Oat Combination by Genestra Brands

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)

POSSIBLY EFFECTIVE

• Bleeding. Intramuscular motherwort injections, alone or in combination with standard treatment such as oxytocin, might reduce volume of blood loss and duration of bleeding after vaginal delivery, caesarian section, or induced abortion. Details: In females with postpartum bleeding after vaginal birth, most research shows that adding motherwort injection to oxytocin or carboprost treatment is more effective than those treatments alone. A meta-analysis of 29 low quality trials shows that injection with motherwort 40-140 mg, in addition to varying doses of oxytocin, is more effective than oxytocin alone for reducing blood loss after vaginal delivery (101890). This combination reduces the mean blood loss within 2 and 24 hours of delivery by 55 mL and 85 mL, respectively. Also, the risk of postpartum hemorrhage, defined as an estimated blood loss of at least 400 mL within 2 hours or at least 500 mL within 24 hours, is reduced by 71%, based on meta-analysis of 18 trials. Meta-analysis of 8 trials also shows motherwort alone to be more effective than oxytocin for reducing blood loss within 24 hours of delivery, but not within 2 hours of delivery. Meta-analysis of 4 trials shows that motherwort 40-200 mg is as effective as oxytocin for reducing the risk of postpartum hemorrhage (101890). Studies were all very low to low quality, with moderate to high risk of bias, and conducted in China, the latter of which limits generalizability to other geographic regions. In females with post-caesarian bleeding, adding motherwort injection to oxytocin reduces blood loss and the rate of post-partum hemorrhage when compared with using oxytocin alone. In a large clinical trial, motherwort 40 mg was injected into the uterus during the caesarian section, followed by 20 mg intramuscular injections every 12 hours over the next 36 hours. However, motherwort injection into the uterus does not seem to be more effective than oxytocin for reducing bleeding during the caesarian section (94203). However, a meta-analysis of 8 trials shows that prophylactic injection with motherwort 60-200 mg, in addition to carboprost 250 mcg, reduces the mean blood loss within 2 and 24 hours of delivery by 127 mL and 147 mL, respectively, with a 72% decrease in the incidence of postpartum hemorrhage over carboprost alone (101891). In 7 of the 8 trials the mode of delivery was caesarian section and 1 was a vaginal delivery. A large observational study suggests that intramuscular injection of motherwort into the uterus combined with intravenous oxytocin is associated with a lower risk of post-partum hemorrhage after caesarian section when compared with intravenous oxytocin plus intramuscular injection of oxytocin into the uterus (112291). A meta-analysis of 9 clinical trials among patients undergoing induced abortion shows that motherwort injection combined with oxytocin lowers the volume of blood loss both 2 hours and 24 hours after the procedure when compared with oxytocin alone (112292). However, motherwort alone is not more effective than oxytocin for blood loss post-abortion. Meta-analysis indicates that motherwort injected alone or with oxytocin reduces the duration of blood loss compared with oxytocin or no treatment. Studies were primarily of very low quality, and all studies were conducted in China, limiting generalizability to other populations and geographic locations.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. Oral motherwort has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in males experiencing alcohol withdrawal syndrome with disordered sleep, anxiety, and irritability shows that a single dose of a combination product containing motherwort 50 mg, valerian 170 mg, hops 50 mg, and lemon balm 50 mg, taken 1 hour before bedtime, improves sleep quality and decreases awakenings when compared with placebo (63884).
• Amenorrhea. Although there has been interest in using oral motherwort for amenorrhea, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Anxiety. It is unclear if oral motherwort is beneficial in patients with anxiety. Details: Preliminary clinical research in adults with anxiety and hypertension shows that taking a specific preparation of motherwort extracted in soybean oil (Farmagen Ltd.) 600 mg orally twice daily for 28 days reduces anxiety and depression scores when compared with baseline. A significant improvement occurred in 32% of subjects, and a moderate improvement occurred in 48% of subjects (94209). The validity of this finding is limited by the lack of a comparator group.
• Arrhythmia. Although there has been interest in using oral motherwort for arrhythmia, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Asthma. Although there has been interest in using oral motherwort for asthma, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Cancer. Although there has been interest in using oral motherwort for cancer, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Dysmenorrhea. Although there has been interest in using oral motherwort for dysmenorrhea, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Flatulence. Although there has been interest in using oral motherwort for flatulence, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Heart failure. Although there has been interest in using oral motherwort for heart failure, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Herpes zoster (shingles). Although there has been interest in using topical motherwort for herpes zoster, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Hypertension. It is unclear if oral motherwort is beneficial in patients with hypertension. Details: Preliminary clinical research in adults with hypertension and anxiety shows that taking a specific preparation of motherwort extracted in soybean oil (Farmagen Ltd.) 600 mg orally twice daily for 28 days reduces blood pressure when compared with baseline. In subjects with mild hypertension, systolic and diastolic blood pressure decreased by 10% and 11%, respectively. In subjects with more severe hypertension, systolic and diastolic blood pressure decreased by 7% and 11%, respectively (94209). The validity of this finding is limited by the lack of a comparator group.
• Hyperthyroidism. Although there has been interest in using oral motherwort for hyperthyroidism, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Insomnia. Although there has been interest in using oral motherwort for insomnia, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Menopausal symptoms. Oral motherwort has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with menopause shows that taking a combination of motherwort, burdock, dong quai, licorice root, and wild yam three times daily for 12 weeks reduces the number and severity of menopausal symptoms, such as hot flashes, sleep problems, mood changes, and vaginal dryness, in 71% of patients, compared with 17% of patients taking a placebo (48522).
• Pruritus. Although there has been interest in using topical motherwort for pruritus, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Wound healing. Although there has been interest in using topical motherwort for wound healing, there is insufficient reliable information about the clinical effects of motherwort for this purpose. More evidence is needed to rate motherwort for these uses.

(Read more about MOTHERWORT)

LIKELY EFFECTIVE

• Coronary heart disease (CHD). A diet high in soluble fiber, such as that found in oats, reduces the risk of CHD. Details: Clinical research shows that a diet containing foods high in fiber, such as oats, oat bran, or whole oat flour, reduces the risk of CHD (2737,4960,4962,4963,4964,4965,4966,4967,4968). In 1993, the US Food and Drug Administration (FDA) approved a health claim stating that consuming at least 3 grams of soluble fiber per day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of CHD (102336). However, clinical studies show that at least 3.6 grams of soluble fiber daily is needed to reduce the risk of CHD (5786,5787,5788,5794,5795,5796).
• Hypercholesterolemia. A diet rich in soluble fiber, such as that found in oats, can reduce cholesterol by a moderate amount. Details: Oats, oat bran, and other soluble fibers can modestly reduce total and low-density lipoprotein (LDL) cholesterol when consumed as part of a diet low in saturated fat. Consuming 56-150 grams of whole oat products such as oatmeal and oat bran, containing 3.6-10 grams of soluble fiber daily, can significantly lower total and LDL cholesterol levels. For each gram of soluble fiber consumed, total cholesterol decreases by about 1.4 mg/dL and LDL by about 1.2 mg/dL. Eating 3-10 grams of soluble fiber daily can reduce total cholesterol by about 4-14 mg/dL (4976,4977,5786,5788,5792,5794,5795,8521,107749); however, doses greater than 10 grams daily don't seem to increase effectiveness (5788). Eating three bowls of oatmeal (28 gram servings) daily can decrease total cholesterol by about 5 mg/dL (4972,4973,4974,4975,4976,4977,5786,5788,6188). Oat bran products, such as oat bran muffins and oat bran flakes, may vary in their ability to lower cholesterol, depending on the total soluble fiber content and other dietary variables (6188). Whole oat products might be more effective for lowering LDL and total cholesterol than foods containing oat bran plus soluble fiber (10145).

POSSIBLY EFFECTIVE

• Diabetes. A diet rich in whole grains, such as oats, may help prevent diabetes or improve blood glucose control in patients with type 1, type 2, or gestational diabetes. Details: Population research shows that for every 16 gram daily serving of whole grains, including oats, there is a 7% to 11% lower risk of developing type 2 diabetes (100622). There is also evidence that consuming oats can decrease blood glucose and insulin levels, as well as lipid levels, in patients with diabetes. The glycemic effects of oats depend on the level of processing of the oat products. Consuming intact oat kernels or thick-cut oats (>0.6 mm) reduces postprandial blood glucose and insulin, but consuming thin-cut, or "quick", oats has no effect (105536). Clinical research shows that consuming oats and oat bran for 4-8 weeks decreases pre-prandial blood glucose, 24-hour plasma glucose, glycated hemoglobin (HbA1c), insulin levels, and low-density lipoprotein (LDL) cholesterol in people with type 2 diabetes (4980,4982,6266,103345). Various doses have been used, including 3 grams of soluble fiber daily, or bread providing 34 grams of total fiber daily (9 grams of soluble fiber) (4961,4980). Additional clinical research in obese adults with type 2 diabetes shows that eating whole grain oats 50-100 grams daily in place of other carbohydrates reduces postprandial blood glucose by 19-27 mg/dL when compared with other carbohydrates in a healthy diet. After 1 year, the groups consuming 50 grams and 100 grams of oats had an additional 0.48% and 0.64% reduction in HbA1c, respectively, when compared with the regular healthy diet group (97520). There is also some evidence that consuming oats 50 grams daily, containing 25 grams of soluble fiber, might be more effective for improving glycemic control and decreasing hyperinsulinemia than the standard moderate fiber diet recommended by the American Diabetes Association (ADA) (6266). Oats have also been evaluated in adolescents with type 1 diabetes. One very small clinical study shows that taking 50 grams of a specific oat product (Betaglucare), providing beta-glucans 6 grams, in three divided doses daily for one week is beneficial for glycemic control and variability when compared with a standard diet without beta-glucans or with taking only 25 grams of the product daily. Maximal, mean, and pre- and post-meal blood glucose levels were modestly lower, and minimal blood glucose levels were modestly higher. Most measures of glycemic variability were statistically different, although there were no differences in the duration of hypoglycemia or hyperglycemia between groups (105261). Oats have also been evaluated in patients with gestational diabetes. A randomized, controlled trial shows that taking 30 grams of a specific oat bran product (OAB; Golden Light Cup Company) orally twice daily at lunch and dinner for 4 weeks improves mean fasting blood glucose and two-hour postprandial glucose when compared with a control group. After 4 weeks, the mean fasting blood glucose and 2-hour postprandial glucose in the treatment group were 85 mg/dL and 104 mg/dL, respectively, compared with 93 mg/dL and 117 mg/dL, respectively, in the control group (107751). The validity of this study is limited by the short treatment duration and lack of follow-up.
• Gastric cancer. A diet rich in soluble fiber, such as that found in oats, might reduce the risk of gastric cancer. Details: Observational research has found that consuming a diet that includes cereal fiber, such as oats and oat bran, might reduce the incidence of gastric cancer (10435).

POSSIBLY INEFFECTIVE

• Colorectal cancer. Regular consumption of oats does not seem to reduce the risk of colorectal cancer. Details: Observational research has found that consuming oat bran or oats orally doesn't seem to reduce the risk of colon cancer. Additionally, consuming fiber, including oat-bran fiber, is not associated with a reduction in the risk for recurrence of colorectal adenomas (4820,5104).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using topical oats for acne, there is insufficient reliable information about the clinical effects of oats for this purpose.
• Anxiety. Although there is interest in using oral oats for anxiety, there is insufficient reliable information about the clinical effects of oats for this purpose.
• Atopic dermatitis (eczema). Topical colloidal oatmeal cream may be beneficial in patients with atopic dermatitis. Details: Preliminary clinical research shows that applying a cream containing colloidal oatmeal 1% daily for 2 weeks has a moderate effect on the severity of atopic dermatitis when compared with baseline (103344). The validity of this finding is limited by the lack of a comparator group. Other research suggests that colloidal oatmeal may be beneficial when used in combination with topical steroids. Clinical research shows that the benefits obtained from applying an ointment containing fluocinolone 0.025% to the hands for 2 weeks were better maintained in the patients who also used a cream containing colloidal oatmeal 1% during this time period and for an additional 4 weeks when compared with patients using fluocinolone and the cream base without colloidal oatmeal. Quality of life was also improved in the patients using colloidal oatmeal (103340).
• Breast cancer. Observational research suggests that regular oatmeal intake may be associated with reduced mortality from breast cancer. Details: Population research in postmenopausal patients has found that those who have eaten 50 grams of oatmeal daily prior to a breast cancer diagnosis have a 20% reduced risk of all-cause mortality in the 7 years following the diagnosis when compared with patients who have not eaten oatmeal. However, no benefit was seen when post-diagnostic oatmeal intakes were examined (103343).
• Burns. Although there is interest in using topical oats for burns, there is insufficient reliable information about the clinical effects of oats for this purpose.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral oats for CFS, there is insufficient reliable information about the clinical effects of oats for this purpose.
• Cognitive function. It is unclear if oral oats are beneficial in healthy adults with mild memory impairment. Details: Preliminary clinical research in healthy middle-aged adults with self-reported memory decline shows that consuming a specific wild green-oats extract (Neuravena, Frutarom) 800 mg as a single dose improves overall speed, but not overall accuracy, of cognitive performance when compared with placebo. However, a higher dose of 1600 mg was ineffective (97519).
• Dry skin. It is unclear if applying lotion containing colloidal oat extract improves dry skin to a greater extent than other lotion products. Details: Preliminary clinical research shows that applying a lotion containing colloidal oat extract (Aveeno Active Naturals Skin Relief 24Hr Moisturizing Lotion, Johnson & Johnson) twice daily for 2 weeks improves itchiness, cracking, scaling, dryness, and roughness when compared to baseline in females with dry skin (91458). Additional preliminary clinical research shows that applying a colloidal oatmeal lotion to the legs twice daily for three weeks reduces skin dryness and improves skin integrity when compared to baseline in adults with dry skin (97518). The validity of these findings is limited by the lack of a comparator group.
• Exercise-induced muscle soreness. It is unclear if oral oats are beneficial for exercise-induced muscle soreness. Details: A small clinical trial shows that eating two cookies containing oat flour 60 grams daily for 8 weeks reduces muscle soreness 48 or 72 hours after downhill running when compared with baseline (103341).
• Fat redistribution syndrome. It is unclear if oral oats are beneficial for fat redistribution syndrome. Details: Consumption of a high fiber diet, including oats, with adequate energy and protein might prevent fat deposition in patients with HIV. A one-gram increase in total dietary fiber may decrease the risk of fat deposition by 7% (12517).
• Gallbladder disease. Although there is interest in using oral oats for gallbladder disease, there is insufficient reliable information about the clinical effects of oats for this purpose.
• Hypertension. It is unclear if oral oats are beneficial for hypertension. Details: Observational research has found that consumption of oats as oatmeal or oat cereal does not seem to reduce diastolic blood pressure (DBP) or systolic blood pressure (SBP) in males with minor elevations in blood pressure (2956). A randomized, controlled trial in patients with stage 1 hypertension receiving dietary guidance shows that taking 30 grams of oat bran, providing 8.9 grams of dietary fiber, once daily with breakfast or in between meals for 3 months improves various blood pressure measures when compared with dietary guidance alone. After 3 months of treatment, 24-hour maximum SBP and DBP decreased by 14 mmHg and 11 mmHg, respectively, and office SBP and DBP decreased by 15 mmHg and 10 mmHg, respectively. Oat consumption may also have impacted antihypertensive medication use. Two patients in the control group increased doses of antihypertensive medications, whereas 6 patients in the treatment group decreased doses and 1 patient discontinued use (107750). The effect of oral oat bran on patients with stage 2 hypertension or pre-hypertension is unknown.
• Irritable bowel syndrome (IBS). Although there is interest in using oral oats for IBS, there is insufficient reliable information about the clinical effects of oats for this purpose.
• Metabolic syndrome. Limited research suggests that oats may not be beneficial for metabolic syndrome. Details: Preliminary clinical research in adults with metabolic syndrome shows that adding oat bran 40 grams daily for 6 weeks to a low-calorie diet does not reduce the incidence of metabolic syndrome. Oat bran also does not improve body weight, blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, or blood glucose levels when compared with a low-calorie diet alone in patients with metabolic syndrome (103342).
• Osteoarthritis. Although there is interest in using oral oats for osteoarthritis, there is insufficient reliable information about the clinical effects of oats for this condition.
• Pruritus. Applying oat lotion topically may improve some types of pruritus. Details: Preliminary clinical research shows that applying an oat lotion (Espanol) twice daily for up to 2 weeks can decrease itching intensity by about 20% when compared to baseline in patients with pruritus associated with chronic kidney disease (uremic pruritus). This decrease is similar to the effects of applying vinegar 5% solution or taking hydroxyzine 10 mg orally. However, applying the oat lotion does not appear to decrease the frequency of itching (91457).
• Psoriasis. Although there is interest in using topical oats for psoriasis, there is insufficient reliable information about the clinical effects of oats for this purpose.
• Rheumatoid arthritis (RA). Although there is interest in using oral oats for RA, there is insufficient reliable information about the clinical effects of oats for this purpose.
• Stroke. It is unclear if oral oats are beneficial for reducing the risk of stroke. Details: Population research suggests that consuming oatmeal for breakfast once weekly might reduce the incidence of stroke by a small amount when compared with consuming white bread or eggs for breakfast (103337).
• Ulcerative colitis. Oral oats have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific oat-based product (Profermin, Nordisk Rebalance) containing fermented oat flour, Lactobacillus plantarum, barley malt flour, and lecithin, 250 mL orally twice daily for 8 weeks, reduces disease activity and increases remission in about two-fold more patients with relapsing ulcerative colitis, when compared with treatment with a specific nutritional beverage (Fresubin Original, Fresenius Kabi) (90271).
• Wound healing. Although there is interest in using topical oats for wound healing, there is insufficient reliable information about the clinical effects of oats for this purpose. More evidence is needed to rate oats for these uses.

(Read more about OATS)

POSSIBLY EFFECTIVE

• Anxiety. Oral passion flower has a long history of use as a sedative and may improve symptoms of anxiety in some patients. Details: Preliminary clinical research shows that taking a specific dried alcoholic extract of passion flower (Sedanxio, Tilman SA) 400 mg orally twice daily for 2-8 weeks reduces the severity of non-specific anxiety when compared to baseline (88198). The validity of this finding is limited by the lack of a placebo group. Passionflower has also been evaluated as an adjunct to conventional medication. One clinical small study in patients with generalized anxiety disorder shows that taking a specific passion flower extract (Pasipay, Iran Darouk Pharmaceutical Company) 15 drops three times daily along with sertraline 50-100 mg daily for one month reduces anxiety when compared with taking sertraline alone (95036). Passion flower has also been compared to conventional treatments. One preliminary clinical study shows that taking passion flower extract 90-180 mg daily reduces symptoms of non-specific anxiety when compared to baseline, and seems to be comparable to taking mexazolam (15391). A small clinical study in patients with generalized anxiety disorder shows that taking a specific passion flower extract (Pasipay, Iran Darouk Pharmaceutical Company) 45 drops orally once daily for 28 days reduces anxiety similarly to oxazepam 30 mg daily. However, passion flower appears to have a slower onset of action than oxazepam (8007). This finding is limited because it did not utilize a therapeutic dosing regimen for oxazepam, which is given 3-4 times daily to account for its short half-life. Passion flower has also been studied in combination with other ingredients. A small clinical study in healthy adults shows that taking a combination of herbal extracts containing passion flower 40 mg, valerian root, black horehound, and hawthorn (Euphytose, Bayer HealthCare) 6 times daily with meals for 14 days reduces anxiety and sympathetic and autonomic nervous system activation in response to a psychosocial stressor when compared with placebo (111222). It is unclear if these effects are due to valerian, other ingredients, or the combination.
• Pre-procedural anxiety. Oral passion flower modestly reduces preoperative anxiety. Details: Two small clinical studies in adults awaiting dental surgery or inguinal hernia repair surgery shows that taking a specific passion flower extract (Pasipay, Iran Darouk Pharmaceutical Company) reduces preoperative anxiety when compared with placebo. Passion flower extract was given as 20 drops or 500 mg 90 minutes prior to surgery, with or without another dose on the evening before surgery (88195,88196). Another small clinical study shows that drinking 5 mL of syrup containing passion flower aqueous extract (Passiflora syrup, Sandoz) 700 mg orally 30 minutes before epidural catheter insertion for inguinal hernia repair surgery seems to attenuate anxiety; the placebo group experienced a significant increase in anxiety (88194). This finding is limited because there were no statistical comparisons conducted between groups. Passion flower has also been compared with conventional medications. Three clinical studies show that taking passion flower prior to dental surgery decreases preoperative anxiety similarly to oral midazolam 15 mg. One study used passion flower 260 mg, administered 30 minutes prior to the surgery (95038), the second used 500 mg, administered 60 minutes prior (104206), and the third used 600 mg, administered 45 minutes prior (110014). Of the two studies that evaluated patient preference, patients in one study preferred midazolam, possibly due to its ability to cause perioperative amnesia (95038), whereas there was no preference in the other study (110014). Another clinical study shows that taking passion flower 1000 mg one hour prior to elective minor or moderate surgery reduces preoperative anxiety similarly to melatonin 6 mg; however, passion flower seems to cause more cognitive impairment than melatonin (95037).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Adjustment disorders. Oral passion flower has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in patients with adjustment disorder with anxious mood shows that taking two tablets of a specific combination product (Euphytose, Bayer Healthcare) three times daily seems to decrease anxiety symptoms when compared with placebo. One tablet contains the dry extracts of passion flower 40 mg, valerian 40 mg, hawthorn 10 mg, and black horehound 10 mg, as well as the caffeine-containing stimulant herbs kola nut 15 mg and guarana 15 mg (6250). It is unclear if this effect is due to passion flower, other ingredients, or the combination.
• Alcohol use disorder. Oral passion flower has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults experiencing alcohol withdrawal symptoms shows that taking one capsule of a combination product (Relief) three times daily for 15 days reduces the frequency of excessive sweating, reduces serum liver enzyme levels, and improves appetite and quality of life when compared to baseline. One capsule contains passion flower extract 30 mg, black seed extract 100 mg, cocoa extract 90 mg, radish extract 165 mg, and saffron extract 15 mg (97280). The validity of these findings is limited by the lack of a comparator group.
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral passion flower is beneficial in patients with ADHD. Details: A small clinical trial in children aged 6-13 years with ADHD shows that taking tablets of passion flower (Pasipay, Iran Darouk Pharmaceutical Company) 0.02 mg/kg orally twice daily for 8 weeks reduces parent and teacher ratings of ADHD symptoms no better than taking methylphenidate (0.5 mg/kg twice daily) (88197).
• Benzodiazepine withdrawal. It is unclear if oral passion flower is beneficial for benzodiazepine withdrawal. Details: A moderate-sized observational study in adults with depression or anxiety on antidepressants undergoing a benzodiazepine taper after chronic benzodiazepine use suggests that taking a specific dry extract of passion flower (Tractana, Baldacci) 200-600 mg daily for 3 months is associated with a faster benzodiazepine dose reduction and greater percentage of patients with at least 50% reduction or complete benzodiazepine discontinuation after 1 and 3 months from taper initiation when compared with control (111651). The validity of these effects is limited by a lack of placebo group and the retrospective observational study design.
• Congestive heart failure (CHF). Oral passion flower has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with mild CHF shows that taking a combination of passion flower and hawthorn extracts 2 mL three times daily for 6 weeks increases six-minute walking distance when compared with placebo. However, it does not appear to improve exercise capacity on a bicycle ergometer test (19201). It is unclear if this effect is due to passion flower, hawthorn, or the combination. Additionally, hawthorn has been evaluated alone for the management of CHF, with some research suggesting that although it may improve symptoms, it may also be associated with worsened clinical outcomes.
• Fibromyalgia. Although there is interest in using oral passion flower for fibromyalgia, there is insufficient reliable information about the clinical effects of passion flower for this condition.
• Insomnia. Small clinical studies suggest that oral passion flower may modestly improve sleep quality in patients with insomnia and poor sleep quality. Details: Some preliminary clinical research in adults with insomnia shows that taking passion flower extract 60 mg every evening before bedtime for 2 weeks increases total sleep time by around 23 minutes, but doesn't seem to improve sleep efficiency, sleep latency, or awakening after sleep onset, when compared with placebo (102866). Another smaller clinical study in young adults with mild fluctuations in sleep quality shows that drinking tea prepared by steeping passion flower aerial parts 2 grams in 250 mL of boiling water for 10 minutes every evening, about an hour before bedtime for 7 nights, improves subjective ratings of sleep quality, but not other sleep parameters, when compared with placebo (parsley tea) (17374). Passion flower has also been studied in combination with other ingredients. One small clinical study in adults with primary insomnia shows that taking a specific combination product containing passion flower 80 mg, valerian 300 mg, and hops 30 mg (NSF-3, M/s Tablets India) orally at bedtime for 2 weeks yields similar effects on subjective measures of sleep as zolpidem 10 mg nightly (88193).
• Menopausal symptoms. Although there is interest in using oral passion flower for menopausal symptoms, there is insufficient reliable information about the clinical effects of passion flower for this purpose.
• Muscle cramps. Although there is interest in using oral passion flower for muscle cramps, there is insufficient reliable information about the clinical effects of passion flower for this purpose.
• Neuropathic pain. Although there is interest in using oral passion flower for neuropathic pain, there is insufficient reliable information about the clinical effects of passion flower for this condition.
• Opioid withdrawal. It is unclear if oral passion flower helps to prevent opioid withdrawal. Details: A small preliminary clinical study in adults who are completing an inpatient withdrawal program for opioid addiction shows that taking passion flower liquid extract 60 drops, in combination with clonidine 0.8 mg daily, is better than clonidine alone when used for reducing symptoms such as anxiety, irritability, insomnia, and agitation. However, the combination is no better than clonidine alone for reducing physical symptoms such as tremor and nausea (2303).
• Seizures. Although there is interest in using oral passion flower for seizures, there is insufficient reliable information about the clinical effects of passion flower for this condition.
• Stress. Oral passion flower has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy adults shows that taking a specific combination product (Relaxane, Max Zeller Söhne AG) containing passion flower 90 mg, lemon balm 50 mg, valerian 90 mg, and butterbur 90 mg three times daily for 3 days modestly reduces subjective anxiety scores during social stress testing when compared with placebo or no treatment (97276). It is unclear if this effect is due to passion flower, other ingredients, or the combination. More evidence is needed to rate passion flower for these uses.

(Read more about PASSION FLOWER)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral skullcap for allergic rhinitis (hay fever), there is insufficient reliable information about the clinical effects of skullcap for this purpose.
• Anxiety. It is unclear if oral skullcap is beneficial for reducing symptoms of anxiety. Details: Preliminary clinical research shows that healthy people who take a single dose of freeze-dried skullcap extract 100-350 mg feel more relaxed when compared to baseline. This effect appears to last for about 2 hours (12216). However, other preliminary clinical research in healthy patients shows that taking freeze-dried skullcap (Skullcap, Eclectic Institute) 350 mg three times daily for 2 weeks does not reduce anxiety scores when compared with placebo (91690). Because these were short-term studies in healthy patients, it's unclear if skullcap is beneficial in anxiety disorders or if extended use is beneficial.
• Atherosclerosis. Although there has been interest in using oral skullcap for atherosclerosis, there is insufficient reliable information about the clinical effects of skullcap for this purpose.
• Contact dermatitis. Although there has been interest in using oral skullcap for contact dermatitis, there is insufficient reliable information about the clinical effects of skullcap for this purpose.
• Epilepsy. Although there has been interest in using oral skullcap for epilepsy, there is insufficient reliable information about the clinical effects of skullcap for this purpose.
• Hyperlipidemia. Although there has been interest in using oral skullcap for hyperlipidemia, there is insufficient reliable information about the clinical effects of skullcap for this purpose.
• Insomnia. Although there has been interest in using oral skullcap for insomnia, there is insufficient reliable information about the clinical effects of skullcap for this purpose.
• Premenstrual dysphoric disorder (PMDD). Although there has been interest in using oral skullcap for PMDD, there is insufficient reliable information about the clinical effects of skullcap for this purpose.
• Spasticity. Although there has been interest in using oral skullcap for spasticity, there is insufficient reliable information about the clinical effects of skullcap for this purpose.
• Stress. Although there has been interest in using oral skullcap for stress, there is insufficient reliable information about the clinical effects of skullcap for this purpose.
• Stroke. Although there has been interest in using oral skullcap for stroke, there is insufficient reliable information about the clinical effects of skullcap for this purpose. More evidence is needed to rate skullcap for this use.

(Read more about SKULLCAP)

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)

POSSIBLY SAFE ...when used orally and appropriately. A motherwort extract in soybean oil has been used with apparent safety at doses of 1200 mg daily for up to 28 days (94209) ...when administered intramuscularly, short-term. One or more intramuscular injections have been used with apparent safety in total combined doses of 40-200 mg over 48 hours or less to prevent and/or stop postpartum bleeding (94203,101890,101891,101892). Post-marketing surveillance of over 8000 females found that a specific motherwort product (Chengdu No 1 Pharma Company Ltd) has been used without significant adverse effects for a duration of 48 hours or less (104855) ...when administered by intrauterine injection, short-term. Post-marketing surveillance of over 1800 patients found that a specific motherwort product (Chengdu No 1 Pharma Company Ltd) has been used without significant adverse effects for a duration of 48 hours or less (104855).

PREGNANCY: LIKELY UNSAFE
when used orally or by injection. Alkaloids present in motherwort have uterine stimulant effects (4,12,19).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about MOTHERWORT)

LIKELY SAFE ...when used orally and appropriately in food amounts (4960,4969,5792,5797). Oat bran has Generally Recognized as Safe (GRAS) status in the US (4912). Whole grain oats 50-100 grams daily have been used for up to 1 year without serious adverse effects (97520).

POSSIBLY SAFE ...when used topically and appropriately (12). Lotion containing colloidal oat 1% has been used topically without adverse effects for up to 6 weeks (97518,103340). There is insufficient reliable information available about the safety of oats when used orally in medicinal amounts.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts (5792,5797).

(Read more about OATS)

LIKELY SAFE ...when used orally as a flavoring in foods. The US Food and Drug Administration (FDA) lists passion flower as a permitted food flavoring additive, to be used in the minimum quantity necessary (91203).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Passion flower extract has been used with apparent safety at doses up to 800 mg daily for up to 8 weeks (88198,102866). A specific passion flower extract (Pasipay, Iran Darouk Pharmaceutical Company) has been safely used at a dose of 45 drops daily for up to one month (8007,95036). Also, a tea prepared by steeping 2 grams of the dried aerial parts of passion flower in 250 mL of boiling water for 10 minutes has been used nightly for 7 nights (17374). There is insufficient reliable information available about the safety of passion flower when used topically.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. A specific passion flower product (Pasipay, Iran Darouk Pharmaceutical Company) has been used safely in children aged 6-13 years at a dose of 0.04 mg/ kg daily for 8 weeks (88197).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Some case reports suggest that passion flower use during the first and second trimesters of pregnancy may be associated with an increased risk for premature rupture of membranes and meconium aspiration syndrome; however, causality has not been confirmed (97279). The alkaloids harman and harmaline, which are sometimes found in passion flower, have been reported to have uterine stimulant activity (4,11020,95037). It is not known whether these constituents are present in sufficient quantities to have an effect.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about PASSION FLOWER)

There is insufficient reliable information available about the safety of skullcap.

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

(Read more about SKULLCAP)

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)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking motherwort concomitantly with other CNS depressants may increase the risk of sedation.  Details Motherwort has been reported to cause CNS depression and sedation (19,94205).

(Read more about MOTHERWORT)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, oats may have additive effects with antidiabetic agents and might increase the risk of hypoglycemia.  Details Consuming oats can decrease blood glucose in patients with diabetes (4980,4982,6266,103345). In those who require insulin, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control (103336).

INSULIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Concomitant use of oats and insulin might increase the risk of hypoglycemia.  Details In patients with insulin-dependent type 2 diabetes, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control (103336).

(Read more about OATS)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Concomitant use of passion flower with sedative drugs might cause additive effects and side effects.  Details Research in animals and humans shows that passion flower has sedative effects which can be additive when used with sedative medications like lorazepam (8007,19235,19236,19429,68309,104206).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, passion flower might decrease the effects of CYP3A4 substrates.  Details In vitro research suggests that passion flower can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer (110704).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, passion flower might reduce the bioavailability of OATP2B1 and OATP1A2 substrates.  Details In vitro research shows that the passion flower constituents apigenin and vitexin inhibit OATP2B1 and OATP1A2. This inhibition may be dose-dependent. One specific high-flavonoid passion flower extract (Valverde) seems to inhibit OATP2B1 and OATP1A2, while another extract with a lower flavonoid concentration (Arkocaps) shows less potent inhibition (105095). OATPs are responsible for the uptake of drugs and other compounds into the body; however, the specific activities of OATP2B1 and OATP1A2 are not well characterized.

(Read more about PASSION FLOWER)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, skullcap can have additive effects when used with other CNS depressants.  Details Animal and clinical research suggests that skullcap can cause sedation and cognitive impairment (12216,74008).

(Read more about SKULLCAP)

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 ...Orally or via intramuscular or intrauterine injection, motherwort appears to be generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, stomach irritation.
Topically: Contact dermatitis, photosensitivity.
Intramuscular / Intrauterine: Abdominal pain, erythema, eyelid edema, fever, nausea, pruritus, rash.

Dermatologic ...Motherwort leaves can cause contact dermatitis, and the oil may cause photosensitivity reactions (4). Intramuscularly and via intrauterine injection, mild erythema, rash, and pruritus have been reported (101892,104855).

Gastrointestinal ...Orally, use of motherwort in amounts greater than 3 grams can cause diarrhea and stomach irritation (12). Intramuscularly and via intrauterine injection, abdominal pain and nausea have been reported (104855).

Genitourinary ...Orally, use of motherwort in amounts greater than 3 grams can cause uterine bleeding (12).

Immunologic ...Motherwort can also cause allergic reactions in sensitive individuals (4). Intramuscularly and via intrauterine injection, transient fever and chills lasting less than 24 hours have been reported (104855).

Ocular/Otic ...Intramuscularly and via intrauterine injection, transient eyelid edema lasting less than 24 hours has been reported (104855).

(Read more about MOTHERWORT)

General ...Orally, oats are well tolerated.
Most Common Adverse Effects:
Orally: Abdominal distension, bloating, flatulence, and unpleasant taste.
Topically: Burning, contact dermatitis, itching, and redness.

Dermatologic ...Topically, oat-containing preparations can cause contact dermatitis (12515). Redness, burning, and itchiness have also been reported (103340).

Gastrointestinal ...When consumed orally, oats provide fiber. Increasing fiber in the diet can cause flatulence, bloating, abdominal distention, and unpleasant taste. To minimize side effects, doses should be slowly titrated to the desired level. These adverse effects usually subside with continued use (12514).
In patients who have difficulty chewing food, or those with conditions that decrease small bowel motility, oat bran may cause bezoars (concretions) and intestinal obstruction. Oats and oat bran are unlikely to cause obstruction without other causative factors (4979,4985).

(Read more about OATS)

General ...Orally, passion flower is well tolerated.
Most Common Adverse Effects:
Orally: Confusion, dizziness, hypersensitivity, and sedation.

Cardiovascular ...There is a case report involving a 34-year-old female who was hospitalized with severe nausea, vomiting, drowsiness, prolonged QT interval, and episodes of nonsustained ventricular tachycardia following use of passion flower extract tablets (Sedacalm, Bioplus Healthcare), 1500 mg on day 1 and 2000 mg on day 2 to relieve stress. All symptoms resolved within one week after passion flower was discontinued (6251).

Genitourinary ...The alkaloids harman and harmaline, which are sometimes found in small amounts in passion flower, have been reported to have uterine stimulant activity (4,11020,95037).

Hematologic ...Orally, passion flower has been reported to cause epistaxis in one clinical trial (95038). Vasculitis has also been reported with use of a specific herbal product (Relaxir) produced mainly from the fruits of passion flower (6).

Hepatic ...There is debate about whether passion flower contains cyanogenic glycosides. Several related Passiflora species do contain these constituents (3), including Passiflora edulis, which is associated with liver and pancreatic toxicity (7).

Immunologic ...An idiosyncratic hypersensitivity reaction characterized by urticaria and cutaneous vasculitis has been reported in a 77-year-old male with rheumatoid arthritis after taking a specific combination product that included passion flower extract (Naturest) (68308). It is unclear if these effects were caused by passion flower or other ingredients.
In clinical trials, passion flower has been reported to cause allergy symptoms including sinus irritation; however, the frequency of these events was statistically nonsignificant when compared to treatment with midazolam 15 mg (95038).

Musculoskeletal ...Orally, passion flower has been reported to cause muscle relaxation in a clinical trial (95038).

Neurologic/CNS ...Orally, sedation, dizziness, ataxia, and confusion have been reported in clinical trials. However, these events generally do not necessitate discontinuation (8007,15391,15392,95036,95038). Altered consciousness has been reported with use of a specific herbal product (Relaxir) produced mainly from the fruits of passion flower (6).

(Read more about PASSION FLOWER)

General ...There is currently a limited amount of information available on the adverse effects of skullcap.
Most Common Adverse Effects:
Orally: Cognitive impairment, digestive disturbances, sedation.

Gastrointestinal ...Orally, mild digestive disturbances were reported in around 9% of patients taking skullcap 350 mg three times daily for 2 weeks (91690).

Hepatic ...There are four reports of hepatotoxicity associated with products thought to contain skullcap. However, it is uncertain whether the products actually contained skullcap. It is thought that the products might have been contaminated with an adulterant such as germander (515), which is known to cause liver damage.

Neurologic/CNS ...A single skullcap extract dose of 100 mg does not seem to have adverse CNS effects. However, a higher dose of 200 mg might cause sedation and cognitive impairment (12216). One patient taking skullcap 350 mg three times daily for 2 weeks reported vivid dreams (91690). It is unclear if this event was associated with skullcap.

(Read more about SKULLCAP)