabolic syndrome. It is unclear if oral olive leaf extract is beneficial for improving body composition and cardiovascular risk factors in patients with metabolic syndrome. Details: A small clinical trial in overweight, middle-aged males at risk for metabolic syndrome shows that taking four capsules of olive leaf extract providing oleuropein 51.1 mg and hydroxytyrosol 9.7 mg daily for 12 weeks improves insulin sensitivity by 15% when compared with placebo. However, body composition, blood pressure, cholesterol levels, and other cardiovascular risk factors were not improved (92245).
• Osteoarthritis. It is unclear if oral olive fruit or leaf extract is beneficial for improving osteoarthritis. Details: Preliminary clinical research shows that taking a freeze-dried aqueous extract of olive fruit 400 mg daily for 8 weeks decreases pain and increases mobility in people with osteoarthritis (14844). Other preliminary clinical research in adults with knee osteoarthritis shows that taking olive leaf extract 50.1 mg daily for 4 weeks improves overall pain measurements by 14%, compared to only 4% in the placebo group. However, many individual measurements of pain are not improved (92252).
• Osteoporosis. It is unclear if oral olive leaf extract is beneficial for osteoporosis. Details: Clinical research shows that taking olive leaf extract (Bonolive, BioActor BV) 250 mg daily for 12 months, along with elemental calcium 400 mg daily, increases osteocalcin levels by about 32% when compared to baseline; this increase was significant when compared to those taking calcium 400 mg plus placebo, who showed a 6% decrease in osteocalcin levels. However, taking olive leaf extract does not significantly increase bone mineral density of the lumbar spine or femur neck when compared with placebo (92247).
• Rheumatoid arthritis (RA). It is unclear if oral olive fruit extract is beneficial for improving RA symptoms. Details: Preliminary clinical research in adults with RA shows that taking an aqueous freeze-dried extract of olive fruit 400 mg daily for 8 weeks does not improve symptoms when compared with control (14844). More evidence is needed to rate the effectiveness of olive for these uses.

(Read more about OLIVE)

POSSIBLY EFFECTIVE

• Psoriasis. Several clinical studies suggest that topical Oregon grape extract cream modestly improves symptoms and quality of life in patients with psoriasis. Details: Clinical research shows that applying a specific Oregon grape extract 10% cream (Relieva, Apollo Pharmaceutical) to the affected area 2-3 times daily for up to 12 weeks modestly decreases the severity of psoriasis and improves quality of life in patients with psoriasis when compared with placebo (854,857,14000,14333). One small clinical study shows that this specific cream might be as effective as calcipotriene (Dovonex) cream for some patients (14000).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). It is unclear if topical Oregon grape extract cream is beneficial in patients with atopic dermatitis. Details: A small, open-label trial in adults with atopic dermatitis shows that applying a specific Oregon grape extract 10% cream (Relieva, Apolla Pharmaceutical) to the affected area three times daily for 12 weeks improves the severity and area of eczema when compared to baseline (67370). However, the validity of this finding is limited by the lack of a comparator group. In contrast, applying a combination of Oregon grape, heart's ease, and gotu kola extracts for 4 weeks does not improve eczema when compared with a base cream, although there appears to be improvement in eczema for skin exposed to cold weather (67372).
• Dyspepsia. Although there has been interest in using oral Oregon grape for dyspepsia, there is insufficient reliable information about the clinical effects of Oregon grape for this purpose.
• Gastroesophageal reflux disease (GERD). Although there has been interest in using oral Oregon grape for GERD, there is insufficient reliable information about the clinical effects of Oregon grape for this purpose.
• Peptic ulcers. Although there has been interest in using oral Oregon grape for peptic ulcers, there is insufficient reliable information about the clinical effects of Oregon grape for this purpose. More evidence is needed to rate Oregon grape for these uses.

(Read more about OREGON GRAPE)

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)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cancer. Oral slippery elm has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Retrospective population research has found that taking a specific product containing burdock root, Indian rhubarb, sheep sorrel, and slippery elm bark (Essiac, Resperin Canada Limited) does not improve quality of life in breast cancer patients and may have a negative effect on physical well-being (37419).
• Constipation. Although there has been interest in using oral slippery elm for constipation, there is insufficient reliable information about the clinical effects of slippery elm for this purpose.
• Cough. Although there has been interest in using lozenges containing slippery elm for cough, there is insufficient reliable information about the clinical effects of slippery elm for this purpose.
• Diarrhea. Although there has been interest in using oral slippery elm for diarrhea, there is insufficient reliable information about the clinical effects of slippery elm for this purpose.
• Inflammatory bowel disease (IBD). Although there has been interest in using oral slippery elm for IBD, including Crohn disease and ulcerative colitis, there is insufficient reliable information about the clinical effects of slippery elm for this purpose.
• Irritable bowel syndrome (IBS). Oral slippery elm has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific formulation containing slippery elm inner bark, lactulose, oat bran, and licorice root can improve stool frequency by 20% and reduce abdominal pain and bloating in people with constipation-predominant IBS when compared to baseline. Also, taking a different formulation containing slippery elm inner bark, bilberry fruit, cinnamon quilts, and agrimony aerial parts can reduce abdominal pain, bloating, and flatulence in people with diarrhea-predominant IBS when compared to baseline, although stool frequency is increased in these individuals as well (35462). It is unclear if these findings are due to slippery elm, other ingredients, or the combination.
• Peptic ulcers. Although there has been interest in using oral slippery elm for peptic ulcers, there is insufficient reliable information about the clinical effects of slippery elm for this purpose.
• Pharyngitis. It is unclear if lozenges containing slippery elm are beneficial in patients with sore throat. Details: Slippery elm has demulcent properties and, when added to lozenges, may soothe sore throats (272,512,1740). However, clinical research is lacking. More evidence is needed to rate slippery elm for these uses.

(Read more about SLIPPERY ELM)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cough. Although there has been interest in using oral usnea for cough, there is insufficient reliable information about the clinical effects of usnea for this purpose.
• Human papillomavirus (HPV). Topical usnic acid, a constituent of usnea, has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in patients with HPV genital infection undergoing radiosurgical treatment of HPV lesions shows that vaginal application of a specific product containing zinc sulfate and the usnea constituent usnic acid (Zeta N, Bergamon Italia), before and after radiosurgical treatment of HPV lesions, improves wound healing and reduces the recurrence of infection for up to 6 months after surgical treatment when compared with radiosurgical treatment alone (81573). It is unclear if these effects are due to usnic acid, zinc sulfate, or the combination.
• Obesity. Although there has been interest in using oral usnea for weight loss, there is insufficient reliable information about the clinical effects of usnea for this purpose.
• Pain (acute). Although there has been interest in using oral usnea for acute pain, there is insufficient reliable information about the clinical effects of usnea for this purpose.
• Tinea pedis. Although there has been interest in using topical usnea for tinea pedis, there is insufficient reliable information about the clinical effects of usnea for this purpose.
• Wound healing. Although there has been interest in using topical usnea for wound healing, there is insufficient reliable information about the clinical effects of usnea for this purpose. More evidence is needed to rate usnea for these uses.

(Read more about USNEA)

There is insufficient reliable information available about the effectiveness of white oak bark.

(Read more about WHITE OAK)

POSSIBLY SAFE ...when used orally and appropriately. Devil's claw extract has been used with apparent safety in doses of up to 2400 mg daily for up 12 weeks (6472,8608,14332,14418,47112,47114,47116,47117,47155). There is insufficient reliable information available about the safety of devil's claw when used orally long-term or when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used orally. Anecdotal evidence suggests that devil's claw has oxytocic effects in humans. Also, in vitro research shows that moderate to high doses of devil's claw root extract induce contractions of isolated uterine muscle from pregnant and nonpregnant rats (94689); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about DEVIL'S CLAW)

POSSIBLY SAFE ...when used topically and appropriately. Gotu kola has been used safely in a cream or ointment for up to 10 weeks (11072,11073,67372,102792,105329,105335). An emulsion containing gotu kola extract 3% and other ingredients has been applied safely to the skin twice daily for up to 60 days (111571). ...when used orally and appropriately. Gotu kola extract has been used with apparent safety in doses of up to 180 mg daily for up to 12 months or 1000 mg daily for 60 days. Dried gotu kola has been used with apparent safety in doses of up to 2200 mg daily for 4 weeks (6887,11062,11063,11064,11065,11066,11067,11068,11069,11070)(11071,99756,99757,99758,105329,105332,105333). A specific gotu kola extract (Centellicum, Horphag Research Ltd) 450-675 mg daily has been used with apparent safety for up to 6 weeks (99756,99757).

PREGNANCY: POSSIBLY SAFE
when used topically and appropriately (11073,13559). There is insufficient reliable information available about the safety gotu kola when used orally during pregnancy; avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about GOTU KOLA)

LIKELY SAFE ...when olive fruit is used orally and appropriately in amounts commonly found in foods.

POSSIBLY SAFE ...when olive leaf extract is used orally and appropriately. Olive leaf extract providing 51-100 mg oleuropein daily has been used with apparent safety for 6-8 weeks (92245,92247,101860). There is insufficient reliable information available about the safety of olive fruit extract when used in amounts greater than those found in foods.

PREGNANCY AND LACTATION:
Insufficient reliable information available; stick with amounts commonly found in foods.

(Read more about OLIVE)

LIKELY SAFE ...when used orally in amounts commonly found in food.

POSSIBLY SAFE ...when used topically and appropriately (854,856,857,14000,14333). A specific 10% Oregon grape cream (Relieva, Apollo Pharmaceutical) has been used with apparent safety in studies lasting up to 12 weeks (14000,14333). There is insufficient reliable information available about the safety of Oregon grape when used orally in medicinal amounts.

CHILDREN: LIKELY UNSAFE
when used orally in newborns. The berberine constituent of Oregon grape can cause kernicterus in newborns, particularly preterm neonates with hyperbilirubinemia (2589).

PREGNANCY: LIKELY UNSAFE
when used orally. Berberine, a constituent of Oregon grape, is thought to cross the placenta and may cause harm to the fetus. Kernicterus has developed in newborn infants exposed to berberine (2589).

LACTATION: LIKELY UNSAFE
when used orally. Berberine and other harmful constituents can be transferred to the infant through breast milk (2589).

(Read more about OREGON GRAPE)

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)

POSSIBLY SAFE ...when used orally and appropriately (4,12,272,512,1740).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using. Slippery elm bark has historically been inserted into the cervix to induce abortion. As a result, slippery elm has been reported in some sources to have abortifacient activity. However, there is no reliable information available about whether slippery elm has abortifacient activity when taken orally.

(Read more about SLIPPERY ELM)

POSSIBLY SAFE ...when used topically and appropriately (12).

POSSIBLY UNSAFE ...when used orally. There are case reports of hepatotoxicity associated with compounds containing usnic acid, a constituent of usnea (7091,81595,81600,81607,81612,81619).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about USNEA)

POSSIBLY SAFE ...when used orally for up to 3-4 days for treating diarrhea (2,12,7). ...when used topically up to 2-3 weeks on intact skin (2).

LIKELY UNSAFE ...when used topically on extensive areas of damaged skin or for longer than 2-3 weeks (2).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about WHITE OAK)

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, devil's claw might increase levels of drugs metabolized by CYP2C19.  Details In vitro research shows that devil's claw might inhibit CYP2C19, although this has not been reported in humans (12479).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, devil's claw might increase levels of drugs metabolized by CYP2C9.  Details In vitro research shows that devil's claw might inhibit CYP2C9, although this has not been reported in humans (12479).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, devil's claw might increase levels of drugs metabolized by CYP3A4.  Details In vitro research shows that devil's claw might inhibit CYP3A4, although this has not been reported in humans (12479).

H2-BLOCKERS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, devil's claw might decrease the effectiveness of H2-blockers.  Details Devil's claw has been reported to increase stomach acid, which might interfere with the effects of H2-blockers (19).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, devil's claw might increase levels of P-glycoprotein substrates.  Details In vitro research shows that devil's claw inhibits P-glycoprotein, which transports many drugs out of cells (17325). This might increase intracellular levels of P-glycoprotein substrates, although it is unclear if this effect would be clinically important (17325).

PROTON PUMP INHIBITORS (PPIs) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, devil's claw might decrease the effectiveness of PPIs.  Details Devil's claw has been reported to increase stomach acid, which might interfere with the effects of PPIs (19).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Devil's claw might increase the activity of warfarin.  Details In one case report, purpura occurred in a patient taking warfarin and devil's claw concurrently. This might indicate over-anticoagulation (613). It is unclear if this was due to Devil's claw or other contributing factors.

(Read more about DEVIL'S CLAW)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking gotu kola might increase the sedative effects of CNS depressants.  Details In vitro research suggests that gotu kola may have sedative effects via binding of GABA receptors (6887,11071).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking gotu kola with hepatotoxic drugs might have additive adverse effects.  Details There are at least four case reports of hepatotoxicity associated with the use of gotu kola. However, more information is needed to determine if gotu kola was the causative factor in these cases (13182,92506).

(Read more about GOTU KOLA)

(Read more about OLIVE)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Oregon grape might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro and in vivo research suggests that berberine, a constituent of Oregon grape, can inhibit platelet aggregation (33660,33694).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = A Theoretically, Oregon grape might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Clinical research suggests that berberine, a constituent of Oregon grape, can lower blood glucose levels (20579,34247,34265,34282).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Oregon grape might increase the risk of hypotension when taken with antihypertensive drugs.  Details Animal research suggests that berberine, a constituent of Oregon grape, can have hypotensive effects (33692,34308). Also, an analysis of clinical evidence suggests that taking berberine in combination with amlodipine (Norvasc) can lower systolic and diastolic blood pressure when compared with taking amlodipine alone (91956).

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Oregon grape might increase the sedative effects of CNS depressants.  Details Animal research suggests that berberine, a constituent of Oregon grape, can have sedative effects (13519,33650,33664,33692).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Oregon grape might increase the effects and adverse effects of cyclosporine.  Details Berberine, a constituent of Oregon grape, can reduce metabolism of cyclosporine and increase serum levels. It might inhibit cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine (13524).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP2C9.  Details Preliminary clinical evidence suggests that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2C9 (CYP2C9) (34279).

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP2D6.  Details In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2D6 (CYP2D6) (21117,34279,34297).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP3A4.  Details In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, moderately inhibits cytochrome P450 3A4 (CYP3A4) (13524,21114,34279,34297).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Oregon grape might increase serum levels of drugs that are P-glycoprotein (P-gp) substrates.  Details In vitro research suggests that Oregon grape extracts inhibit P-gp efflux (112342).

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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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ORAL DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, slippery elm may slow the absorption and reduce serum levels of oral drugs.  Details Slippery elm inner bark contains mucilage, which may interfere with the absorption of orally administered drugs (19).

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(Read more about WHITE OAK)

General ...Orally, Devil's claw seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Allergic skin reactions, diarrhea, dyspepsia.
Serious Adverse Effects (Rare):
Orally: Gastrointestinal bleeding.

Cardiovascular ...In one case report, a healthy patient with normal blood pressure presented with hypertension after taking devil's claw 250 mg twice daily for 2 weeks. It gradually resolved after discontinuation of devil's claw (92017). Some animal research shows that devil's claw might have negative chronotropic, as well as positive and negative inotropic, effects (8609). However, these effects have not been documented in humans.

Dermatologic ...Rarely, allergic skin reactions have been reported in patients taking devil's claw (8608,14418).

Endocrine ...In one case report, a 65-year-old female developed psychomotor agitation, nausea, and distress from euvolemic hyponatremia secondary to inappropriate secretion of antidiuretic hormone (SIADH) within 1 month of starting daily treatment with devil's claw. Within 5 days of discontinuing the product and receiving sodium replacement, the symptoms resolved. Two months later, the patient re-initiated devil's claw and again developed euvolemic hyponatremia (96747).

Gastrointestinal ...Gastrointestinal side effects, including mild gastrointestinal upset, diarrhea, anorexia, acid reflux, or loss of taste, have been reported in some individuals receiving devil's claw, especially at high doses (6472,8608,8613,14332,14418,47112,47116,47144,47169). Gastrointestinal complaints have been reported in 9% to 18% of patients taking a specific devil's claw extract (Doloteffin, Ardeypharm) (8608,47169), while diarrhea was reported in about 8% of patients taking devil's claw (Harpadol, Arkopharma) (6472). Several cases of gastrointestinal bleeding have been reported (104977).

Genitourinary ...Dysmenorrhea was reported in one patient taking a specific devil's claw extract (Doloteffin, Ardeypharm) for 8 weeks (8608).

Neurologic/CNS ...In a trial of devil's claw, one patient withdrew after 4 days of therapy due to a throbbing frontal headache, as well as tinnitus, anorexia, and loss of taste (8613). Rarely, dizziness, somnolence, and insomnia have been reported (47116,47169). It is unclear if these symptoms were caused by devil's claw.

Psychiatric ...Rarely, anxiety has been reported in patients taking devil's claw (8608).

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General ...Orally and topically, gotu kola seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastric irritation and nausea.
Topically: Eczema.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity.

Dermatologic ...Topically, gotu kola may cause eczema (10277,10278). Also, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (4,6887,9789,52875,52887,52896,52902). One specific gotu kola product (Blasteostimulina,Almirall, S. A.) has been reported to cause allergic contact dermatitis. However, not all patients with reactions to this product are sensitive to gotu kola; some patients are sensitive to neomycin, another ingredient in the product (52875). Madecassol ointment (Rona Laboratories Limited) is another gotu kola product that has resulted in allergic contact dermatitis. Controlled testing suggests that this product can cause this adverse effect in about 8% of patients (9789). Centellase cream has also caused allergic contact dermatitis in at least two cases (52887,52888).

Gastrointestinal ...In some patients, gotu kola can extract cause gastrointestinal upset and nausea (780,6887,52894).

Hepatic ...There is concern that gotu kola may cause liver toxicity in some patients. There are at least four case reports of hepatotoxicity associated with gotu kola; however, hepatotoxic contaminants cannot be ruled out, as laboratory analysis was not conducted on the products used. Additionally, the doses of gotu kola used in these cases were not reported (13182,92506). In a clinical trial where liver function was monitored, taking gotu kola 120 mg daily for 6 months was not associated with changes in liver function (11065).
In one case of hepatotoxicity, a 61-year-old female developed elevated liver transaminase and total bilirubin levels after taking gotu kola tablets for 30 days. Liver biopsy showed granulomatous acute hepatitis. Months later, the patient took gotu kola again and developed elevated liver transaminases after 2 weeks. In another case, a 52-year-old female developed symptoms of hepatitis and increased liver transaminases after taking gotu kola for 3 weeks. Biopsy indicated chronic hepatitis and granulomas, areas of necrosis, and cirrhotic transformation. Liver function normalized after discontinuation of gotu kola. In a third case, a 49-year-old female developed symptoms of hepatitis after taking gotu kola for 2 months. Biopsy revealed granulomatous hepatitis. Liver function normalized after discontinuation of gotu kola (13182). In a fourth case, a 15-year-old female taking an unknown dose of gotu kola and lymecycline for 6 weeks for acne experienced acute liver failure with abdominal pain and vomiting, as well as elevated liver transaminases, bilirubin, international normalized ratio (INR), and prothrombin. Liver function returned to normal after both products were discontinued (92506).

Immunologic ...Topically, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (4,6887,9789,52875,52887,52896,52902). One specific gotu kola product (Blasteostimulina, Almirall, S. A.) has been reported to cause allergic contact dermatitis in some patients. However, not all patients who react to this product are sensitive to gotu kola; some are sensitive to neomycin, another ingredient in the product (52875). Madecassol ointment (Rona Laboratories Limited) is another gotu kola product that has resulted in allergic contact dermatitis. Controlled testing suggests that this product can cause this adverse effect in about 8% of patients (9789). Centellase cream has also caused allergic contact dermatitis in at least two cases (52887,52888).

Psychiatric ...A case of night eating syndrome has been reported for a 41-year-old female who had been taking a gotu kola tincture (dose not specified) for 2 years. Symptoms resolved after gotu kola use was discontinued (52878).

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General ...Orally, olive fruit is well tolerated when used in typical food amounts. Olive leaf extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Headache and stomach discomfort.

Dermatologic ...Orally, one patient in one clinical trial reported bad skin and acne after using olive leaf extract (101860).

Gastrointestinal ...Orally, three patients in one clinical trial reported stomach ache after using olive leaf extract (101860).

Neurologic/CNS ...Orally, three patients in one clinical trial reported headache after using olive leaf extract (101860).

Psychiatric ...In one case report, a 67-year-old female experienced irritability, anger, a lack of control, and feelings of sadness and negativity after consuming a multi-ingredient product containing olive leaf extract 5 grams, horseradish root, and eyebright daily for 38 days. All psychiatric symptoms disappeared within days of stopping the combined product. It is hypothesized that the hydroxytyrosol component of olive leaf extract contributed to these symptoms due to its chemical similarity to dopamine; however, it is not clear if these symptoms were due to the olive leaf extract or to the other ingredients (96245).

Pulmonary/Respiratory ...Olive tree pollen can cause seasonal respiratory allergy (1543).

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General ...Orally, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted. Topically, Oregon grape seems to be well tolerated.

Dermatologic ...Topically, Oregon grape may cause itching, burning, and skin irritation in some patients (854,14000).

Immunologic ...Topically, Oregon grape may cause allergic skin reactions in some patients (854,14000).

(Read more about OREGON GRAPE)

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, slippery elm seems to be well tolerated. A thorough evaluation of safety outcomes with topical use of slippery elm has not been conducted.

Dermatologic ...Topically, slippery elm extracts can cause contact dermatitis. The pollen is an allergen (6). Contact dermatitis and urticaria have been reported after exposure to slippery elm or an oleoresin contained in the slippery elm bark (75131).

(Read more about SLIPPERY ELM)

General ...There is currently a limited amount of information about the adverse effects of usnea. Orally, usnea might be unsafe. The constituent usnic acid has been associated with hepatotoxicity. Topically, usnea is generally well tolerated.
Most Common Adverse Effects:
Topically: Usnic acid, a constituent of usnea, can cause conjunctivitis, contact dermatitis, and local irritation.
Serious Adverse Effects (Rare):
Orally: Usnic acid, a constituent of usnea, has been associated with reports of hepatotoxicity.

Dermatologic ...Topically, a compound containing zinc sulfate and usnic acid, a constituent of usnea, has been reported to cause local irritation and contact dermatitis (81573).

Hepatic ...Orally, usnic acid, a constituent of usnea, has been associated with reports of hepatotoxicity. From July to December 2000 there were at least seven cases of acute hepatotoxicity in patients taking LipoKinetix, a product containing usnic acid as sodium usniate. Symptoms including nausea, weakness and fatigue, abdominal pain, and yellowing of the skin usually developed from 2 weeks to 3 months after starting LipoKinetix and resolved upon discontinuation (7091). It is unclear if the sodium usniate ingredient is the cause of these adverse events. There are also individual case reports suggesting the development of hepatotoxicity related to the use of other weight loss products containing usnic acid (81595,81600,81607,81612,81619).

Immunologic ...Topically, usnea and its constituent, usnic acid, can cause allergic contact dermatitis with respiratory symptoms (11720,81580,81632).

Ocular/Otic ...Topically, usnic acid, a constituent of usnea, can cause conjunctivitis (11720).

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General ...White oak bark seems to be well tolerated when used orally to topically on unbroken skin, short-term. White oak pollen may cause allergic reactions in some people (86395).

Immunologic ...White oak pollen may cause allergic reactions in some people (86395).

(Read more about WHITE OAK)