First Immune Defense by Mountain Meadow Herbs

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if oral European barberry fruit is beneficial for acne. Details: Preliminary clinical research in adolescents 12-17 years of age with moderate or severe acne shows that taking European barberry aqueous extract 200 mg three times daily for 4 weeks reduces acne severity and decreases the number of acne lesions when compared with placebo (94824).
• Bacterial vaginosis. It is unclear if topical European barberry is beneficial for bacterial vaginosis. Details: A small clinical study in adults with bacterial vaginosis shows that applying 5 grams of a cream containing European barberry 5% with metronidazole 0.75% vaginally nightly for 7 days modestly reduces infection recurrence rate over the following three weeks when compared with metronidazole cream alone (94826).
• Breast cancer. Although there is interest in using oral European barberry for breast cancer prevention, there is insufficient reliable information about the clinical effects of European barberry for this condition.
• Dental plaque. It is unclear if brushing the teeth with a gel containing European barberry is beneficial for dental plaque. Details: Preliminary clinical research in males 11-12 years of age shows that brushing with a European barberry extract gel containing berberine 1%, three times daily for 3 weeks reduces plaque index when compared with placebo. This effect was similar to that seen with a commercial antiplaque toothpaste (Colgate) (33695).
• Diabetes. It is unclear if oral European barberry is beneficial for diabetes. Details: A small clinical study in adults with type 2 diabetes shows that taking European barberry juice 200 mL daily for 8 weeks, in conjunction with standard treatment, reduces fasting blood glucose levels by 7.5%, compared with an increase of 20% in those receiving standard treatment alone. Patients taking European barberry also had improvements in body weight, systolic and diastolic blood pressure, and total cholesterol when compared with standard treatment alone (98575).
• Gingivitis. It is unclear if brushing the teeth with a gel containing European barberry is beneficial for gingivitis. Details: Preliminary clinical research in males 11-12 years of age shows that brushing with a European barberry extract gel containing berberine 1%, three times daily for 3 weeks, reduces gingival inflammation when compared with placebo. This effect was similar to that seen with a commercial antiplaque toothpaste (Colgate) (33695).
• Hyperlipidemia. It is unclear if oral European barberry is beneficial for hyperlipidemia. Details: Meta-analyses of five small clinical trials shows that taking European barberry decreases total cholesterol by 24 mg/dL, low-density lipoprotein (LDL) cholesterol by 14 mg/dL, and triglycerides by 29 mg/dL, without significantly affecting high-density lipoprotein (HDL) cholesterol, when compared with a control intervention (102055,105756). However, because the studies included in these analyses enrolled patients with diabetes, metabolic syndrome, or nonalcoholic fatty liver disease (NAFLD), the effects of European barberry on lipid levels in patients with hyperlipidemia are unclear.
• Opioid withdrawal. It is unclear if oral European barberry is beneficial for opioid withdrawal. Details: Clinical research in patients using methadone during opioid withdrawal shows that taking European barberry root extract 500 mg twice daily for 4 weeks reduces overall symptoms of withdrawal by a large amount, but does not improve depression, anxiety, stress, or sleep quality, when compared with placebo (108156). More evidence is needed to rate European barberry for these uses.

(Read more about EUROPEAN BARBERRY)

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 stinging nettle seems to improve glycemic control in patients with diabetes. Details: A meta-analysis of 8 small heterogeneous clinical trials in adults with type 2 diabetes shows that taking stinging nettle 1.5-10 grams in divided doses daily for 8-12 weeks reduces fasting blood glucose (FBG) by 18 mg/dL when compared with placebo (102865). Glycated hemoglobin (HbA1c) was not improved, but the study durations were not adequate to detect an improvement in this measure. Despite positive results on FBG, taking stinging nettle does not seem to improve insulin secretion or measures of insulin sensitivity (91519,102865,108903). Another meta-analysis of 3 small clinical studies in adults with type 2 diabetes shows that taking stinging nettle reduces HbA1c by about 1.3% when compared with placebo. This analysis also suggests stinging nettle reduces post-prandial blood glucose by about 114 mg/dL; however, this is based on a single study. Stinging nettle did not improve fasting blood glucose or insulin resistance in this analysis (111503). The validity of these findings is limited by the low quality and heterogeneity of included studies, as well as unclear dosing. Furthermore, since most research has been conducted in Iran, it is unknown if these findings are generalizable to other geographic locations. Stinging nettle has also been used in combination with other natural medicines. One small clinical study in adults with type 2 diabetes shows that taking a product containing stinging nettle leaf extract 200 mg, milk thistle 200 mg, and Boswellia serrata gum 200 mg three times daily for 3 months reduces FBP by about 28 mg/dL and HbA1c by about 1.5%, compared with a smaller reduction in the placebo group (96742). It is unclear if this effect is due to stinging nettle, the other ingredients, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral stinging nettle is beneficial for hay fever. Details: Taking stinging nettle leaf extract 300 mg 3-7 times daily at the first sign of hay fever symptoms seems to provide subjective improvement (7035). However, adding stinging nettle to conventional allergy medication might not provide any additional benefit. One small clinical study shows that adding stinging nettle tablets (Urtidin, Barij Essence Pharmaceutical Co.) 150 mg four times daily for 1 month to treatment with loratadine and nasal saline rinses does not improve symptoms of allergic rhinitis when compared with placebo with loratadine and nasal saline rinses (96743).
• Anemia. Although there is interest in using oral stinging nettle for anemia, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Asthma. Although there is interest in using oral stinging nettle for asthma, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Benign prostatic hyperplasia (BPH). It is unclear if oral stinging nettle is beneficial for BPH. Details: A meta-analysis of clinical research, including 5 clinical studies and 1,128 patients with BPH, shows that taking stinging nettle root extract 360-600 mg in divided doses daily for 2-12 months improves peak urinary flow rate and symptom scores while modestly reducing prostate volume when compared with control. However, the validity of these results is limited by significant heterogeneity due to the variability in the products used and the specific endpoints investigated (96744). In the largest clinical trial in the analysis, patients took stinging nettle root extract 120 mg three times daily for 6 months (76406). Stinging nettle has also been evaluated in combination products. Clinical research in patients with BPH shows that taking a specific combination product (PRO 160/120, Dr. Willmar Schwabe Pharmaceuticals) containing a specific extract of stinging nettle root (WS 1031) 120 mg plus a specific extract of saw palmetto fruit (WS 1473) 160 mg twice daily for 24-48 weeks seems to improve urinary tract symptoms when compared with control; the effect may last at least 48 weeks after treatment (15195,15551,76409). However, taking a different combination product does not seem to be beneficial. A small clinical study in patients with BPH shows that taking a product containing stinging nettle root extract 240 mg, saw palmetto, pumpkin seed oil, lemon bioflavonoid, and beta-carotene, three times daily for 6 months, does not improve symptoms of BPH (5093).
• Bleeding. Topical stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some preliminary clinical research shows that applying 4 mL of a specific product (Ankaferd blood stopper, Mefar Ilaç Sanayi A.S) containing alpinia, licorice, thyme, stinging nettle, and common grape vine to the affected area reduces bleeding, but does not improve the time for episiotomy repair, when compared with using saline (31010).
• Gingivitis. Stinging nettle in a mouthwash solution has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with moderate gingival inflammation suggests that using 10 mL of mouthwash solution containing a 1:1:1 mixture of stinging nettle, juniper, and yarrow twice daily for 3 months does not reduce plaque or bleeding when compared with control (76443). It is not clear if this effect is due to stinging nettle, the other ingredients, or the combination.
• Gout. Although there is interest in using oral stinging nettle for gout, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Gulf war syndrome. It is unclear if oral stinging nettle is beneficial for Gulf war syndrome. Details: A very small exploratory clinical trial in males with Gulf war syndrome shows that taking stinging nettle leaf (Nature's Way) 1305 mg in two divided doses daily for 30 days modestly improves symptom severity when compared with placebo (108311). The clinical relevance of this finding is limited by the use of an unvalidated scoring scale. Additionally, it appears that most patients had mild, unspecified symptoms at baseline; it is unclear if stinging nettle is beneficial for moderate to severe symptoms.
• Hyperandrogenism. It is unclear if oral stinging nettle is beneficial in patients with hyperandrogenism. Details: Preliminary clinical research in females with hyperandrogenism shows that taking dried extract of stinging nettle root 300-600 mg daily for approximately 4 months decreases total and free testosterone levels, but not menstrual cycle conditions, oily skin, or acne, when compared with taking spironolactone and cyproterone (91520).
• Insect bite. Oral stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a homeopathic after-bite gel, containing stinging nettle, Echinacea, and marsh Labrador tea, on affected areas does not reduce erythema or itching after a mosquito bite when compared with placebo (89235).
• Kidney stones (nephrolithiasis). Although there is interest in using oral stinging nettle for kidney stones, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Myalgia. Although there is interest in using topical stinging nettle for myalgia, there is insufficient reliable information about the clinical effects of stinging nettle for this purpose.
• Osteoarthritis. Small clinical studies suggest that topical stinging nettle may modestly improve pain in patients with osteoarthritis. It is unclear if oral stinging nettle is beneficial. Details: Topically, stinging nettle leaf may have a counterirritant effect which may improve osteoarthritis pain in some patients. A small clinical study in patients ages 45-82 with osteoarthritis of the thumb shows that applying raw stinging nettle leaf to the thumb for 30 seconds daily for 1 week reduces pain and disability when compared with white dead nettle leaf control (12490). However, in another small clinical study in patients with knee osteoarthritis, topical application of raw stinging nettle leaf to the knee for 1 minute daily for 7 days does not seem to be more effective for reducing pain than applying a leaf from a related stingless nettle (76412). Non-raw stinging nettle has also been tried. In a small open-label study, a formulation of stinging nettle extract (Liquid PhytoCaps Nettle Leaf, Gaia Herbs) 13.33% compounded with lipobase oil-in-water emulsion and applied to the affected area twice daily for 2 weeks, modestly improves pain and function in patients with radiologically confirmed osteoarthritis when compared with baseline (76414). The validity of this finding is limited by the lack of a comparator group. Stinging nettle has also been evaluated orally, in combination with other ingredients. A clinical study in adults with knee osteoarthritis shows that taking a specific combination solution (Rosaxan, medAgil Gesundheitsgesellschaft mbH) containing stinging nettle extract 160 mg, rose hip puree 20 grams, devil's claw 108 mg, and vitamin D 200 IU daily for 12 weeks improves symptoms by an additional 28% and pain scores by an additional 33% when compared with placebo (96741). It is unclear if this effect is due to stinging nettle, the other ingredients, or the combination.
• Tinnitus. Oral stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with tinnitus shows that taking a specific product containing stinging nettle, tansy, and rose hip (Neurotec, Rose Pharmed), 100 mg orally daily for 3 months does not improve auditory thresholds when compared with placebo. However, the product improved some subjective symptoms scores, such as perceived loudness and severity scores (110512).
• Urinary tract infections (UTIs). Although there is interest in using oral stinging nettle for UTIs, there is insufficient reliable information about the clinical effects of stinging nettle for this condition. More evidence is needed to rate stinging nettle for these uses.

(Read more about STINGING NETTLE)

LIKELY SAFE ...when the fruit is consumed orally in food amounts (13527). There is insufficient reliable information available about the safety of European barberry when used orally in medicinal amounts or when used topically.

CHILDREN: LIKELY UNSAFE
when used orally in newborns. The berberine constituent of European barberry can cause kernicterus in newborns, particularly preterm neonates with hyperbilirubinemia (2589). There is insufficient reliable information available about the safety of European barberry when used orally in older children.

PREGNANCY: LIKELY UNSAFE
when used orally. Berberine 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 EUROPEAN BARBERRY)

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. Stinging nettle root 360-600 mg has been used safely for up to 1 year (5093,11230,15195,76406,96744). ...when used topically and appropriately (12490).

PREGNANCY: LIKELY UNSAFE
when used orally due to possible abortifacient and uterine-stimulant effects (4,6,19).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about STINGING NETTLE)

ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking European barberry with anticholinergic drugs might cause additive effects.  Details In vitro evidence suggests that European barberry might have anticholinergic properties (13527).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, European barberry may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro and animal evidence suggest that berberine, a constituent of European barberry, might inhibit platelet aggregation (33591,33660,33661,33694). Theoretically, European barberry might have a similar effect.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking European barberry with antidiabetes drugs might increase the risk of hypoglycemia.  Details Preliminary clinical evidence suggests that European barberry juice reduces fasting glucose levels in patients with type 2 diabetes who are also taking antidiabetes drugs (98575). Additionally, some animal studies show that berberine, a constituent of European barberry, has antiglycemic potential (33622,33667). Monitor blood glucose levels closely.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking European barberry with antihypertensive drugs might increase the risk of hypotension.  Details Animal and human research suggests that European barberry extracts can have hypotensive effects (13528,33604,98575).

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking European barberry with cholinergic drugs might decrease the effects of cholinergic drugs.  Details In vitro evidence suggests that European barberry might have anticholinergic properties (13527).

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use with drugs that have sedative properties may cause additive effects.  Details Animal research suggests that berberine, a constituent of European barberry, might have sedative effects (33650,33692). Theoretically, European barberry might have a similar effect.

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use with cyclosporine may cause additive effects.  Details Berberine, a constituent of European barberry, can reduce the metabolism and increase serum levels of cyclosporine. This effect is attributed to the ability of berberine to inhibit cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine (13524). Theoretically, European barberry might have a similar effect.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, European barberry might increase the levels and clinical effects of CYP3A4 substrates.  Details There is very preliminary evidence suggesting that berberine, a constituent of European barberry, might inhibit the CYP3A4 enzyme (13524). Theoretically, European barberry might have a similar effect.

(Read more about EUROPEAN BARBERRY)

(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).

(Read more about OREGON GRAPE)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, stinging nettle might have additive effects with antidiabetes drugs.  Details Clinical research shows that stinging nettle might decrease blood glucose levels in patients with diabetes (91519,102865).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining stinging nettle with diuretic drugs may have additive effects.  Details Animal research suggests that the above ground parts and roots of stinging nettle may have a diuretic effect (1,4,11,76402).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, stinging nettle might reduce excretion and increase levels of lithium.  Details Animal research suggests that stinging nettle has diuretic and natriuretic properties, which could alter the excretion of lithium (76402). The dose of lithium might need to be decreased.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D There is some concern that stinging nettle might decrease the effects of anticoagulant drugs such as warfarin.  Details Stinging nettle contains a significant amount of vitamin K (19). When taken in large quantities, this might interfere with the activity of warfarin.

(Read more about STINGING NETTLE)

General ...European barberry is generally well tolerated when consumed in amounts commonly found in food. A thorough evaluation of safety outcomes has not been conducted for the use of larger, medicinal amounts. Topically, European barberry seems to be well tolerated.

Hepatic ...Orally, a case of hepatitis-associated aplastic anemia is reported in an adult male after consuming European barberry 15 drops and nannari root 15 drops twice a day for 2 weeks. The patient presented with lethargy, loss of appetite, and jaundice that progressed to high-grade fevers, chills, rigors, severe pancytopenia, and abnormal liver function tests. Liver biopsy was suggestive of drug-induced liver injury. The patient was hospitalized for multiple infections and symptomatic thrombocytopenia. Despite receiving supportive care, blood transfusions, and corticosteroids, the patient died 7 weeks after diagnosis (110021). The exact reason for this adverse effect is not clear.

(Read more about EUROPEAN BARBERRY)

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).

(Read more about OLIVE)

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, stinging nettle seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea.
Topically: Contact with the raw plant causes itching, rash, and stinging.

Dermatologic ...Topically, fresh stinging nettle leaves and stalk can cause localized rash, itching, and stinging (12490,76399,76412,76414,76417,76428,76448,96746). Usually, short exposure to stinging nettle results in a transient urticarial reaction and a stinging sensation which may persist for more than 12 hours (76399,76414,76417,96746). In one report, a patient placed a fresh stinging nettle leaf on the tongue to suck out the sap of the leaf. Severe tongue edema, pain, and urticaria developed within 5 minutes. Symptoms continued for several hours after the leaf was removed (15197). In another case report, a young couple intoxicated with methamphetamine fell and laid in a stinging nettle bush for 20 minutes, after which urticaria and pain continued for 2-3 weeks, and a heightened sensitivity to cold persisted for several months (96746).

Endocrine ...A case of gynecomastia has been reported for a 33-year-old male who consumed stinging nettle tea 2 cups daily for one month prior to symptom onset. The condition subsided one month after discontinuing stinging nettle tea (76410).
There have been two cases of galactorrhea associated with the consumption of stinging nettle for one month (76410,108902). In one case, a 33-year-old female consuming stinging nettle tea showed high levels of estradiol and low levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). The levels of these hormones normalized 6 weeks after discontinuing stinging nettle tea (76410). In the other case report describing a 30-year-old female self-treating with stinging nettle 500 mg daily, hormone levels were not reported; however, a mammogram showed scattered areas of fibroglandular density and benign-appearing calcifications. This patient had complete resolution of symptoms 1 week after discontinuation of stinging nettle (108902).

Gastrointestinal ...Orally, stinging nettle root can cause gastrointestinal complaints, including diarrhea and constipation (1,7,11230). Stinging nettle above ground parts may cause mild gastrointestinal discomfort when taken on an empty stomach (7035). Stinging nettle juice may cause diarrhea (1). One patient taking a combination product containing stinging nettle root extract and pygeum bark extract (Prostatonin, Pharmaton) experienced continual gastrointestinal pain and hyperperistalsis. It is not clear if this effect was due to stinging nettle or pygeum (70230).

Genitourinary ...There is a case report of decreased ejaculatory volume associated with an herbal blend product containing stinging nettle root extract, saw palmetto extract, pumpkin seed oil extract, lemon bioflavonoid extract, and beta-carotene (5093). It is unclear if this was due to stinging nettle, other ingredients, or the combination.

Hepatic ...A case of idiosyncratic drug-induced liver disease (DILI) is reported in a 36-year-old female who presented with abdominal pain after 1 month of taking an herbal liver detox tea containing stinging nettle and other ingredients. Remarkable laboratory values included elevated liver enzymes, alkaline phosphatase, and total bilirubin. The patient received a loading dose of N-acetylcysteine and was hospitalized for 12 days (112178). However, it is unclear if the adverse effect was due to the stinging nettle, other ingredients, or the combination.

Other ...Orally, stinging nettle root can cause sweating (1,7).

(Read more about STINGING NETTLE)