Fevera by HerbaSway Laboratories, LLC

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral Baikal skullcap for allergic rhinitis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Anxiety. Although there has been interest in using oral Baikal skullcap for anxiety, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Atherosclerosis. Although there has been interest in using oral Baikal skullcap for atherosclerosis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral Baikal skullcap for ADHD, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Bronchiolitis. Intravenous Baikal skullcap has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that a combination of Baikal skullcap, forsythia, and honeysuckle, known as Shuang Huang Lian in traditional Chinese medicine, given intravenously, with or without antibiotics, decreases the duration of cough by about 1.5-2 days, the duration of wheezing by about 2 days, and the duration of hospitalization by about 2-3 days when compared with antibiotics alone in children with respiratory syncytial virus (RSV) infection. Baikal skullcap injection was administered as a 20 mL dose for patients under 6 months, a 40 mL dose for patients 7-36 months, or a 60 mL dose for patients older than 36 months (12613).
• Cancer. Although there has been interest in using oral Baikal skullcap for cancer, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Diabetes. It is unclear if oral Baikal skullcap is beneficial in patients with diabetes. Details: A very small clinical trial in patients with uncontrolled diabetes taking metformin 500 mg daily shows that taking Baikal skullcap extract 3.52 grams in three divided doses daily for 8 weeks does not decrease levels of fasting glucose or insulin or improve levels of glycated hemoglobin (HbA1c) when compared with placebo. However, taking Baikal skullcap reduces blood glucose levels during an oral glucose tolerance test (OGTT) at 60 minutes, but not 120 minutes, when compared with placebo (101738). This study may have been inadequately powered to detect a difference between groups.
• Epilepsy. Although there has been interest in using oral Baikal skullcap for epilepsy, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hand, foot, and mouth disease. It is unclear if intravenous Baikal skullcap is beneficial in patients with hand, foot, and mouth disease. Details: Low-quality observational research in children hospitalized with severe hand, foot, and mouth disease has found that children who are given Baikal skullcap intravenously as a Tanreqing injection 0.3-0.5 mL/kg once daily have a shorter duration of fever, oral ulcers, and rash, as well as reduced viral load, when compared with those given ribavirin 10 mg/kg once daily (96281). The validity of these findings is limited by the retrospective nature of the study.
• Headache. Although there has been interest in using oral Baikal skullcap for headache, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hemorrhoids. Although there has been interest in using oral Baikal skullcap for hemorrhoids, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hepatitis. Although there has been interest in using oral Baikal skullcap for hepatitis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• HIV/AIDS. Although there has been interest in using oral Baikal skullcap for HIV/AIDS, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Insomnia. Although there has been interest in using oral Baikal skullcap for insomnia, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Osteoarthritis. Oral Baikal skullcap 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 product (Limbrel, Primus Pharmaceuticals) that contains flavocoxid, a blend of Baikal skullcap extract and catechu flavonoid extract, 500 mg once or twice daily for up to 12 weeks reduces symptoms of osteoarthritis of the knee when compared with baseline. These studies found no significant difference between this combination product and naproxen 440 mg once daily to 500 mg twice daily for reducing symptoms (17030,18012,92776). However, in 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). See the Adverse Effects section for more information.
• Peyronie disease. It is unclear if oral Baikal skullcap is beneficial in patients with Peyronie disease. Details: Observational research has found that taking oral Baikal skullcap root extract 150 mL twice daily for 6 months is associated with reduced time to disease stabilization, with an average reduction of 5 months, when compared with no treatment. In addition, 17% of patients taking Baikal skullcap had pain resolution and only 33% required surgical correction, compared with 0% and 58%, respectively, of control patients. In patients requiring surgery, taking Baikal skullcap did not appear to affect resolution; however, the study may have been inadequately powered to detect a difference between groups (105867).
• Prostate cancer. Although there has been interest in using oral Baikal skullcap for prostate cancer, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Psoriasis. Although there has been interest in using oral Baikal skullcap for psoriasis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Seizures. Although there has been interest in using oral Baikal skullcap for seizures, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral and intravenous Baikal skullcap for upper respiratory tract infections, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose. More evidence is needed to rate Baikal skullcap for these uses.

(Read more about BAIKAL SKULLCAP)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral hu zhang for allergic rhinitis, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Biliary disorders. Although there has been interest in using oral hu zhang for biliary disorders, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Constipation. Although there has been interest in using oral hu zhang for constipation, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Diabetes. Although there has been interest in using oral hu zhang for diabetes, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Gout. Although there has been interest in using oral hu zhang for gout, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Hepatitis. Although there has been interest in using oral hu zhang for hepatitis, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Menopausal symptoms. Although there has been interest in using oral hu zhang for menopausal symptoms, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Osteoarthritis. Although there has been interest in using oral hu zhang for osteoarthritis, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral hu zhang for RA, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Unstable angina. Oral hu zhang has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in patients hospitalized with unstable angina shows that taking hu zhang granules 7.5 grams and hawthorn granules 5 grams twice daily for 4 weeks, along with conventional therapy, improves quality of life and angina symptom scores, but does not reduce the frequency of angina attacks, when compared with conventional therapy alone (109610).
• Wound healing. Although there has been interest in using topical hu zhang for wound healing, there is insufficient reliable information about the clinical effects of hu zhang for this purpose. More evidence is needed to rate hu zhang for these uses.

(Read more about HU ZHANG)

POSSIBLY EFFECTIVE

• Alcohol use disorder. Oral kudzu seems to be beneficial for reducing alcohol consumption in heavy drinkers; however, it may not be beneficial in those with chronic alcohol use disorder. Details: Some research shows that heavy drinkers who take a specific kudzu root extract (Alkontrol-Herbal; NPI-031; Natural Pharmacia International, Inc.) 0.5-1 grams three times daily for 1-4 weeks consume less beer when given an opportunity to drink and may have more abstinent days (13085,92257). Other research shows that binge drinkers who take kudzu extract 2 grams as a single dose 2.5 hours prior to a 90-minute binge drinking episode consume 37% fewer beers than those taking placebo (92258). However, kudzu does not seem to decrease the craving for alcohol (10386,13085,57948,92257). Kudzu extract also does not seem to improve sobriety in people with chronic alcohol use disorder (10386).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there is interest in using oral kudzu for allergic rhinitis, there is insufficient reliable information about the clinical effects of kudzu for this condition.
• Angina. Although there is interest in using the injectable kudzu constituent puerarin for angina, there is insufficient reliable information about the clinical effects of oral kudzu for this condition.
• Angioplasty. Although there is interest in using the injectable kudzu constituent puerarin in patients undergoing percutaneous transluminal coronary angioplasty (PTCA), there is insufficient reliable information about the clinical effects of oral kudzu for this condition.
• Athletic performance. Oral kudzu has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in healthy males shows that taking capsules containing kudzu isoflavone extract 180 mg, soybean peptides 600 mg, taurine 200 mg, and ginseng saponins 120 mg daily in two divided doses for 15 days can significantly increase time to exhaustion during exercise when compared with placebo (57945).
• Back pain. Although there is interest in using the injectable kudzu constituent puerarin for back pain, there is insufficient reliable information about the clinical effects of oral kudzu for this condition.
• Cluster headache. Although there is interest in using oral kudzu for cluster headache, there is insufficient reliable information about the clinical effects of kudzu for this condition.
• Coronary heart disease (CHD). Although there is interest in using the injectable kudzu constituent puerarin for CHD, there is insufficient reliable information about the clinical effects of oral kudzu for this condition.
• Diabetes. It is unclear if oral kudzu is beneficial for diabetes. Details: Preliminary clinical research in adults with type 2 diabetes shows that taking oral puerarin, a kudzu constituent, 250 mg three times daily in addition to rosiglitazone 4 mg daily for 12 weeks reduces blood glucose levels and glycated hemoglobin (HbA1c) when compared to baseline (57951). The effect of kudzu alone is unclear. Additionally, the lack of a comparator group limits the validity of this finding.
• Diabetic nephropathy. It is unclear if oral kudzu is beneficial for diabetic nephropathy. Details: Preliminary clinical research in patients with diabetic nephropathy shows that taking puerarin, a kudzu constituent, 250 mg three times daily in addition to rosiglitazone 4 mg daily for 12 weeks improves laboratory measurements of kidney function, including serum creatinine, blood urea nitrogen, and urinary albumin, when compared to baseline (57951). The effect of kudzu alone is unclear. Additionally, the lack of a comparator group limits the validity of this finding.
• Hangover. Although there is interest in using oral kudzu for hangover, there is insufficient reliable information about the clinical effects of kudzu for this condition.
• Heart failure. Although there is interest in using the kudzu constituent puerarin for heart failure, there is insufficient reliable information about the clinical effects of kudzu for this condition.
• Hypertension. It is unclear if oral kudzu is beneficial for hypertension. Details: Preliminary clinical research in adults with hypertension shows that taking kudzu powder 1.5 grams twice daily for 12 weeks decreases systolic blood pressure by 16% and diastolic blood pressure by 12% when compared to baseline (92261). The validity of this finding is limited by the lack of a comparator group.
• Menopausal symptoms. Small clinical studies suggest that oral kudzu may modestly improve menopausal symptoms. Details: Preliminary clinical research shows that taking kudzu 25 mg, 50 mg, or 100 mg daily for 6 months during perimenopause improves climacteric symptoms based on a modified Green climacteric scale when compared with baseline (57890,57942). Other preliminary clinical research in patients with menopausal symptoms shows that taking kudzu extract 0.84-2.52 grams daily for 4 weeks, providing puerarin 113-338 mg daily, modestly reduces overall menopausal symptoms when compared with baseline (108154). The validity of the findings from these studies is limited by the lack of a comparator group. Other clinical research shows that taking kudzu 50 mg daily for 6 months during perimenopause reduces vasomotor symptoms similarly to taking conjugated equine estrogen 0.625 mg with or without medroxyprogesterone acetate 2.5 mg daily (57927).
• Migraine headache. It is unclear if oral kudzu is beneficial for migraine headache. Details: Preliminary clinical research in adults with migraine shows that taking one capsule of kudzu (Kuzik) daily, providing an unspecified dose of kudzu, for 90 days reduces the number of headache attacks per month by about 3, with approximately 50% of patients achieving a 50% reduction in monthly headache days when compared with baseline. There were also modest improvements in disability and medication use (108155). The validity of these findings is limited by the lack of a comparator group.
• Myocardial infarction (MI). Although there is interest in using the injectable kudzu constituent puerarin for MI, there is insufficient reliable information about the clinical effects of oral kudzu for this condition.
• Obesity. It is unclear if oral kudzu is beneficial for obesity. Details: Preliminary clinical research in adults with obesity shows that taking a kudzu extract 300 mg daily for 12 weeks reduces visceral fat and body mass index (BMI) when compared with placebo. However, doses of 200 mg do not seem to be as effective (57954).
• Postmenopausal conditions. It is unclear if oral or intravaginal kudzu is beneficial for postmenopausal conditions. Details: A small clinical study in postmenopausal individuals shows that taking kudzu containing isoflavones 100 mg orally once daily for 3 months improves flexible thinking and attention when compared with control. However, it does not appear to improve total cholesterol, low-density lipoprotein (LDL) cholesterol, or sex hormone levels (11386). Another small clinical study in postmenopausal individuals shows that taking kudzu 20 mg, 30 mg, or 50 mg daily for 24 weeks improves vaginal dryness and pH when compared with baseline, but not when compared with placebo. It also decreases a specific biomarker of bone turnover, called bone alkaline phosphatase, when compared with placebo (57924,57929). It is unclear if this correlates with improved bone density or with a reduced risk of osteoporosis. Kudzu has also been evaluated as an intravaginal gel. One small clinical study shows that applying 0.5 grams of kudzu 6% gel into the vagina every night for 2 weeks, followed by 3 nights each week for 9 weeks, improves vaginal symptoms of dryness, soreness, irritation, and abnormal discharge similarly to conjugated estrogen cream applied on the same schedule. However, kudzu gel is less effective than conjugated estrogen cream for improving overall vaginal health (96740). Another small clinical study of postmenopausal patients shows that applying 0.5 grams of kudzu 6% gel intravaginally every night for 3 weeks increases vaginal arterial blood flow and restores atrophic vaginal tissue when compared with placebo after 12 weeks (110702). In contrast, a similar study shows that applying 0.5 grams of kudzu 5% gel into the vagina every night for 2 weeks, followed by 3 nights each week for 10 weeks, does not improve vaginal symptoms when compared with placebo gel (105521). However, the study may have been inadequately powered to detect a difference between groups.
• Rhinosinusitis. Although there is interest in using oral kudzu for rhinosinusitis, there is insufficient reliable information about the clinical effects of kudzu for this condition.
• Stroke. Although there is interest in using the injectable kudzu constituent puerarin for stroke, there is insufficient reliable information about the clinical effects of oral kudzu for this condition. More evidence is needed to rate kudzu for these uses.

(Read more about KUDZU)

POSSIBLY EFFECTIVE

• Atopic dermatitis (eczema). Some clinical research suggests that topical licorice seems to improve symptoms of atopic dermatitis. Details: Applying gel formulations containing 1% or 2% licorice root extract three times daily for 2 weeks seems to reduce erythema by 35% to 61%, edema by 57% to 84%, and itching by 44% to 73%. The 2% gel seems to be more effective than the 1% gel (59732).
• Canker sores. Some clinical research suggests that topical licorice patches and mouth rinses seems to reduce ulcer size and pain in patients with recurrent aphthous stomatitis. Details: Clinical research shows that applying an oral patch containing licorice 0.015-0.229 mg/kg for 16 hours each day for 8 days does not affect ulcer healing time, but reduces ulcer size and post-stimulus pain, when compared with placebo (59769). A small clinical study also shows that applying bioadhesive hydrogel patches containing 1% licorice extract reduces the pain, as well as the diameter of necrosis and inflammatory halo of recurrent canker sores, when compared to baseline (59781). Mouth rinses containing licorice have also been used. One clinical study shows that swishing a diphenhydramine and 5% licorice extract solution around the mouth for about 3 minutes four times daily until the sores have healed reduces the average time to healing by 1.5 days when compared to a solution containing diphenhydramine alone. Pain was reduced by up to 69% more in those using licorice extract (104564). Another small clinical study shows that gargling with licorice extract four times daily for 2 days has a large beneficial effect on pain and ulcer size when compared with using a placebo gargle. The licorice extract was made by boiling licorice root 40 grams in one liter of water for 30 minutes and cooled (110319). In addition, preliminary clinical research shows that gargling with warm water containing deglycyrrhizinated licorice powder 200 mg four times daily for 7 days improves pain in 75% of patients by day one and results in complete healing in 75% of patients by day three (59857).
• Endotracheal intubation-related adverse effects. Some clinical research suggests that using licorice as a gargle or lozenge prior to endotracheal intubation can reduce adverse effects like sore throat and cough. Details: A meta-analysis of 5 clinical trials in patients undergoing elective surgical procedures shows that topical use of licorice, either as a gargle or lozenge, prior to endotracheal intubation reduces the risk for sore throat by 56% and reduces the risk for cough by 39% when compared with a control group at 24 hours post-extubation (100985). One clinical study included in this analysis shows that sucking on a single lozenge (Sualin, Hamdard Pharma) containing licorice extract 97 mg beginning 30 minutes prior to intubation reduces the risk for cough immediately after extubation by 56% when compared with a sugar candy lozenge. However, it doesn't seem to reduce cough at 30 minutes, 12 hours, or 24 hours post-extubation. This lozenge also appears to reduce the risk for sore throat by about 32% at 12 and 24 hours post-extubation, but not immediately or 30 minutes after extubation (25670). Additional clinical studies included in the meta-analysis show that gargling with fluid prepared with licorice 0.5 grams for at least one minute beginning 5 minutes prior to endotracheal intubation reduces the incidence and severity of post-extubation sore throat and coughing when compared with a water control (26464,59793).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Topical licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with mild to moderate acne associated with mask wearing shows that topical application of a combination of licorice root extract 0.3%, calendula 4%, and snail secretion filtrate 40% (AI complex) to the face twice daily for 12 weeks modestly reduces inflammatory, but not non-inflammatory or total, acne lesions when compared with placebo. There was no difference in overall treatment success, defined as at least almost clear skin or a large improvement (110322). It is unclear if any benefits are due to licorice, other ingredients, or the combination.
• Addison disease. Although there has been interest in using oral licorice for Addison disease, there is insufficient reliable information about the clinical effects of licorice for this condition.
• Adrenal insufficiency. Although there has been interest in using oral licorice for adrenal insufficiency, there is insufficient reliable information about the clinical effects of licorice for this condition.
• Allergic rhinitis (hay fever). It is unclear if using a licorice-containing nasal irrigation suspension improves symptoms in patients with allergic rhinitis. Details: A clinical study in patients with allergic rhinitis shows that using a nasal irrigation suspension containing licorice extract 900 mg daily for 1 month improves symptoms such as nasal blockage, rhinorrhea, sneezing, postnasal discharge, and olfactory disturbance when compared with baseline (108569). Although the study also utilized mometasone 2 mg nasal spray and isotonic saline nasal irrigation as comparators, symptom improvement was observed in all three groups, and there was no statistical comparison of outcomes between groups.
• Antipsychotic-induced hyperprolactinemia. Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in females with risperidone-induced hyperprolactinemia shows that taking a combination of licorice and peony (Peony-Glycyrrhiza Decoction; PGD) 45 grams daily for 4 weeks reduces prolactin levels to a similar extent as bromocriptine (59775). However, another study shows that taking the same product at the same dose for 16 weeks has no effect on prolactin levels in females with antipsychotic-induced hyperprolactinemia when compared with placebo. Although the prolactin-related adverse event questionnaire total score was moderately improved, there was no effect on clinically meaningful symptoms or menstrual resumption (97219). Both studies show no effect on psychotic symptoms (59775,97219). Preliminary clinical research in male patients with antipsychotic-induced hyperprolactinemia shows that taking an herbal extract containing licorice and peony (shakuyaku-kanzo-to) 2.5 grams three times daily reduces prolactin levels after 4 weeks, but does not have a significant effect on prolactin levels 4 weeks after treatment cessation (59907).
• Bleeding. Topical licorice might reduce bleeding when used in combination with other ingredients; its effect when used alone is unclear. Details: Some preliminary clinical research shows that topically applying 4 mL of a specific product (Ankaferd Blood Stopper, Mefar Ilaç Sanayi A.S.) containing licorice, Alpinia, thyme, stinging nettle, and common grape vine reduces bleeding, but does not improve the surgical time for episiotomy repair, when compared with saline (31010). Other preliminary clinical research shows that ampules of this same product placed in empty alveolus for up to 20 minutes reduces bleeding in postsurgical dental patients with increased bleeding tendency (31002).
• Cancer-related pain. It is unclear if oral licorice is beneficial for pain in patients with cancer. Details: Preliminary clinical research shows that taking a 1:1 combination of licorice root and peony root, along with a Taiwanese tonic vegetable soup comprised of lily bulb, lotus seed, and jujube fruit, reduces pain levels in terminal cancer patients when compared with patients consuming only the soup or the regular hospital diet (59770).
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral licorice for CFS, there is insufficient reliable information about the clinical effects of licorice for this condition.
• Colic. Although there has been interest in using oral licorice for colic, there is insufficient reliable information about the clinical effects of licorice for this condition.
• Coronavirus disease 2019 (COVID-19). Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients hospitalized in Egypt with moderate COVID-19 shows that administering oral licorice extract 300 mg (standardized to contain glycyrrhizin 60 mg) once daily and Boswellia serrata extract 300 mg twice daily for 14 days, along with following an institution-based COVID-19 treatment protocol, may modestly improve mortality and time to recovery when compared with patients receiving the standard protocol alone. The standard treatment protocol included acetaminophen, azithromycin, vitamin C, zinc, and enoxaparin (108579). It is unclear if any effect is due to licorice, Boswellia serrata, or the combination.
• Dental caries. It is unclear if oral licorice is beneficial for the prevention of dental caries. Details: One clinical study in adults shows that swishing 15 mL of a solution containing licorice extract 1% once nightly before bed for 5 days may reduce the acid production of cavity-causing bacteria, which may modestly reduce cavity risk, when compared with using a saline solution (108567). The validity of this study is limited by the short duration of treatment and follow-up.
• Dental plaque. It is unclear if licorice toothpaste or mouthwash is beneficial for reducing plaque. Details: Preliminary clinical research shows that using 0.25% or 0.50% glycyrrhizin-containing toothpaste twice daily does not reduce the amount of plaque, gingivitis, or bleeding in patients with proper dental hygienic measures when compared with the same toothpaste without glycyrrhizin (59812). Also, other preliminary clinical research shows that using glycyrrhizin-containing mouthwash for 3 days does not significantly reduce plaque levels (59855).
• Depression. It is unclear if adding oral licorice to standard treatment is beneficial for improving depression. Details: A very small, nonblinded clinical study in hospitalized adults with major depressive disorder shows that adding licorice extract 1400 mg daily, standardized to glycyrrhizin 7% to 8%, to standard treatment for 2 weeks improves depression rating scores when compared with baseline, although these improvements were numerically similar to those seen with standard treatment alone. Patients in the treatment group also took oral magnesium citrate 300 mg daily to prevent magnesium depletion. The validity of this finding is limited due to the small size of the study, short duration of treatment, and unclear reporting (108575).
• Diabetes. Although there has been interest in using oral licorice for diabetes, there is insufficient reliable information about the clinical effects of licorice for this condition.
• Dry mouth. It is unclear if rinsing the mouth with licorice is beneficial for dry mouth in people on hemodialysis. Details: Preliminary clinical research in hemodialysis patients with dry mouth shows that rinsing with a licorice mouthwash containing 8.34 grams of licorice concentrate per 500 mL of water with every meal for 10 days does not affect salivary flow rate, but reduces subjective feelings of dry mouth by about 28%, when compared with a water-based mouthwash and control group (97220).
• Dysmenorrhea. It is unclear if oral licorice is beneficial for reducing pain. Details: Preliminary clinical research shows that taking a syrup providing licorice extract 750 mg twice daily for the first 5 days of the menstrual cycle reduces pain as effectively as ibuprofen 400 mg every 8 hours in patients with moderate or severe dysmenorrhea (104558).
• Dyspepsia. Oral licorice might improve symptoms of dyspepsia when used in combination with other ingredients; its effect when used alone is unclear. Details: Various combination products manufactured by Steigerwald Arzneimittelwerk GmbH have been evaluated for dyspepsia. Two specific combination products containing licorice root (Iberogast; STW-5-S) seem to improve symptoms of dyspepsia. The combinations include licorice plus milk thistle, peppermint leaf, German chamomile, caraway, celandine, angelica, and lemon balm either with (Iberogast) or without clown's mustard plant (STW-5-S) 1 mL three times daily for 4 weeks (19532). A meta-analysis of studies using the Iberogast product shows that taking 1 mL orally three times daily over a period of 4 weeks reduces severity of acid reflux, epigastric pain, cramping, nausea, and vomiting when compared with placebo (13089). Also, using a preparation containing clown's mustard plant, German chamomile, peppermint, caraway, licorice, and lemon balm (STW 5-II) 1 mL three times daily for up to 12 weeks improves dyspepsia symptoms in 40% more patients when compared with placebo (12724).
• Familial Mediterranean fever. It is unclear if oral licorice is beneficial for familial Mediterranean fever. Details: Preliminary clinical research shows that taking a combination of licorice, andrographis, Siberian ginseng, and schisandra (ImmunoGuard, Inspired Nutritionals) four tablets three times daily for one month reduces the duration, frequency, and severity of attacks of familial Mediterranean fever in children when compared with placebo (12382). It is unclear if these effects are due to licorice, other ingredients, or the combination.
• Helicobacter pylori. It is unclear if oral licorice is beneficial for Helicobacter pylori eradication. Details: Some preliminary clinical research shows that adding licorice (D-Reglis, Iran Darouk Pharmaceutical Co.) 380 mg twice daily to conventional clarithromycin-based triple therapy for 14 days improves eradication rate by an additional 21% when compared with conventional treatment alone. However, any additional benefit might be limited to patients with peptic ulcer disease (97221). Other preliminary clinical research shows that taking a combination of licorice extract 100 mg and Lactobacillus paracasei HP7 in 150 mL of fermented milk daily for 8 weeks does not increase eradication rates when compared with fermented milk alone, although it may improve gastrointestinal symptom scores, decrease the gastric load of Helicobacter pylori, and improve some measures of inflammation when compared to baseline (100984).
• Hepatitis. Evidence for the use of intravenous licorice in the management of hepatitis B and C is mixed. Details: In some preliminary clinical research, a specific glycyrrhizin-containing intravenous preparation (Stronger Neominophagen C, Minophagen Pharmaceutical Co. Ltd.) appears to reduce mortality due to viral hepatitis by about 50% (3250). Other clinical research suggests that this same product reduces serum alanine aminotransferase (ALT) in hepatitis C patients but does not improve hepatitis C virus (HCV)-RNA levels (3247,59712,59721,59920). When used long-term, this preparation seems to reduce the risk of hepatocellular carcinoma in hepatitis C patients when compared to long-term use of other supplements, such as vitamin K (59905). This product has been used in various doses: 40 or 100 mL, containing 2 mg glycyrrhizin, 1 mg cysteine, and 20 mg of glycine per mL of solution, administered daily for 4-8 weeks, followed by 40 or 100 mL 2-7 times weekly for 2-16 weeks, has been used (3250,59905,59915); 40-120 mL diluted in 100 mL of 5% glucose solution and administered three times weekly for 4 weeks (59712,59721); 100 mL, which contained 200 mg glycyrrhizin, administered undiluted six times weekly for 4 weeks (59721); or 60 mL administered three times weekly for 16 weeks (59920). Other research shows that this preparation reduces ALT, aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) in patients with hepatitis B virus (59915). Oral licorice has not been evaluated for this purpose.
• Hypercholesterolemia. It is unclear if oral licorice is beneficial for improving cholesterol. Details: Preliminary clinical research shows that taking licorice root extract 0.1 grams daily for one month reduces plasma total cholesterol levels by 5%, plasma low-density lipoprotein (LDL) cholesterol levels by 9%, and plasma triglyceride levels by 14% when compared with baseline in patients with moderate hypercholesterolemia (59725). The validity of these findings is limited by the lack of a comparator group.
• Hyperkalemia. It is unclear if oral licorice is beneficial for reducing potassium levels. Details: Some clinical research in adults with diabetes and hypoaldosteronism suggests that taking glycyrrhizin 150 mg daily decreases potassium levels when compared with calcium polystyrene sulfonate (59897). Also, one very small clinical study in patients with anuria shows that taking glycyrrhetinic acid 1 gram daily for 2 weeks seems to decrease plasma potassium, but does not improve blood pressure, when compared with placebo (59723).
• IgA vasculitis. Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small retrospective study in patients aged 5-36 years with newly diagnosed IgA vasculitis shows that taking compound glycyrrhizin (Eisai Pharmaceutical Co, Ltd) three times daily along with loratadine, calcium, vitamin C, rutin, and other unspecified conventional treatments is associated with an improvement in cutaneous purpura symptoms and time to symptom regression when compared with placebo. After 1 month, the rate of complete resolution and time to regression in the treatment group was 82% and 5 days, respectively, compared with 65% and 8 days, respectively, in the placebo group. Compound glycyrrhizin contained glycyrrhizin, glycine, and methionine and was dosed by age, with a dose of 25 mg daily in those 12 years or younger and 50 mg daily in those over 12 years (108580).
• Irritable bowel syndrome (IBS). Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that a formulation containing licorice root, slippery elm bark, lactulose, and oat bran daily for 2 weeks improves stool consistency and increases bowel movement frequency by 20% in individuals with constipation-predominant IBS when compared to baseline. Symptoms of abdominal pain, bloating, straining, and global severity might also be reduced (35462). The validity of these findings is limited by the lack of a comparator group. Additionally, it is unclear if any benefits are due to licorice, other ingredients, or the combination.
• Lichen planus. It is unclear if intravenous licorice is beneficial for lichen planus. Details: A very small clinical study shows that intravenous administration of 0.2% glycyrrhizin solution, 40 mL daily for 4 weeks, improves clinical symptoms of oral lichen planus in a greater percentage of patients with chronic hepatitis C when compared with dental cleaning (59903). There is no evidence suggesting that oral licorice is beneficial.
• Liver cancer. Although there has been interest in using oral or intravenous licorice preparations for liver cancer, there is insufficient reliable information about the clinical effects of licorice for this condition.
• Melasma. Topical licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a topical cream (Clariderm Clear, Stiefel Laboratories Inc.) containing 7% licorice, emblica, and belides twice daily for 60 days is as effective as a cream containing 2% hydroquinone for lightening the skin in patients with melasma (59824). It is unclear if this effect is due to licorice, other ingredients, or the combination.
• Menopausal symptoms. It is unclear if oral licorice is beneficial for reducing hot flash frequency or severity. Details: In one preliminary clinical study, taking licorice root extract 330 mg orally three times daily for 8 weeks modestly reduces the frequency of hot flashes by about 1.3 per day and the severity of hot flashes by about 40% when compared with placebo (94659). However, another preliminary clinical study shows that taking a specific licorice root extract (D-Reglis, Iran Darouk Pharmaceutical Co.) 650 mg orally daily for 90 days does not reduce the number or severity of hot flashes when compared to baseline (25694).
• Muscle cramps. It is unclear if oral licorice is beneficial for muscle cramps due to cirrhosis or hemodialysis. Details: Preliminary clinical research shows that taking a specific combination of licorice and peony (shakuyaku-kanzo-to) might reduce muscle cramps in patients with hepatic cirrhosis or in patients undergoing hemodialysis when compared to baseline (13550,13551,13552). This combination was taken as 6-7.5 grams daily in up to three divided doses for 2-4 weeks in two studies (13550,13552). In a third study, the combination was taken as 2.5 grams during hemodialysis with self-administration at the onset of muscle cramping (13551).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral licorice is beneficial for NAFLD. Details: A small clinical trial in females with NAFLD shows that taking licorice extract (Shirin Darou Company, Shiraz, Iran) 500 mg twice daily for 12 weeks improves some measures of liver health and glycemic control when compared with placebo. Modest improvements occurred in levels of alanine aminotransferase, as well as in measures of insulin resistance and severity of liver steatosis based on ultrasonographic evaluation. There were no effects on body mass index (BMI), plasma lipids, fasting blood glucose, or other liver enzymes. All patients were also given weight loss and healthy lifestyle advice (110320). Preliminary clinical research shows that taking licorice root extract 2 grams daily for 2 months reduces liver function enzyme levels in patients with NAFLD when compared to pre-treatment (59841). It is unclear if this reduction is clinically significant.
• Obesity. It is unclear if oral licorice is beneficial for weight loss. Details: Preliminary clinical research shows that taking a specific licorice flavonoid oil (Glavonoid) 300 mg daily for 8 weeks has no effect on weight or body fat when compared with placebo in obese patients (17727).
• Oral mucositis. It is unclear if oral or topical licorice is beneficial for the prevention or treatment of chemotherapy- or radiation-induced oral mucositis. Details: In patients with head and neck cancer undergoing chemoradiation, preliminary clinical research shows that using oral and topical licorice powder twice daily in addition to conventional treatments for 6 weeks reduces the overall incidence of mucositis and also reduces the risk of developing severe oral mucositis to 15.5%, compared with 20% in those using topical honey and 43% in those using conventional treatments alone. Licorice treatment consisted of yastimadhu powder 5 grams mixed in honey for topical application in the mouth, as well as yastimadhu capsule 500 mg twice daily orally (104562). A small clinical trial in patients with head and neck cancer and oral mucositis currently undergoing radiation therapy shows that applying a mucoadhesive film containing licorice to the upper lip mucosal surface four times daily for 4 weeks, in conjunction with standard oral care, improves pain scores, mucositis grading, and ulcer size when compared with placebo film (108572). The validity of this finding is limited due to the short duration of treatment and exclusion of patients with severe mucositis.
• Osteoarthritis. Although there has been interest in using oral licorice for osteoarthritis, there is insufficient reliable information about the clinical effects of licorice for this condition.
• Osteoporosis. Although there has been interest in using oral licorice for osteoporosis, there is insufficient reliable information about the clinical effects of licorice for this condition.
• Parkinson disease. It is unclear if oral licorice is beneficial for improving Parkinson disease symptoms. Details: A small clinical study in patients with Parkinson disease shows that taking licorice extract 136 mg (containing glycyrrhizin 12.14 mg, polyphenols 136 mcg, and flavonoids 2.6 mcg) in a 5 mL syrup twice daily for 6 months improves Parkinson symptoms, tremor, and overall daily activities when compared with placebo (102961).
• Peptic ulcers. Evidence for the use of oral licorice for peptic ulcers is mixed. Details: There is some evidence that taking 6-12 tablets each containing deglycyrrhizinated licorice 380 mg, bismuth subnitrate 100 mg, aluminum hydroxide gel 100 mg, magnesium carbonate 200 mg, sodium bicarbonate 100 mg, and powdered alder buckthorn bark 30 mg (Caved-S, Cedona) in up to three divided doses daily for 4-16 weeks might accelerate the healing of peptic ulcers (11312,11313). Some clinical research also shows that this product is as effective as carbenoxolone sodium (Biogastrone) when taken at doses of two tablets three times daily after meals for 4 weeks (59871). In contrast, taking deglycyrrhizinated licorice (Ulcedal, Cedona, and others) 450-1000 mg three to five times daily for 4-8 weeks or glycyrrhizinic acid-reduced licorice 760 mg three times daily for 6 weeks does not seem to reduce the need for medication, pain, burning, or other discomfort in patients with peptic ulcers when compared with placebo (59864,59865,59873,59874).
• Physical performance. It is unclear if oral licorice is beneficial for improving physical performance in older females. Details: A small clinical trial in healthy females 59 years and older shows that taking licorice flavonoid oil 300 mg orally daily for 16 weeks in addition to strength training does not improve walking speed or other measures of functional mobility when compared with strength training alone (102960).
• Polycystic ovary syndrome (PCOS). Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking licorice root extract 2250 mg daily along with Ceylon cinnamon, levant berry, St. John's Wort, peony, and tribulus for 3 months with lifestyle modification improves symptoms of PCOS, including a reduction in oligomenorrhea/amenorrhea by 33% and the number of days between menstrual cycles by 43 days when compared with lifestyle modification alone. Although conception rate increased 4-fold in the intervention group, live birth rate was similar between groups (97216). The effect of licorice alone for the treatment of PCOS is unknown.
• Prostate cancer. Although there has been interest in using oral licorice for prostate cancer, there is insufficient reliable information about the clinical effects of licorice for this condition.
• Psoriasis. It is unclear if topical licorice is beneficial for improving psoriasis symptoms. Details: Preliminary clinical research shows that using a topical cream containing licorice extract and milk proteins twice daily for 4 weeks does not reduce the duration of corticosteroid cream therapy in patients with palmar and/or plantar psoriasis, but may improve skin peeling, the area of skin affected, and some subjective symptoms, when compared with corticosteroid cream alone (59823).
• Systemic lupus erythematosus (SLE). Although there has been interest in using oral licorice for SLE, there is insufficient reliable information about the clinical effects of licorice for this condition.
• Tuberculosis. Although there has been interest in using oral licorice for tuberculosis, there is insufficient reliable information about the clinical effects of licorice for this condition.
• Urticaria. Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of clinical research in adults with chronic urticaria shows that taking compound glycyrrhizin, containing glycyrrhizin, N-acetyl cysteine, and glycine, as 50-75 mg three times daily along with desloratadine 5-8.8 mg daily for 4 weeks improves response rate, cure rate, and recurrence rate when compared with desloratadine alone (108571). However, most studies included in the meta-analysis were low quality, and all studies were conducted in China. Higher quality studies in other geographic locations are needed to confirm these findings.
• Vitiligo. It is unclear if the licorice constituent compound glycyrrhizin is beneficial for vitiligo. Details: A meta-analysis of 14 clinical studies in patients aged 3-68 years old with vitiligo shows that taking licorice constituent compound glycyrrhizin 25-75 mg 3 times daily for 2-6 months with standard treatment improves effectiveness, cure rate, and immune-mediated inflammatory markers when compared with standard treatment alone (112232). More evidence is needed to rate licorice for these uses.

(Read more about LICORICE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. It is unclear if oral stevia is beneficial in patients with diabetes; the available research is conflicting. Details: A small single-dose study shows that taking stevia leaf extract 1000 mg, standardized to contain 91% stevioside, along with a meal reduces postprandial glucose levels by 18% in adults with type 2 diabetes when compared with a starch control (11812). However, clinical research in patients with type 1 or type 2 diabetes shows that taking stevioside 250 mg three times daily for 3 months does not affect blood glucose levels or glycated hemoglobin (HbA1C) when compared with baseline (16705). Also, a small clinical study in patients with diabetes shows that drinking 200 mL of black tea, sweetened with stevia extract 2%, three times daily for 8 weeks does not affect glycemic indices when compared with drinking tea sweetened with sucralose (103695).
• Hypertension. It is unclear if oral stevia is beneficial in patients with hypertension; the available research is conflicting. Details: Some clinical research in patients with mild to moderate hypertension shows that taking stevioside, a constituent of stevia, 750-1500 mg in three divided doses daily reduces systolic blood pressure by 10-14 mmHg and diastolic blood pressure by 6-14 mmHg within one week to three months of treatment initiation and continuing for up to 2 years (11809,11810). However, other clinical research in patients with mild hypertension shows that taking stevioside in doses up to 15 mg/kg daily does not significantly reduce blood pressure (16706).
• Obesity. It is unclear if oral stevia is beneficial in patients with obesity; the available research is conflicting. Details: Although a small clinical study in healthy adults shows that drinking water with stevia (Truvia) 245 ppm as a single dose reduces appetite and energy intake when compared with drinking water alone (103697), other small, single-dose studies have shown no effect of stevia 15.3 mg or 1 gram as a single dose on satiety, energy intake, or fullness when compared with either water alone or a non-nutritive sweetener (103696,110124). A small clinical study in healthy adults shows that taking an aqueous stevia leaf extract (SweetLeaf) twice daily for 12 weeks does not affect body weight, compared with an increase in weight in the control group. This suggests that stevia extract may have attenuated weight gain in this study (106458). More evidence is needed to rate stevia for these uses.

(Read more about STEVIA)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Oral Baikal skullcap 0.5-3.52 grams daily has been used with apparent safety for up to 8 weeks (92776,101738,101739,110023). However, a high quality assessment of safety has not been conducted. A specific product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been associated with an increased risk for liver and lung injury. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination. There is insufficient reliable information available about the safety of Baikal skullcap when used intravenously or topically.

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

(Read more about BAIKAL SKULLCAP)

There is insufficient reliable information available about the safety of hu zhang.

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

(Read more about HU ZHANG)

POSSIBLY SAFE ...when used orally and appropriately. Kudzu appears to be safe for up to 4 months (10386,11386,92257). ...when used intravaginally and appropriately. Kudzu 5% to 6% gel has been used with apparent safety for up to 12 weeks (96740,105521,110702).

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

(Read more about KUDZU)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Licorice has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes. Licorice flavonoid oil 300 mg daily for 16 weeks, and deglycyrrhizinated licorice products in doses of up to 4.5 grams daily for up to 16 weeks, have been used with apparent safety (6196,11312,11313,17727,100984,102960). ...when licorice products containing glycyrrhizin are used orally in low doses, short-term. Licorice extract 272 mg, containing glycyrrhizin 24.3 mg, has been used daily with apparent safety for 6 months (102961). A licorice extract 1000 mg, containing monoammonium glycyrrhizinate 240 mg, has been used daily with apparent safety for 12 weeks (110320). In addition, a syrup providing licorice extract 750 mg has been used twice daily with apparent safety for 5 days (104558). ...when applied topically. A gel containing 2% licorice root extract has been applied to the skin with apparent safety for up to 2 weeks. (59732). A mouth rinse containing 5% licorice extract has been used with apparent safety four times daily for up to one week (104564).

POSSIBLY UNSAFE ...when licorice products containing glycyrrhizin are used orally in large amounts for several weeks, or in smaller amounts for longer periods of time. The European Scientific Committee on Food recommends that a safe average daily intake of glycyrrhizin should not exceed 10 mg (108577). In otherwise healthy people, consuming glycyrrhizin daily for several weeks or longer can cause severe adverse effects including pseudohyperaldosteronism, hypertensive crisis, hypokalemia, cardiac arrhythmias, and cardiac arrest. Doses of 20 grams or more of licorice products, containing at least 400 mg glycyrrhizin, are more likely to cause these effects; however, smaller amounts have also caused hypokalemia and associated symptoms when taken for months to years (781,3252,15590,15592,15594,15596,15597,15599,15600,16058)(59731,59740,59752,59785,59786,59787,59792,59795,59805,59811)(59816,59818,59820,59822,59826,59828,59849,59850,59851,59867)(59882,59885,59888,59889,59895,59900,59906,97213,110305). In patients with hypertension, cardiovascular or kidney conditions, or a high salt intake, as little as 5 grams of licorice product or 100 mg glycyrrhizin daily can cause severe adverse effects (15589,15593,15598,15600,59726).

PREGNANCY: UNSAFE
when used orally. Licorice has abortifacient, estrogenic, and steroid effects. It can also cause uterine stimulation. Heavy consumption of licorice, equivalent to 500 mg of glycyrrhizin per week (about 250 grams of licorice per week), during pregnancy seems to increase the risk of delivery before gestational age of 38 weeks (7619,10618). Furthermore, high intake of glycyrrhizin, at least 500 mg per week, during pregnancy is associated with increased salivary cortisol levels in the child by the age of 8 years. This suggests that high intake of licorice during pregnancy may increase hypothalamic-pituitary-adrenocortical axis activity in the child (26434); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about LICORICE)

LIKELY SAFE ...when certain stevia constituents, including stevioside and rebaudiosides A, D, and M, are used orally as sweeteners in foods. These constituents have generally recognized as safe (GRAS) status in the US for this purpose (16699,16700,16702,16705,16706,108049). The stevia constituent stevioside has been safely used in doses of up to 1500 mg daily for 2 years (11809,11810,11811). There is insufficient reliable information available about the safety of whole stevia or stevia extracts when used orally. The European Food Safety Authority (EFSA) has determined that the acceptable intake of steviol glycosides is 4 mg/kg daily (106456); however, it is unclear how this relates to the use of whole stevia or stevia extract.

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

(Read more about STEVIA)

ALCOHOL (Ethanol) Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol.  Details In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might increase the risk of bleeding when used concomitantly with anticoagulant and antiplatelet drugs.  Details Preliminary clinical research suggests that taking capsules containing a combination of astragalus, goldthread, and Baikal skullcap daily for 4 weeks inhibits platelet aggregation; the effect seems to be similar to that of aspirin 50 mg daily (33075). It is unclear if this effect is due to Baikal skullcap, other ingredients, or the combination.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of Baikal skullcap with antidiabetes drugs might enhance blood glucose lowering effects.  Details Baicalein, a constituent of Baikal skullcap, has alpha-glucosidase inhibitory activity in vitro (6292). Animal research also suggests that Baikal skullcap enhances the antidiabetic effects of metformin (33408). However, in a small human study, taking Baikal skullcap extract did not enhance the antidiabetic effects of metformin, although it did modestly lower glucose levels during an oral glucose tolerance test (OGTT) (101738). Until more is known, use cautiously.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Baikal skullcap with antihypertensive drugs might have additive effects and increase the risk of hypotension.  Details Animal research suggests that baicalein, a constituent of Baikal skullcap, might lower blood pressure (33374).

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Baikal skullcap and antithyroid drugs may result in additive activity and increase the risk of hypothyroidism.  Details In an animal hyperthyroid model, Baikal skullcap improved levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) (101736). The clinical significance of this effect is unclear.

CNS DEPRESSANTS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties.  Details In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap may increase levels of drugs metabolized by CYP1A2 enzymes.  Details In vitro evidence suggests that constituents of Baikal skullcap inhibit the activity of CYP1A2 (33346,33484). 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, Baikal skullcap might increase levels of drugs metabolized by CYP2C19 enzymes.  Details In vitro evidence suggest that wogonin, a constituent of Baikal skullcap, modestly inhibits the activity of CYP2C19 enzymes (33484). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of large amounts of Baikal skullcap might interfere with hormone replacement therapy, due to competition for estrogen receptors.  Details In vitro evidence suggests that Baikal skullcap has estrogenic activity (16061).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might reduce lithium excretion and increase serum levels of lithium.  Details Baikal skullcap is thought to have diuretic properties, which may reduce lithium excretion (5541). The dose of lithium might need to be decreased.

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, Baikal skullcap might alter the levels and clinical effects of OATP substrates.  Details Some pharmacokinetic research shows that baicalin, a constituent of Baikal skullcap, can decrease plasma levels of rosuvastatin. The mechanism is thought to involve stimulation of the activity of the organic anion-transporting polypeptide 1B1 (OATP1B1), which transports rosuvastatin into the liver. This decreases plasma levels of the drug, but increases levels at the site of action in the liver. The degree to which rosuvastatin levels are affected depends on the OATP1B1 haplotype of the individual (16395). Baikal skullcap might also affect other OATP1B1 substrates (16396,16397,16398).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might increase levels of drugs transported by P-glycoprotein.  Details In vitro and animal research suggests that baicalein, oroxylin A, and wogonin, constituents of Baikal skullcap, can inhibit P-glycoprotein (33372,33395,33440,33462). This effect has not been reported in humans.

(Read more about BAIKAL SKULLCAP)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details Hu zhang contains the constituent resveratrol. Resveratrol seems to have antiplatelet effects (2949,2950,2951,2952,2961,70813,70828,70831,70892,70968,71106).

CARBAMAZEPINE (Tegretol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase the effects and adverse effects of carbamazepine.  Details In animals, blood and tissue levels of carbamazepine were increased when given in combination with hu zhang. It is thought that increased levels of carbamazepine are due to cytochrome P450 3A4 (CYP3A4) inhibition (101418). This interaction has not been reported in humans.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP1A1.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1A1 enzyme (70862,70811). This interaction has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP1A2.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1A2 enzyme (21733). This interaction has not been reported in humans.

CYTOCHROME P450 1B1 (CYP1B1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP1B1.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1B1 enzyme (70834). This interaction 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, hu zhang might increase levels of drugs metabolized by CYP2C19.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP2C19 enzyme (70896). This interaction 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, hu zhang might increase levels of drugs metabolized by CYP2E1.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP2E1 enzyme (7864,70896). Also, a pharmacokinetic study shows that taking resveratrol 500 mg daily for 10 days prior to taking a single dose of chlorzoxazone 250 mg increases the maximum concentration of chlorzoxazone by about 54%, the area under the curve of chlorzoxazone by about 72%, and the half-life of chlorzoxazone by about 35% (95824). Chlorzoxazone is used as a probe drug for CYP2E1.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP3A4.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP3A4 enzyme (7864,70896). However, a clinical study in adults with NAFLD found that adding resveratrol 3000 mg daily for 8 weeks did not necessitate dose adjustments to any established medications metabolized by CYP3A4 (91327).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might competitively inhibit the effects of estrogen replacement therapy.  Details In vitro research shows that hu zhang might have estrogenic activity (13124,16061).

(Read more about HU ZHANG)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, kudzu may increase the risk of bleeding if used with antiplatelet or anticoagulant drugs.  Details Kudzu isoflavones are reported to have antiplatelet activity (13278,13291).

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, taking kudzu with antidiabetes drugs might increase the risk of hypoglycemia.  Details Kudzu might lower blood glucose levels and have additive effects in patients treated with antidiabetic agents (13285,13292,57868,57951). The dose of diabetes medications might need to be adjusted.

CAFFEINE Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking kudzu with caffeine might increase levels of caffeine.  Details In healthy males injected with the kudzu constituent puerarin, caffeine clearance and metabolism is inhibited (23583). This effect has been attributed to inhibition of cytochrome P450 1A2 (CYP1A2) enzyme, which is involved in caffeine metabolism. It is unclear if taking kudzu orally would have this same effect.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, kudzu might alter the effects of estrogen therapy.  Details Some research suggests that kudzu has estrogenic effects (11386,57874,57877). This may enhance or inhibit the effects of estrogen therapy.

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might have additive hepatotoxic effects.  Details There is some concern that kudzu can adversely affect the liver (88777,92259,92260,92262).

METHOTREXATE (Trexall, others) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking kudzu with methotrexate might increase the risk of methotrexate toxicity.  Details Preclinical research suggests that kudzu extract greatly reduces the elimination and increases the toxicity of methotrexate. Kudzu might inhibit organic anion transporters (OATs) that are responsible for hepatobiliary and renal excretion of anions, similar to the interaction between methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) (13296).

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, kudzu might interfere with tamoxifen activity.  Details Some research suggests that kudzu may have estrogenic effects (11386,110702).

(Read more about KUDZU)

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, licorice might reduce the effects of antihypertensive drugs.  Details In human research, licorice increases blood pressure in a dose-dependent manner (1372,7620,59877).

CISPLATIN (Platinol-AQ) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, licorice might reduce the effects of cisplatin.  Details In animal research, licorice diminished the therapeutic efficacy of cisplatin (59763).

CORTICOSTEROIDS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of licorice and corticosteroids might increase the side effects of corticosteroids.  Details Case reports suggest that concomitant use of licorice and oral corticosteroids, such as hydrocortisone, can potentiate the duration of activity and increase blood levels of corticosteroids (3252,12672,20040,20042,48429,59756). Additionally, in one case report, a patient with neurogenic orthostatic hypertension stabilized on fludrocortisone 0.1 mg twice daily developed pseudohyperaldosteronism after recent consumption of large amounts of black licorice (108568).

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, licorice might increase levels of drugs metabolized by CYP2B6.  Details In vitro research shows that licorice extract and glabridin, a licorice constituent, inhibit CYP2B6 isoenzymes (10300,94822). Licorice extract from the species G. uralensis seems to inhibit CYP2B6 isoenzymes to a greater degree than G. glabra extract in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2B6; however, these interactions have not yet 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, licorice might increase levels of drugs metabolized by CYP2C19.  Details In vitro, licorice extracts from the species G. glabra and G. uralensis inhibit CYP2C19 isoenzymes in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C19; however, this interaction has not yet been reported in humans.

CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, licorice might increase levels of drugs metabolized by CYP2C8.  Details In vitro, licorice extract from the species G. glabra and G. uralensis inhibits CYP2C8 isoenzymes (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C8; however, this interaction has not yet 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, licorice might increase or decrease levels of drugs metabolized by CYP2C9.  Details There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes (10300,94822). However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity (14441). Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.  Details Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity (59808). Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity (14441). However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species (10300,94822). Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of licorice with digoxin might increase the risk of cardiac toxicity.  Details Overuse or misuse of licorice with cardiac glycoside therapy might increase the risk of cardiac toxicity due to potassium loss (10393).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of licorice with diuretic drugs might increase the risk of hypokalemia.  Details Overuse of licorice might compound diuretic-induced potassium loss (10393,20045,20046,59812). In one case report, a 72-year-old male with a past medical history of hypertension, type 2 diabetes, hyperlipidemia, arrhythmia, stroke, and hepatic dysfunction was hospitalized with severe hypokalemia and uncontrolled hypertension due to pseudohyperaldosteronism. This was thought to be provoked by concomitant daily consumption of a product containing 225 mg of glycyrrhizin, a constituent of licorice, and hydrochlorothiazide 12.5 mg for 1 month (108577).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, licorice might increase or decrease the effects of estrogen therapy.  Details Theoretically, licorice might interfere with estrogen therapy due to estrogenic and anti-estrogenic effects (7860,16058).

LOOP DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.  Details Theoretically, loop diuretics might enhance the mineralocorticoid effects of licorice by inhibiting the enzyme that converts cortisol to cortisone; however, bumetanide (Bumex) does not appear to have this effect (3255).

METHOTREXATE (Trexall, others) Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, licorice might increase levels of methotrexate.  Details Animal research suggests that intravenous administration of glycyrrhizin, a licorice constituent, and high-dose methotrexate may delay methotrexate excretion and increase systemic exposure, leading to transient elevations in liver enzymes and total bilirubin (108570). This interaction has not yet been reported in humans.

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, licorice might decrease levels of midazolam.  Details In humans, the licorice constituent glycyrrhizin appears to moderately induce the metabolism of midazolam (59808). This is likely due to induction of cytochrome P450 3A4 by licorice. Until more is known, licorice should be used cautiously in people taking midazolam.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.  Details In vitro research shows that licorice can increase P-glycoprotein activity (104561).

PACLITAXEL (Abraxane, Onxol) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, licorice might decrease plasma levels and clinical effects of paclitaxel.  Details Multiple doses of licorice taken concomitantly with paclitaxel might reduce the effectiveness of paclitaxel. Animal research shows that licorice 3 grams/kg given orally for 14 days before intravenous administration of paclitaxel decreases the exposure to paclitaxel and increases its clearance. Theoretically, this occurs because licorice induces cytochrome P450 3A4 enzymes, which metabolize paclitaxel. Notably, a single dose of licorice did not affect exposure or clearance of paclitaxel (102959).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, licorice might decrease plasma levels and clinical effects of warfarin.  Details Licorice seems to increase metabolism and decrease levels of warfarin in animal models. This is likely due to induction of cytochrome P450 2C9 (CYP2C9) metabolism by licorice (14441). Advise patients taking warfarin to avoid taking licorice.

(Read more about LICORICE)

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, stevia might increase the risk for hypoglycemia when combined with antidiabetes drugs.  Details Preliminary clinical research in patients with type 2 diabetes suggests that taking a single dose of stevia extract 1000 mg reduces postprandial blood glucose levels when taken with a meal (11812). However, other clinical research in patients with type 1 or type 2 diabetes suggests that taking stevioside 250 mg three times daily does not significantly affect blood glucose levels or glycated hemoglobin (HbA1C) after three months of treatment (16705).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining stevia or stevia constituents with antihypertensive agents might increase the risk of hypotension.  Details Stevia extract and stevioside might lower blood pressure in patients with hypertension (3745,3747,5031,11809,11810). However, other clinical research suggests that stevioside does not significantly lower blood pressure in patients with hypertension (16706).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, stevia might decrease clearance and increase levels of lithium.  Details Animal research suggests that stevia extracts might have diuretic activity (3746,3747). Theoretically, increased reabsorption of lithium along with sodium might reduce excretion and increase levels of lithium.

(Read more about STEVIA)

General ...Orally, Baikal skullcap seems to be well-tolerated. There is currently a limited amount of information on the adverse effects of intravenous and topical Baikal skullcap.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, erythema, nausea, pruritus, and vomiting.
Intravenously: Skin reactions.
Topically: Dermatitis.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity and hypersensitivity pneumonitis have been reported with a specific combination product (Limbrel, Primus Pharmaceuticals) containing extracts of Baikal skullcap and catechu.

Cardiovascular ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, elevated triglyceride levels occurred in 1 of 10 patients who received 400 mg every 8 hours and 2 of 10 patients treated with 600 mg every 8 hours, compared with 0 of 10 patients who received 200 mg every 8 hours and 0 of 6 patients who received placebo. Triglyceride elevations were considered mild and resolved after discontinuation (110023).

Dermatologic ...Orally, taking Baikal skullcap may cause erythema and pruritus (105867). Intravenously, Baikal skullcap as part of a Tanreqing injection has been associated with reports of skin reactions in some pediatric patients (96281).
Topically, several cases of allergic contact dermatitis have been reported after applying sunscreen containing Baikal skullcap extract (105869,105870). Allergic contact dermatitis has also been reported after applying a facial cream (Resveratrol BE, Skinceuticals) containing Baikal skullcap root extract 0.5% and resveratrol 1%. Patch testing identified a positive reaction to both ingredients (110024). Baikal skullcap-induced dermatitis appears to respond to treatment with a topical corticosteroid and calcineurin inhibitor (105870).

Gastrointestinal ...Orally, use of Baikal skullcap has been associated with epigastric pain, abdominal pain, constipation, diarrhea, nausea, and vomiting (101738,105867).

Hepatic ...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of acute liver damage. There have been at least five published reports of liver damage associated with this product. In all cases, the patients were females aged 54-68 years taking doses of 250-500 mg twice daily for 1-3 months. Signs and symptoms included jaundice, pruritus, abdominal pain, fever, rash, and elevated serum bilirubin and liver transaminase levels. All patients fully recovered and levels normalized within 3 months after discontinuation (18009,96282). In addition to these published case reports, approximately 30 liver-related adverse events have been reported to the manufacturer of this product (18009). The mechanism of hepatotoxicity is unclear (18009,18010); it is estimated that the incidence of hepatotoxicity with this product is around 1 in 10,000, although the actual incidence is unknown (18010). In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.
Hepatotoxicity has also been reported in two patients taking a specific dietary supplement (Move Free Advanced, Reckitt Benckiser) containing Baikal skullcap, black catechu, glucosamine, chondroitin, and hyaluronic acid (33460) and in a patient taking Baikal skullcap, elderflower, horseradish, and white willow (101737). The investigators determined that the hepatotoxicity was likely caused by Baikal skullcap in these cases (33460,101737). Additionally, cases of liver injury are reported in 4 of 37 patients taking various Kampo formulations containing Baikal skullcap and other herbs daily. Patients presented with elevated liver function tests 7 to 38 days after consumption (112179). It is unclear if this adverse effect is from Baikal skullcap, other ingredients, or the combination.
In a small study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, liver transaminase elevations occurred in 2 of 10 patients who received 400 mg every 8 hours for 6 days, compared with 0 of 6 patients who received placebo. No patients receiving either 200 mg or 600 mg every 8 hours experienced liver transaminase elevations. The elevations were considered mild and resolved after discontinuation (110023).

Pulmonary/Respiratory ...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of hypersensitivity pneumonitis. Symptoms include fever, chills, headache, cough, chronic bronchitis, shortness of breath, weight loss, and fatigue. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.

Renal ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, proteinuria of undefined severity occurred in 1 of 10 patients who received 200 mg every 8 hours for 6 days, 3 of 10 patients who received 400 mg every 8 hours for 6 days, and 5 of 10 patients who received 600 mg every 8 hours for 6 days, compared with 1 of 6 patients who received placebo. The proteinuria was considered mild and resolved after discontinuation (110023).

(Read more about BAIKAL SKULLCAP)

General ...There is currently a limited amount of information on the adverse effects of hu zhang.

(Read more about HU ZHANG)

General ...Orally and intravaginally, kudzu seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Elevated liver transaminases.

Cardiovascular ...Orally, side effects of kudzu reported in clinical trials have included palpitations and chest discomfort; however, these effects did not occur more frequently than with placebo (57924,57927).

Dermatologic ...Orally, a side effect of kudzu reported in one clinical trial has included urticaria; however, this effect did not occur more frequently than with placebo (57924). There is one case report of allergic reaction following use of a combination herbal product (Kakkonto) containing kudzu involving a maculopapular eruption starting on the thighs and spreading over the entire body (13111,57886).

Gastrointestinal ...Orally, some side effects of kudzu reported in clinical trials have included nausea, dyspepsia, and bloating; however, these effects did not occur more frequently than with placebo (57927,57942).

Genitourinary ...Intravaginally, irritation of the vulva has been reported with kudzu gel. These cases were generally mild and transient (110702).

Hematologic ...Intravenously, the kudzu derivative, puerarin, has caused intravascular hemolysis (13298,15025,57947).

Hepatic ...Orally, there are several cases reports of liver injury following use of kudzu involving elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (88777,92260).

Neurologic/CNS ...Orally, a side effect of kudzu reported in one clinical trial has included dizziness; however, this effect did not occur more frequently than with placebo (57924).

Other ...Orally, a side effect of kudzu reported in one clinical trial has included mastodynia; however, this effect did not occur more frequently than with placebo (57942).

(Read more about KUDZU)

General ...Orally, licorice is generally well tolerated when used in amounts commonly found in foods. It seems to be well tolerated when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes or when used topically, short-term.
Most Common Adverse Effects:
Orally: Headache, nausea, and vomiting.
Topically: Contact dermatitis.
Intravenously: Diarrhea, itching, nausea, and rash.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about acute renal failure, cardiac arrest, cardiac arrhythmias, hypertension, hypokalemia, muscle weakness, paralysis, pseudohyperaldosteronism, and seizure associated with long-term use or large amounts of licorice containing glycyrrhizin.

Cardiovascular ...Orally, excessive licorice ingestion can lead to pseudohyperaldosteronism, which can precipitate cardiovascular complications such as hypertension and hypertensive crisis, ventricular fibrillation or tachycardia, sinus pause, and cardiac arrest. These effects are due to the licorice constituent glycyrrhizin and usually occur when 20-30 grams or more of licorice product is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,97213) (104563,108574,108576,110305,112234). In one case report, an 89-year-old female taking an herbal medicine containing licorice experienced a fatal arrhythmia secondary to licorice-induced hypokalemia. The patient presented to the hospital with recurrent syncope, weakness, and fatigue for 5 days after taking an herbal medicine containing licorice for 2 months. Upon admission to the hospital, the patient developed seizures, QT prolongation, and ventricular arrhythmia requiring multiple defibrillations. Laboratory tests confirmed hypokalemia and pseudohyperaldosteronism (112234).
However, people with cardiovascular or kidney conditions may be more sensitive, so these adverse events may occur with doses as low as 5 grams of licorice product or glycyrrhizin 100 mg daily (15589,15593,15598,15600,59726). A case report in a 54-year-old male suggests that malnutrition might increase the risk of severe adverse effects with excessive licorice consumption. This patient presented to the emergency room with cardiac arrest and ventricular fibrillation after excessive daily consumption of licorice for about 3 weeks. This caused pseudohyperaldosteronism and then hypokalemia, leading to cardiovascular manifestations. In spite of resuscitative treatment, the patient progressed to kidney failure, refused dialysis, and died shortly thereafter (103791).

Dermatologic ...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912). There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578). Burning sensation, itching, redness, and scaling were reported rarely in patients applying a combination of licorice, calendula, and snail secretion filtrate to the face. The specific role of licorice is unclear (110322).
In rare cases, the glycyrrhizin constituent of licorice has caused rash and itching when administered intravenously (59712).

Endocrine ...Orally, excessive licorice ingestion can cause a syndrome of apparent mineralocorticoid excess, or pseudohyperaldosteronism, with sodium and water retention, increased urinary potassium loss, hypokalemia, and metabolic alkalosis due to its glycyrrhizin content (781,10619,15591,15592,15593,15594,15595,15596,15597,15598)(15600,16057,16835,25659,25660,25673,25719,26439,59818,59822)(59832,59864,91722,104563,108568,108574,110305,112234). These metabolic abnormalities can lead to hypertension, edema, EKG changes, fatigue, syncope, arrhythmias, cardiac arrest, headache, lethargy, muscle weakness, dropped head syndrome (DHS), rhabdomyolysis, myoglobinuria, paralysis, encephalopathy, respiratory impairment, hyperparathyroidism, and acute kidney failure (10393,10619,15589,15590,15593,15594,15596,15597,15599)(15600,16057,16835,25660,25673,25719,26439,31562,59709,59716)(59720,59740,59787,59820,59826,59882,59889,59900,91722,97214,100522) (104563,108576,108577). These effects are most likely to occur when 20-30 grams of licorice products containing glycyrrhizin 400 mg or more is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,108574). However, some people may be more sensitive, especially those with hypertension, diabetes, heart problems, or kidney problems (15589,15593,15598,15600,59726,108576,108577) and even low or moderate consumption of licorice may cause hypertensive crisis or hypertension in normotensive individuals (1372,97213). The use of certain medications with licorice may also increase the risk of these adverse effects (108568,108577). One case report determined that the use of large doses of licorice in an elderly female stabilized on fludrocortisone precipitated hypokalemia and hypertension, requiring inpatient treatment (108568). Another case report describes severe hypokalemia necessitating intensive care treatment due to co-ingestion of an oral glycyrrhizin-specific product and hydrochlorothiazide for 1 month (108577). Glycyrrhetinic acid has a long half-life, a large volume of distribution, and extensive enterohepatic recirculation. Therefore, it may take 1-2 weeks before hypokalemia resolves (781,15595,15596,15597,15600). Normalization of the renin-aldosterone axis and blood pressure can take up to several months (781,15595,108568). Treatment typically includes the discontinuation of licorice, oral and intravenous potassium supplementation, and short-term use of aldosterone antagonists, such as spironolactone (108574,108577).
Chewing tobacco flavored with licorice has also been associated with toxicity. Chewing licorice-flavored tobacco, drinking licorice tea, or ingesting large amounts of black licorice flavored jelly beans or lozenges has been associated with hypertension and suppressed renin and aldosterone levels (12671,12837,97214,97215,97217,108574). One case report suggests that taking a combination product containing about 100 mg of licorice and other ingredients (Jintan, Morishita Jintan Co.) for many decades may be associated with hypoaldosteronism, even up to 5 months after discontinuation of the product (100522). In another case report, licorice ingestion led to hyperprolactinemia in a female (59901). Licorice-associated hypercalcemia has also been noted in a case report (59766).

Gastrointestinal ...Nausea and vomiting have been reported rarely following oral use of deglycyrrhizinated licorice (25694,59871). Intravenously, the glycyrrhizin constituent of licorice has rarely caused gastric discomfort, diarrhea, or nausea (59712,59915).

Immunologic ...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912). There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578).

Musculoskeletal ...In a case report, excessive glycyrrhizin-containing licorice consumption led to water retention and was thought to trigger neuropathy and carpal tunnel syndrome (59791).

Neurologic/CNS ...Orally, licorice containing larger amounts of glycyrrhizin may cause headaches. A healthy woman taking glycyrrhizin 380 mg daily for 2 weeks experienced a headache (59892). Intravenously, the glycyrrhizin constituent of licorice has rarely caused headaches or fatigue (59721). In a case report, licorice candy ingestion was associated with posterior reversible encephalopathy syndrome accompanied by a tonic-clonic seizure (97218).

Ocular/Otic ...Orally, consuming glycyrrhizin-containing licorice 114-909 grams has been associated with transient visual loss (59714).

Pulmonary/Respiratory ...Orally, large amounts of licorice might lead to pulmonary edema. In one case report, a 64-year old male consumed 1020 grams of black licorice (Hershey Twizzlers) containing glycyrrhizin 3.6 grams over 3 days, which resulted in pulmonary edema secondary to pseudohyperaldosteronism (31561). Intravenously, the glycyrrhizin constituent of licorice has caused cold or flu-like symptoms, although these events are not common (59712,59721).

(Read more about LICORICE)

General ...Orally, stevia and steviol glycosides appear to be well tolerated. Most minor adverse effects seem to resolve after the first week of use.
Most Common Adverse Effects:
Abdominal bloating, dizziness, headache, myalgia, nausea, and numbness.
Serious Adverse Effects (Rare):
Allergic reactions.

Gastrointestinal ...Orally, stevia and steviol glycosides such as stevioside, can cause gastrointestinal adverse effects such as abdominal fullness and nausea. However, these generally resolve after the first week of use (11809,11810).

Immunologic ...Theoretically, stevia might cause allergic reactions in individuals sensitive to plants in the Asteraceae/Compositae family (11811). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Musculoskeletal ...Orally, stevia and steviol glycosides may cause myalgia, but this generally resolves after the first week of use (11809,11810).

Neurologic/CNS ...Orally, stevia and steviol glycosides may cause headache, dizziness, and numbness (11809,11810).

(Read more about STEVIA)