Melissa Supreme for Children [Discontinued] by Gaia Herbs

POSSIBLY EFFECTIVE

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

POSSIBLY INEFFECTIVE

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

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

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POSSIBLY EFFECTIVE

• Depression. Small clinical trials show that oral lemon balm may improve depression when used short-term; the long-term effects are unclear. It is also unclear if lemon balm aromatherapy is beneficial for depression. Details: A meta-analysis of randomized controlled trials in adults with depression and/or anxiety shows that using lemon balm, usually orally, daily for 3-56 days moderately improves depression scores when compared with control. Lemon balm was used orally as 1200-3000 mg daily or as aromatherapy for 30 minutes daily (110136). Other individual studies also show that oral lemon balm may modestly improve depression. A small clinical study in adults with mostly mild depression shows that taking lemon balm 2 grams daily for 8 weeks moderately improves depressive symptoms when compared with baseline. The improvement appears to be similar to taking lavender powder 2 grams daily or fluoxetine 20 mg daily (104433). However, this study was inadequately powered to detect differences between groups. A small clinical study in adults with type 2 diabetes and mild to moderate depression conducted in Iran shows that taking lemon balm extract capsules 350 mg twice daily for 12 weeks modestly reduces the severity of depression and anxiety based on validated patient-reported questionnaires when compared with placebo (111741). However, the interpretation of these findings is limited by methodological flaws in outcome analysis. Although studies have assessed oral lemon balm as monotherapy, its use in combination with other ingredients has also been explored. A small clinical study in patients with mild or moderate depression shows that taking lemon balm 600 mg with fertilized egg powder (Young Tissue Extract) 1,680 mg daily for 12 weeks improves symptoms when compared with placebo, but not when compared with taking fertilized egg powder alone (19534). Additionally, a single-center clinical study in Iranian adults with constipation-predominate irritable bowel syndrome (IBS-C) shows that taking a lemon balm, anise, and rose hip extract supplement twice daily for 4 weeks reduces anxiety and depression scores,on a patient-reported survey, when compared with placebo (115636). The validity of these results is limited by the lack of data regarding history or diagnosis of anxiety or depression. It is not clear if this effect is due to lemon balm, the other ingredients, or the combination.
• Herpes labialis (cold sores). Topical lemon balm 1% lotion seems to be beneficial for the healing of recurrent cold sores. Details: Clinical research in patients with recurring cold sores shows that applying a cream containing 1% lemon balm dried leaf extract (LomaHerpan, Infectopharm) at the early stages seems to shorten healing time and reduce symptoms of recurring cold sores when compared with placebo (790,9995).
• Stress. Oral lemon balm seems to be beneficial for improving experimentally-induced stress in some patients. Details: A small study in healthy adults suggests that a single dose of lemon balm extract 600 mg increases calmness and alertness during laboratory-induced psychological stress when compared with placebo (19524). Another small study in healthy adults shows that a single dose of lemon balm extract (Bluenesse, Vital Solutions) 300 mg added to food or drink reduces anxiety and improves memory and alertness during multi-task cognitive testing when compared with placebo (91733). Lemon balm has also shown benefit when used in combination with other ingredients for stress. Lemon balm 240 mg has been used in combination with valerian 360 mg (Songha Night, Pharmaton Natural Health Products) (19405). Lemon balm 50 mg has been used in combination with valerian root 90 mg, passion flower 90 mg, and butterbur 90 mg (Relaxane, Max Zeller Sӧhne AG) (97276).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral lemon balm is beneficial for improving cognitive function. Details: Preliminary clinical research in adults with age-related cognitive impairment shows that taking lemon balm leaf extract, standardized to contain 500 mg rosmarinic acid, orally daily for 96 weeks does not improve cognitive function scores when compared with placebo (110142).
• Alzheimer disease. It is unclear if oral lemon balm is beneficial for improving cognitive function. Details: A small clinical study in elderly patients with mild to moderate Alzheimer disease shows that taking a leaf extract of lemon balm (standardized to citral 500 mcg/mL) 60 drops daily for 4 months seems to reduce agitation and improve cognitive function when compared with placebo (9993). This study was limited by a large number of drop-outs in the placebo group. An even smaller clinical study in patients with mild Alzheimer disease shows that taking lemon balm extract containing 500 mg rosmarinic acid daily for 24 weeks does not seem to improve cognition, but might modestly improve neuropsychiatric symptoms, when compared with placebo (104435). The validity of these findings is limited because the study was not powered to evaluate cognition and neuropsychiatric symptoms.
• Anxiety. It is unclear if oral lemon balm or lemon balm aromatherapy is beneficial for reducing anxiety in most patients. Details: A meta-analysis of randomized controlled trials in adults with depression and/or anxiety shows that using lemon balm daily for 3-56 days moderately improves anxiety scores when compared with control. Lemon balm was used orally as 1200-3000 mg daily or as aromatherapy for 30 minutes daily (110136). The validity of this result is limited by high heterogeneity. Also, a small clinical study in patients with mild or moderate anxiety disorders shows that taking a specific standardized lemon balm extract (Cyracos, Naturex SA) 300 mg twice daily reduces anxiety-associated symptoms and improves sleep when compared with baseline (104425). The validity of this finding is limited by the lack of a comparator group. Another small clinical study in adults with type 2 diabetes and mild to moderate depression conducted in Iran shows that taking lemon balm extract capsules 350 mg twice daily for 12 weeks modestly reduces the severity of depression and anxiety based on validated patient-reported questionnaires when compared with placebo (111741). Although studies have assessed oral lemon balm as monotherapy, its use in combination with other ingredients has also been explored. A single-center clinical study in Iranian adults with constipation-predominate irritable bowel syndrome (IBS-C) shows that taking a lemon balm, anise, and rose hip extract supplement twice daily for 4 weeks reduces anxiety and depression scores, on a patient-reported survey, when compared with placebo (115636). The validity of these results is limited by the lack of data regarding history or diagnosis of anxiety or depression. It is not clear if this effect is due to lemon balm, the other ingredients, or the combination.
• Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral lemon balm for ADHD, there is insufficient reliable information about the clinical effects of lemon balm for this condition.
• Chronic bronchitis. Although there is interest in using oral lemon balm for bronchitis, there is insufficient reliable information about the clinical effects of lemon balm for this condition.
• Cognitive function. It is unclear if oral lemon balm is beneficial for improving memory and response time in healthy patients. Details: A small study in healthy young adults shows that taking a single dose of lemon balm 1600 mg increases memory accuracy, but may slow performance on timed memory tasks, when compared with placebo (19530). Another small study shows that taking a combination product containing equal parts lemon balm, sage, and rosemary, 5 grams of plant material per 10 mL solution, twice daily for 2 weeks might modestly improve delayed, but not immediate, word recall when compared with placebo in healthy adults 62 years of age or younger. No benefits were seen in adults 63 years of age and older (97277). It is not clear if this effect is due to lemon balm, the other ingredients, or the combination.
• Colic. Oral lemon balm has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical studies in breast-fed or formula-fed infants with colic show that giving specific multi-ingredient products containing lemon balm 65-97 mg and German chamomile 9-178 mg, with or without fennel 164 mg and inactivated Lactobacillus acidophilus (ColiMil; ColiMil Plus, Milte Italia SPA), orally twice daily for 1-4 weeks reduces crying times when compared with either placebo or simethicone (16735,96278). Another small clinical study in infants shows that giving 150 mL of a specific herbal tea preparation (Calma-Bebi, Bonomelli), containing German chamomile, vervain, licorice, fennel, and lemon balm, up to three times daily after an episode of colic for one week, modestly reduces colic when compared with placebo water without herbs (19715). It is not known if the benefits of these multi-ingredient preparations are due to lemon balm, other ingredients, or the combination.
• Delirium. Oral lemon balm has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults in the intensive care unit with agitation and delirium who are receiving quetiapine 50-200 mg every 12 hours shows that taking 5 mL of a syrup containing lemon balm leaf extract 50 mg and valerian root 625 mg orally every 12 hours improves agitation when compared to baseline. Although the improvement appeared to similar to that seen in those taking placebo, no statistical comparison was conducted between groups (106627).
• Dementia. It is unclear if oral lemon balm is beneficial for reducing neuropsychiatric symptoms of dementia, such as agitation. Details: A small clinical study in patients with severe dementia and agitation shows that applying a lotion containing essential oil of lemon balm to the faces and hands of patients for 4 weeks reduces agitation based on the Cohen-Mansfield Agitation Inventory (CMAI) scale when compared with applying a placebo lotion (19523). However, another small clinical study in patients with Alzheimer disease and prolonged agitation shows that applying lemon balm oil by gentle massage for 1-2 minutes twice daily for 12 weeks does not reduce agitation when compared with applying placebo oil (19522). The validity of these results is limited by the notable improvement observed in the placebo group, which may have been due to the regular physical touch and increased social interaction that occurred in this group. A small clinical study in patients with dementia shows that inhaling lemon balm oil from a small pad attached to the collar of clothing for 2 hours once daily for 2 weeks does not reduce agitation based on the Neuropsychiatric Inventory (NPI) and CMAI scales when compared with placebo (99710).
• Dyslipidemia. It is unclear if oral lemon balm is beneficial in patients with dyslipidemia. Details: A meta-analysis of 5 small clinical studies in adults shows that oral lemon balm extract, leaf powder, or tea in doses ranging from 700-4000 mg daily for 8-24 weeks reduces low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG) when compared with placebo; however, the clinical significance of these findings is unclear (115638). The validity of these results is limited by the heterogenous methods between clinical trials, including population, dose, and study duration.
• Dysmenorrhea. Although there is interest in using oral lemon balm for dysmenorrhea, there is insufficient reliable information about the clinical effects of lemon balm for this condition.
• Dyspepsia. Oral lemon balm has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of four small clinical studies in patients with IBS shows that using a specific combination product containing lemon balm (Iberogast, Steigerwald Arzneimittelwerk GmbH) 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. The combination includes lemon balm, peppermint leaf, German chamomile, caraway, licorice, clown's mustard plant, celandine, angelica, and milk thistle (13089). In another clinical study, taking a similar combination product containing extracts from peppermint leaf, clown's mustard plant, German chamomile flower, caraway, licorice root, and lemon balm (STW 5-II, Steigerwald Arzneimittelwerk GmbH), 1 mL orally three times daily for up to 8 weeks eliminates gastrointestinal symptoms in 40% more dyspepsia patients when compared with placebo (12724).
• Headache. Although there is interest in using oral lemon balm for headache, there is insufficient reliable information about the clinical effects of lemon balm for this condition.
• Hypertension. It is unclear if oral lemon balm is beneficial for hypertension. Details: Preliminary clinical research in adults with uncontrolled hypertension while on 1-3 active treatments shows that taking lemon balm extract 400 mg, standardized to contain 8 mg rosmarinic acid, orally daily for 4 weeks reduces systolic and diastolic blood pressure by 8% to 14% and 11% to 16%, respectively, when compared with baseline. These improvements were significant when compared with placebo (110138).
• Hyperthyroidism. Although there is interest in using oral lemon balm for hyperthyroidism, there is insufficient reliable information about the clinical effects of lemon balm for this condition.
• Insect repellent. Although there is interest in using topical lemon balm as insect repellant, there is insufficient reliable information about the clinical effects of lemon balm for this condition.
• Insomnia. It is unclear if oral lemon balm is beneficial for insomnia. Details: A small, cross-over clinical study in Italy in adults with self-reported poor sleep quality shows that taking a specific lemon balm phytosome (Meloff, Pharmextracta SpA) 400 mg 30 minutes prior to bed for 2 weeks improves some, but not all, measures of sleep quality when compared with placebo . (115637). However, it is unclear if these improvements are clinically significant. Additionally, lemon balm has been evaluated in combination with other ingredients. Taking a specific combination product providing lemon balm leaf extract 80 mg and valerian root extract 160 mg (Euvegal forte, Dr. Willmar Schwabe Pharmaceuticals) 2-3 times daily appears to improve the quality and quantity of sleep in healthy people and those diagnosed with insomnia or sleeping disorders (10423,19528,19536). However, lower daily doses may not improve sleep (10421). Other clinical research in healthy adults with insomnia shows that using a combination product containing ground lemon balm herb 1000 mg and aqueous extract of Nepeta menthoides 400 mg at bedtime for 4 weeks improves sleep quality and sleep duration and reduces sleep disturbance, sleep latency, and daytime dysfunction when compared with placebo (97278). A clinical study in children 12 years and younger shows that a specific combination product containing lemon balm leaf extract 80 mg and valerian root extract 160 mg (Euvegal forte, Dr. Willmar Schwabe Pharmaceuticals) 1-2 tablets once or twice daily might decrease symptoms of restlessness and dyssomnia when compared to baseline (14416). It is unclear if these effects are due to lemon balm, other ingredients, or the combinations.
• Irritable bowel syndrome (IBS). Oral lemon balm has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with IBS shows that using 30 drops of a combination product providing lemon balm, spearmint, and coriander (Carmint, PurSina Pharmacy) three times daily after meals for 8 weeks reduces abdominal pain and discomfort when added to standard treatment with loperamide or psyllium, compared to standard treatment alone (19535). It is not known if the effect is due to lemon balm, the other ingredients, or the combination.
• Menopausal symptoms. Oral lemon balm has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in postmenopausal adults with sleep disturbances shows that taking lemon balm leaf 250 mg and fennel fruit 250 mg orally once daily for 8 weeks improves menopausal symptoms including vasomotor, psychomotor-social, physical, and sexual symptoms, by 24% to 38% when compared with baseline. These improvements were significant when compared with placebo (110137).
• Pain (acute). It is unclear if lemon balm aromatherapy is beneficial for reducing pain in patients with acute coronary syndrome. Details: A small clinical study in patients with acute coronary syndrome presenting to the emergency department shows that aromatherapy with lemon balm leaf and stem essential oil 1% for 10 minutes twice on the day of presentation modestly reduces chest pain scores when compared with placebo. However, pain was no longer different between groups within 15 minutes after the second aromatherapy session (110139).
• Postpartum complications. Oral lemon balm might reduce postpartum pain in some patients; however, it's not clear if it is beneficial for other postpartum complications. Details: A small clinical study shows that taking lemon balm leaf extract 395 mg every 6 hours for 24 hours following childbirth is slightly more effective for reducing postpartum pain when compared with taking mefenamic acid 250 mg using the same dosing schedule (101763).
• Psoriasis. Oral lemon balm has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with mild to moderate psoriasis shows that taking an oral combination product containing lemon balm, rose hip, and fennel as 10 mL three times daily for 12 weeks improves pruritus and psoriasis scores by 45% and 49%, respectively, when compared with baseline. In contrast, these scores worsened in the placebo group (110141). The validity of this finding is limited by the lack of statistical comparison between groups.
• Somatic symptom disorder. Oral lemon balm has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in individuals with somatic symptom disorder shows that taking one tablet of a combination product three times daily for 2 weeks seems to improve symptoms of depression and anxiety when compared with placebo. Each tablet of this product contains lemon balm leaf extract 60 mg, valerian root extract 90 mg, and passionflower herb extract 90 mg (19701). It is not known if the effect is due to lemon balm, other ingredients, or the combination.
• Ventricular arrhythmias. It is unclear if oral lemon balm leaf tea is beneficial for patients with premature ventricular contraction (PVC). Details: Preliminary clinical research in adults with low to moderate PVCs shows that drinking lemon balm leaf tea twice daily for 12 weeks reduces the frequency of PVCs by 32% when compared with baseline. This improvement was significant when compared with no treatment. Lemon balm tea also modestly improved heart rate, but not left ventricular ejection fraction, when compared with no treatment. The tea was prepared by steeping lemon balm leaf 2 grams in 250 mL of boiling water (110140). More evidence is needed to rate lemon balm for these uses.

(Read more about LEMON BALM)

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).
• Dyslipidemia. 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, especially 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 (4976,4977,5786,5788,5792,5794,5795,8521,107749,113488,113495). For example, eating 3 bowls of oatmeal (28 gram servings) daily, providing a total of 3 grams of soluble fiber daily, can decrease total cholesterol by about 5 mg/dL (5788). However, consuming more than 10 grams of soluble fiber daily doesn't seem to increase effectiveness (5788). A meta-analysis comparing the effects of oats and isolated beta-glucans shows that both products similarly impact lipid profiles, suggesting that the bioactive component of oats are beta-glucans (113488). 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). Although oats are shown to lower total and LDL cholesterol, a meta-analysis and a small clinical study in adults with and without dyslipidemia shows that consuming oatmeal or oat products does not reduce triglycerides or increase high-density lipoprotein (HDL) cholesterol when compared with controls (113488,113495).

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 moderately reduces 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: A meta-analysis of 21 clinical studies in healthy adults and those with a variety of metabolic conditions including hypertension shows that consumption of oat products reduces systolic blood pressure (SBP) by 3 mmHg but has no effect on diastolic blood pressure (DBP) when compared with control. Subgroup analysis suggests that consuming oat products reduces SBP by 10 mmHg in patients with hypertension at baseline. An additional subgroup analysis suggests that consuming at least 5 grams of beta-glucan-enriched oats daily or consuming oats for a duration at least 8 weeks reduces SBP and DBP (113494). Observational research has found that consumption of oats as oatmeal or oat cereal does not seem to reduce DBPor SBP in males with minor elevations in blood pressure or patients with dyslipidemia (2956,113495). 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.
• Insomnia. Moderate-sized clinical studies suggest that oral passion flower may modestly improve total sleep time in patients with insomnia; however, its effects on sleep latency and maintenance are mixed. Details: A moderate-sized clinical study in adults in India with insomnia and stress shows that taking passion flower extract 600 mg daily at bedtime for 30 days increases total sleep time by about 30 minutes and reduces both the time to fall asleep and wake time after sleep onset by about 10 minutes when compared with placebo (114529). The validity of these findings is limited by lack of reporting on baseline use of medications or other substances which may impact sleep and exclusion of patients with severe insomnia. Another moderate-sized clinical study 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). Additionally, a 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).
• 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.
• 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. It is unclear if oral passion flower reduces stress. Details: A moderate-sized clinical study in adults in India with stress and insomnia shows that taking passion flower 600 mg daily at bedtime for 30 days modestly reduces stress when compared with placebo (114529). It is unclear how changes in stressors over the course of the study may have affected results. Additionally, 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

• Fatigue. It is unclear if oral sea moss is beneficial for increasing energy. Details: A small observational study in a heterogenous population of patients with various subjective symptoms at baseline has evaluated the effects of overwintered and stressed sea moss versus non-overwintered or stressed sea moss. This study found that the overwintered and stressed sea moss powder, taken as 500 mg three times daily for 3 weeks, is associated with improvements in exhaustion and fatigue in about 36% of patients and improvements in strength and energy in 84% of patients. The non-overwintered or stressed sea moss powder, taken in the same dose, is associated with improvements of about 18% and 27%, respectively (109121). This study is limited by the subjective nature of the reported symptoms and the lack of an appropriate comparator group.
• Iodine deficiency. Although there is interest in using oral sea moss as a source of iodine, there is insufficient reliable information about the clinical effects of sea moss for this use.
• Muscle strength. Although there is interest in using oral sea moss for muscle support in athletes, there is insufficient reliable information about the clinical effects of sea moss for this use.
• Pain (chronic). It is unclear if oral sea moss is beneficial for pain reduction. Details: A small observational study in a heterogenous population of patients with various subjective symptoms at baseline has evaluated the effects of overwintered and stressed sea moss versus non-overwintered or stressed sea moss. This study found that the overwintered and stressed sea moss powder, taken as 500 mg three times daily for 3 weeks, is associated with a reduction in pain in 10% of patients, compared with 0% of patients taking non-overwintered or stressed sea moss powder (109121). This study is limited by the subjective nature of the reported symptoms and the lack of an appropriate comparator group.
• Quality of life. It is unclear if oral sea moss is beneficial for improving quality of life. Details: A small observational study in a heterogenous population of patients with various subjective symptoms at baseline has evaluated the effects of overwintered and stressed sea moss versus non-overwintered and stressed sea moss. This study found that the overwintered or stressed sea moss powder, as 500 mg three times daily for 3 weeks, is associated with an improvement in mood in 26% of patients, compared with only 3% of those taking non-overwintered or stressed sea moss powder (109121). This study is limited by the subjective nature of the reported symptoms and the lack of an appropriate comparator group. More evidence is needed to rate sea moss for these uses.

(Read more about SEA MOSS)

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

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

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about GOTU KOLA)

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

POSSIBLY SAFE ...when used orally and appropriately, short-term. Lemon balm extract has been used with apparent safety at a dose of 500 mg daily for 6 months or at a dose of 3000 mg daily for 2 months (9993,9994,104435,104435,110136). ...when used topically and appropriately, short-term. Lemon balm 1% dried leaf extract has been used up to 4 times daily with apparent safety for a few days (790,9995).

CHILDREN: POSSIBLY SAFE
when used orally and appropriate, short-term. A single dose of lemon balm extract 3-6 mg/kg has been safely used in children aged 6-7 years (19525). A specific combination product providing lemon balm leaf extract 80 mg and valerian root extract 160 mg (Euvegal forte, Dr. Willmar Schwabe Pharmaceuticals) 1-2 tablets once or twice daily has been safely used in children under 12 years of age for 30 days (14416). In infants up to 4 weeks old, multi-ingredient products (ColiMil, ColiMil Plus) containing lemon balm 64-97 mg daily have been used with apparent safety for up to 7 days (16735,96278).

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

(Read more about LEMON BALM)

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.

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LIKELY SAFE ...when sea moss is used orally in the amounts found in foods (109120). There is insufficient reliable information available about the safety of sea moss when used in medicinal amounts. However, sea moss contains iodine in a concentration of approximately 4-7 mcg per gram. Total daily intake of iodine above the tolerable upper intake level (UL) of 1100 mcg should be avoided (109117).

PREGNANCY AND LACTATION: LIKELY SAFE
when used in food amounts (109120). There is insufficient reliable information available about the safety of using larger amounts; avoid using.

(Read more about SEA MOSS)

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

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

(Read more about SKULLCAP)

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

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

(Read more about GOTU KOLA)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of lemon balm might have additive effects with CNS depressant drugs.  Details Lemon balm seems to have CNS depressant activity in animals and in humans (9994,19725).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, lemon balm might interfere with thyroid hormone replacement therapy.  Details In vitro, constituents of lemon balm extract bind to thyroid stimulating hormone (TSH), preventing TSH receptor-binding and leading to the inhibition of TSH-stimulated adenylate cyclase activity (19727,19728). In animals, lemon balm extract has been shown to decrease levels of circulating TSH and inhibit thyroid secretion (19726).

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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).

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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.

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AMIODARONE (Cordarone) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining sea moss with amiodarone might cause excessively high iodine levels.  Details Amiodarone contains 37.3% iodine and can increase iodine levels. Concomitant use with sea moss, which contains approximately 4-7 mcg of iodine per gram, might increase the risk of adverse effects from iodine, including altered thyroid function (109117).

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, sea moss might alter the effects of antithyroid drugs.  Details Sea moss contains approximately 4-7 mcg of iodine per gram (109117). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking sea moss could theoretically alter the effects of antithyroid drugs.

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, sea moss might alter the effects of thyroid hormone.  Details Sea moss contains approximately 4-7 mcg of iodine per gram (109117). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking sea moss could theoretically alter the effects of thyroid hormone.

(Read more about SEA MOSS)

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

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

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

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

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

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

(Read more about GOTU KOLA)

General ...Orally, lemon balm seems to be well tolerated in food amounts and larger, medicinal amounts. Topically, lemon balm seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Wheezing has been rarely reported.

Cardiovascular ...Orally, a case of transient complete atrioventricular block and QT prolongation is reported in a 25-year-old female following the post-workout use of a specific product (Muscle Eze Advanced) containing lemon balm and several other ingredients. Symptoms of fatigue and lightheadedness started 1 week into use of the product. Product discontinuation led to restoration of normal sinus rhythm within 24 hours and normalization of the electrocardiogram within 2 weeks (112556). It is unclear whether this occurrence is due to lemon balm, other ingredients, or the combination.

Dermatologic ...Topically, lemon balm 1% cream applied 5 times daily to cold sores has been associated with two cases of irritation and one case of cold sore exacerbation. However, these effects do not appear to occur more often with lemon balm than with placebo (790).

Gastrointestinal ...Orally, lemon balm might increase appetite in some patients (91732,104433). Nausea, vomiting, and abdominal pain have been reported rarely and do not seem to occur more often than in patients taking placebo (9993).

Neurologic/CNS ...Orally, lemon balm has been reported to cause dizziness and sedation; however, it does not seem to occur more often with lemon balm than placebo (9993,104433). Additionally, other clinical research shows that using lemon balm in conjunction with alcohol does not affect reaction time or influence cognitive performance (19427,19723).

Pulmonary/Respiratory ...Orally, lemon balm has been associated with rare cases of wheezing (9993).

(Read more about LEMON BALM)

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).

Immunologic ...In a case report, a 45-year-old male developed acute generalized urticaria, facial angioedema, and dyspnea immediately after consuming oat flour. The reaction resolved after emergency care for anaphylaxis. Further investigation revealed an IgE-mediated hypersensitivity reaction to oat proteins (113490).

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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 ...Orally, sea moss is well tolerated when used appropriately.

Gastrointestinal ...Orally, see moss has been reported to cause constipation and diarrhea in one observational study (109121).

(Read more about SEA MOSS)

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)