Clarycalm by 4 Today

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Obesity. Preliminary clinical research suggests a specific combination product, containing 1,3-DMAA, caffeine, and other ingredients (OxyELITE Pro, USPLabs), could potentially affect weight or body fat loss. Taking a single 2-capsule dose seems to significantly increase calorie expenditure and markers of lipolysis within 1-2 hours compared to placebo in a small sample of healthy, exercise trained men and women (17906). However, in an 8-week trial, taking this supplement did not significantly reduce weight or increase fat loss compared to placebo (17907). In the single-dose trial, taking the supplement significantly increased blood pressure and heart rate, suggesting the potential for adverse cardiovascular effects (17906). However, in an 8-week study, heart rate was significantly increased, but not blood pressure (17907). More evidence is needed to rate 1,3-DMAA for this use.

(Read more about 1,3-DMAA)

POSSIBLY EFFECTIVE

• Hyperlipidemia. Oral bergamot seems to reduce levels of low-density lipoprotein (LDL) cholesterol in patients with hyperlipidemia. It is unclear if bergamot is beneficial for improving high-density lipoprotein (HDL) cholesterol or triglyceride levels. Details: Preliminary clinical research in patients with hyperlipidemia shows taking a bergamot polyphenol fraction 1000 mg orally daily for 30 days increases HDL cholesterol and decreases total cholesterol, LDL cholesterol, and triglycerides similarly to rosuvastatin 10 mg daily, but to a lesser extent than rosuvastatin 20 mg daily. Taking the bergamot polyphenol fraction 1000 mg daily in combination with rosuvastatin 10 mg daily appears to result in similar improvements as those seen with rosuvastatin 20 mg daily (96357). A meta-analysis of 5 clinical trials shows that taking bergamot 500-1300 mg daily reduces total cholesterol, LDL cholesterol, and triglyceride levels, and increases HDL cholesterol levels. However, the included studies had high heterogeneity (109982). Clinical research in overweight or obese patients with mild hypercholesterolemia shows that taking bergamot phytosome (Vazguard, Indena SpA) 500 mg twice daily for 12 weeks modestly decreases total and LDL cholesterol, but does not affect HDL cholesterol or triglyceride levels, when compared with placebo (105317). Also, preliminary clinical research in statin-intolerant patients with moderate hypercholesterolemia shows that taking a specific bergamot extract (Bergavit, Bionap) providing 150 mg flavonoids daily for 6 months reduces LDL cholesterol and triglycerides by 20% and 17%, respectively, and increases HDL cholesterol by 8%, when compared with baseline (102599). Bergamot has also been evaluated in combination with other ingredients, usually in lower doses than the studies with single-ingredient products, and with inconsistent results (109982). One product (Colber, Esserre Pharma srl), containing bergamot extract, phytosterols, vitamin C, and dry artichoke extract, was taken as 2 pills daily for 8 weeks (102596); another product (CitriCholess, GardaVita Inc.), containing bergamot extract 500 mg along with unspecified additional ingredients, was taken daily for 12 weeks (96366). Another specific product (Vazguard; Indena SpA), containing bergamot phytosome 600 mg and artichoke leaf extract (Indena SpA) 100 mg, has also shown benefit in patients with mild hypercholesterolemia when taken twice daily for 2 months (108712). However, it is unclear if any effects from these products are due to bergamot, other ingredients, or the combination.

POSSIBLY INEFFECTIVE

• Anxiety. Inhaled bergamot essential oil does not seem to be beneficial for anxiety associated with radiotherapy treatment. Details: Clinical research in patients receiving concurrent radiotherapy shows that using bergamot essential oil as aromatherapy does not reduce anxiety when compared with placebo (11452).
• Mental alertness. Inhaled bergamot essential oil does not seem to improve mental alertness. Details: Some clinical research shows that using bergamot essential oil as aromatherapy does not improve mental alertness and might actually impair mental alertness in healthy people due to its relaxing effects (34438,34440).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Antipsychotic-induced metabolic side effects. It is unclear if oral bergamot is beneficial for reducing antipsychotic-induced metabolic side effects. Details: Preliminary clinical research shows that taking bergamot extract (Bergamot Polyphenolic Fraction BPF, H&AD SRL) 500 mg orally daily for 60 days along with dietary advice does not affect body weight, body mass index, glucose, or lipid parameters when compared to baseline in patients taking second generation antipsychotics (96355). The lack of a comparator group limits the validity of these results.
• Aromatase inhibitor-induced arthralgia. Oral bergamot has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in postmenopausal adults with aromatase inhibitor-induced arthralgia shows that taking two tablets of a product containing bergamot juice flavonoids, phytosterols, artichoke leaf extract, and vitamin C (ColBer, Esserre Pharma SRL) orally daily for 6 months along with dieting and exercise modestly reduces joint pain when compared to baseline (96367). The lack of a comparator group limits the validity of these results.
• Autism spectrum disorder. It is unclear if inhaled bergamot essential oil is beneficial for reducing anxiety in children with autism spectrum disorder. Details: Preliminary clinical research in children aged 6-11 years with autism spectrum disorder shows that inhaling 5 drops of bergamot essential oil on a scent strip for 15 minutes while waiting in a medical office does not reduce anxiety when compared with no aromatherapy (102597).
• Depression. Inhaled bergamot essential oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in community-dwelling older adults shows that a combination of lavender, sweet orange, and bergamot essential oils in a 2:1:1 ratio, for a final combined concentration of 1% in sweet almond oil, administered via inhalation or aromatherapy massage to the upper body with 5 mL of the combination oil, twice weekly for 8 weeks improves symptoms of depression in 55% to 65% of patients when compared with control (98474). It is unclear if this benefit is associated with bergamot, other aromatherapy oils, or the combination.
• Impaired glucose tolerance (prediabetes). Oral bergamot has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with prediabetes shows that taking a product containing fenugreek seed extract 200 mg, olive leaf extract 100 mg, and bergamot extract 500 mg for 6 months does not improve levels of glycated hemoglobin (HbA1c), fasting glucose or insulin, insulin resistance, or lipids, when compared with placebo (102251).
• Insomnia. Inhaled bergamot essential oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients hospitalized for cardiac rehabilitation shows that bedside aromatherapy with lavender, ylang ylang, and bergamot in a 1:1:1 ratio on a cotton ball for 5 nights moderately improves subjective sleep quality, but not sleep duration or sleep time, when compared with placebo (102594).
• Lice. Although there is interest in using topical bergamot oil for lice, there is insufficient reliable information about the clinical effects of bergamot for this purpose.
• Menopausal symptoms. Inhaled bergamot oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in postmenopausal adults with mild to moderate anxiety shows that inhaling bergamot oil 0.04% with lavender oil 5% as aromatherapy three times daily for 8 weeks reduces anxiety and depression symptom scores when compared with placebo (109981).
• Metabolic syndrome. Oral bergamot has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with both nonalcoholic fatty liver disease and metabolic syndrome, preliminary clinical research shows that taking a combination of a bergamot polyphenolic fraction 650 mg, oleuropein 20% 100 mg, and ascorbic acid 50 mg twice daily for 120 days modestly reduces levels of fasting blood glucose, low-density lipoprotein (LDL) cholesterol, and triglycerides and increases high-density lipoprotein (HDL) cholesterol levels when compared with baseline (105318). The validity of these findings is limited by the lack of a comparator group.
• Mycosis fungoides. Although there is interest in using topical bergamot oil for mycosis fungoides, there is insufficient reliable information about the clinical effects of bergamot for this condition.
• Nausea and vomiting. It is unclear if inhaled bergamot essential oil is beneficial for nausea and vomiting in children undergoing stem cell transplantation. Details: Preliminary clinical research shows that using bergamot essential oil (Elizabeth Van Buren) as aromatherapy does not reduce nausea when compared with an unscented control in children and adolescents undergoing stem cell transplantation (90508).
• Nonalcoholic fatty liver disease (NAFLD). Oral bergamot has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with both NAFLD and metabolic syndrome, preliminary clinical research shows that taking a combination of a bergamot polyphenolic fraction 650 mg, oleuropein 20% 100 mg, and ascorbic acid 50 mg twice daily for 120 days modestly reduces levels of fasting blood glucose, low-density lipoprotein (LDL) cholesterol, and triglycerides and increases high-density lipoprotein (HDL) cholesterol levels when compared to baseline. It also improves ultrasonographic markers of NAFLD (105318). The validity of these findings is limited by the lack of a comparator group. Bergamot polyphenolic fraction has also shown some benefit in combination with artichoke extract. In patients with NAFLD and type 2 diabetes, preliminary clinical research shows that taking a specific product (Bergacyn, Seris srl) containing 150 mg each of these ingredients, daily for 16 weeks, modestly improves levels of liver markers when compared with placebo; although bergamot polyphenolic fraction alone may have modest benefits, comparisons to the placebo group were lacking (105315). In patients with NAFLD without diabetes, clinical research shows that taking a similar combination for 12 weeks reduces liver fat by approximately 80% more than placebo. After controlling for a modest weight reduction in patients using this product, this benefit was limited to individuals over 50 years of age (105316).
• Obesity. It is unclear if oral bergamot is beneficial for weight loss or improving metabolic parameters in adults with obesity. Details: Clinical research in overweight or obese patients with mild hypercholesterolemia shows that taking bergamot phytosome (Vazguard, Indena SpA) 500 mg twice daily for 12 weeks modestly decreases visceral adipose tissue and levels of total and low-density lipoprotein cholesterol when compared with placebo. However, there was no effect on body weight, fat mass, high-density lipoprotein cholesterol, triglycerides, or glycemic indices (105317). A clinical study in adults with obesity following a reduced-calorie diet and performing 30-60 minutes of daily, light-intensity exercise, shows that a specific oral product (CitruSlim; NHR Science) containing bergamot extract 83% and Eurycoma longifolia root extract 17%, taken as 200 mg or 400 mg daily as three divided doses before meals for 112 days, decreases body mass index by 3.3% and 3.2%, respectively, but does not impact lipid parameters or waist-to-hip ratio, when compared with diet and exercise alone (108452). It is unclear if this effect is due to bergamot, Eurycoma longifolia, or the combination.
• Postpartum depression. It is unclear if inhaled bergamot essential oil is beneficial for reducing depressive symptoms in postpartum adults. Details: A small clinical trial in healthy adults voluntarily residing in a postpartum care center in Taiwan for 1 month shows that diffusing bergamot essential oil as aromatherapy daily for 15 minutes, beginning after childbirth and continuing for approximately 3 weeks, modestly reduces scores on the Edinburgh Postnatal Depression Scale, but not on the Postpartum Sleep Quality Scale, when compared with diffusing water. However, these patients did not have a diagnosis of postpartum depression at baseline, and depression scores improved in both groups (108992). The validity of these findings is limited by concerns with the study methodology.
• Psoriasis. It is unclear if topical bergamot is beneficial for chronic plaque psoriasis. Details: Preliminary clinical research shows that applying bergamot essential oil topically 30 minutes prior to ultraviolet B (UVB) therapy three times weekly is no more effective than UVB therapy alone for reducing plaque severity in patients with chronic plaque psoriasis. The duration of treatment varied according to plaque outcome, with discontinuation occurring either after plaque resolution, or after five consecutive procedures produced no observable effects (34381).
• Pre-procedural anxiety. It is unclear if inhaled bergamot essential oil is beneficial for reducing preoperative anxiety in adults or children. Details: In patients undergoing laparoscopic cholecystectomy, preliminary clinical research shows that bergamot essential oil as aromatherapy has a small beneficial effect on anxiety when compared with inhalation of grape seed oil (105319). However, bergamot essential oil (Elizabeth Van Buren) as aromatherapy does not appear to help reduce anxiety in children and adolescents undergoing stem cell transplantation (90508).
• Schizophrenia. It is unclear if oral bergamot is beneficial for improving executive functioning in patients with schizophrenia. Details: Preliminary clinical research in patients with schizophrenia taking second generation antipsychotics shows that taking a bergamot extract product (Bergamot Polyphenolic Fraction BPF, H&AD SRL) 500 mg orally twice daily for 8 weeks improves some, but not all, measures of executive functioning when compared to baseline (96356). The validity of these findings is limited by the lack of a comparator group.
• Vitiligo. Although there is interest in using topical bergamot oil for vitiligo, there is insufficient reliable information about the clinical effects of bergamot for this condition. More evidence is needed to rate bergamot for these uses.

(Read more about BERGAMOT)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dysmenorrhea. Clinical research in young women with moderate to severe dysmenorrhea shows that use of an aromatic massage cream containing lavender, clary sage, and marjoram oils daily during a menstrual cycle modestly reduces pain. On the second and third days of the next cycle, pain was reduced by 45% to 60% compared with a reduction of 20% to 40% with a placebo cream containing a synthetic fragrance. However, the aromatic cream did not reduce pain on the first day of the cycle, when pain was most severe (58095). It is not clear if these effects are due to topical application, aromatherapy, clary sage, the other ingredients, or a combination of these factors.
• Postoperative nausea and vomiting (PONV). Preliminary clinical research in patients undergoing percutaneous nephrolithotomy shows that inhaling clary sage essential oil aromatherapy for 5 minutes immediately after the operation, and again 3 and 6 hours after, does not improve nausea or vomiting when compared with a control group not receiving aromatherapy (103872).
• Postoperative pain. Preliminary clinical research in patients undergoing percutaneous nephrolithotomy shows that inhaling clary sage essential oil aromatherapy for 5 minutes immediately after the operation, and again 3 and 6 hours after, does not reduce pain when compared with a control group not receiving aromatherapy (103872). More evidence is needed to rate the effectiveness of clary sage for these uses.

(Read more about CLARY SAGE)

There is insufficient reliable information available about the effectiveness of Eastern red cedar.

(Read more about EASTERN RED CEDAR)

POSSIBLY EFFECTIVE

• Dysmenorrhea. Taking fennel oil or extract by mouth may reduce pain in patients with primary dysmenorrhea. This benefit may be similar to ibuprofen or mefenamic acid. Details: Two separate meta-analyses in patients with primary dysmenorrhea show that taking fennel oil or fennel extract for 1-6 menstrual cycles reduces dysmenorrhea pain when compared with placebo. Improvement in pain was similar when compared with ibuprofen or mefenamic acid. In the included studies, doses of fennel oil ranged from 3-30 drops every 4-8 hours, and doses of fennel extract ranged from 30-230 mg daily (104196,108972). However, most studies included in these meta-analyses were small and low-quality, and all studies were conducted in Iran. Higher quality studies in other geographic locations are needed to confirm these findings.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there has been interest in using oral fennel for anxiety, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Bronchitis. Although there has been interest in using oral fennel for bronchitis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cancer. Although there has been interest in using oral fennel for cancer prevention, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cholera. Although there has been interest in using oral fennel for cholera, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Colic. Small clinical studies suggest that oral fennel may reduce crying time in infants with colic. However, most research to date has evaluated fennel in combination with other ingredients. Details: A meta-analysis of three small clinical studies shows that giving fennel to infants with colic can reduce crying time by about 72 minutes daily when compared with placebo (97497). However, the studies included in this meta-analysis were at medium to high risk of bias, and the placebo response rate was high in all of the included studies. Additionally, two of the three studies evaluated combination products (16735,19715,49428). In the one study that used fennel alone, administering 5-20 mL of fennel seed oil 0.1% emulsion daily for one week led to colic relief in 65% of infants, compared with 24% of infants receiving placebo (49428). The other studies evaluated fennel in combination with lemon balm and German chamomile (ColiMil) or in combination with chamomile, vervain, licorice, and lemon balm (Calma-Bebi, Bonomelli). These combination products produced a response in 57% to 85% of infants, compared with 26% to 49% of infants receiving placebo (16735,19715).
• Constipation. Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small crossover trial in patients with constipation shows that drinking an herbal tea containing 3 grams of a combination of fennel, anise, elderberry, and senna daily for 5 days can decrease colonic transit time, increase the number of daily evacuations, and improve the perception of bowel function when compared with placebo (49494). Another small clinical study in elderly patients with constipation shows that drinking a specific tea (Smooth Move, Traditional Medicinals) containing fennel, senna, licorice, orange peel, cassia cinnamon, coriander, and ginger for 28 days can increase the number of bowel movements when compared to baseline (46196). The validity of this finding is limited by the lack of a comparator group. Additionally, a small clinical study in patients aged 60-65 years with functional constipation shows that taking a traditional Iranian combination product containing 5 grams each of fennel seed and rose flower, dissolved in water twice daily before meals for 4 weeks, improves constipation severity and stool consistency when compared with polyethylene glycol 10 grams. Improvements in constipation severity persisted in both groups 4 weeks after treatment completion (108973). However, polyethylene glycol is usually taken at a higher dose of 17 grams daily, limiting the validity of these findings.
• Cough. Although there has been interest in using oral fennel for cough, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dementia. Although there has been interest in using oral fennel for dementia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Diabetes. Although there has been interest in using oral fennel for diabetes, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dyspepsia. Although there has been interest in using oral fennel for dyspepsia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Flatulence. Although there has been interest in using oral fennel for flatulence, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Hirsutism. It is unclear if topical fennel is beneficial in patients with hirsutism. Details: A small clinical study in females with male pattern body hair due to unknown causes shows that applying a fennel 2% cream twice daily for 12 weeks can reduce hair diameter by approximately 19% when compared with placebo (49429).
• Insomnia. Although there has been interest in using oral fennel for insomnia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Irritable bowel syndrome (IBS). Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults with either diarrhea- or constipation-predominant IBS shows that taking two capsules containing fennel essential oil 25 mg and curcumin 42 mg per capsule (CU-FEO, Alfa Wassermann S.p.A.) twice daily for 30 days improves overall ratings of abdominal pain, abdominal distention, and quality of life by 24% when compared with placebo (97422).
• Lactation. Although there has been interest in using oral fennel to stimulate breastmilk production, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Menopausal symptoms. Small clinical studies suggest that oral fennel oil or fennel seed powder may modestly improve menopausal symptoms. Details: One small clinical trial in adults with medium severity menopausal symptoms shows that taking fennel essential oil 60 mg daily for 8 weeks improves scores on the Menopause Rating Scale when compared with a sunflower oil placebo (97498). Another small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks improves scores on the Kupperman Menopausal Index when compared with placebo (104198). Fennel has also been evaluated in combination with other ingredients. One small clinical study shows that taking a combination of fennel 120 mg, chamomile 1000 mg, and saffron 60 mg daily for 12 weeks reduces physical, psychological, and urogenital symptom scores on the Menopause Rating Scale when compared with placebo or lower doses of the combination (103628). Additionally, a moderate-sized clinical study in postmenopausal women conducted in Iran shows that taking combined fennel and valerian extract 500 mg twice daily for 8 weeks modestly improves self-reported scores for frequency and severity of hot flashes but does not improve sleep quality or duration of hot flashes when compared with placebo (112369). However, it is unclear if these benefits are due to fennel, other ingredients, or the combination.
• Nausea and vomiting. Although there has been interest in using oral fennel for nausea and vomiting, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Nocturnal enuresis. Although there has been interest in using oral fennel for nocturnal enuresis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Osteoarthritis. It is unclear if oral fennel extract is beneficial in patients with knee osteoarthritis. Details: A small clinical trial in females with osteoarthritis of the knee shows that taking powdered fennel extract 800 mg daily for 2 weeks reduces pain and disability scores, but not stiffness, when compared with placebo (104199).
• Polycystic ovary syndrome (PCOS). It is unclear if oral fennel is beneficial in patients with PCOS. Details: A small clinical study in patients with PCOS shows that taking two fennel capsules, containing anethole 21-27 mg per capsule, daily along with a hypocaloric standard diet or a hypocaloric high-protein diet for 3 months does not reduce body weight or improve androgenic parameters such as testosterone levels, sex hormone-binding globulin levels, or free androgen index, when compared with these diets plus placebo (104197). Fennel has also been evaluated in combination with other ingredients. A clinical study in patients with oligomenorrhea due to PCOS shows that taking a traditional combination product (Aslagh) containing equivalent amounts of essential oils of fennel, wild carrot seeds, and Vitex agnus-castus fruit for 3 months, either alone or in combination with metformin, improves rates of menstrual bleeding and menstrual cyclicity similarly to metformin alone. All three groups experienced a significant improvement from baseline. Aslagh was taken as two, 500-mg capsules twice daily, except during menses; metformin was titrated over one week to a dose of 500 mg three times daily (108974). Additionally, a moderate-sized clinical study in patients with PCOS shows that taking fennel 60 mg and Elwendia persica 25 mg twice daily for 4 months modestly improves number of ovarian follicles and body mass index when compared with placebo; however, when compared to baseline, the combination also improves hirsutism scores and menstrual cycle duration and interval (112370). It is unclear if these effects are due to fennel, other ingredients, or the combination.
• Rheumatoid arthritis (RA). Although there has been interest in using oral fennel for RA, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Sexual desire. It is unclear if oral fennel is beneficial for improving sexual desire. Details: A small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks does not improve scores on the Hurlbert Index of Sexual Desire when compared with placebo (104198).
• Sunburn. It is unclear if topical fennel emulsion is beneficial for preventing sunburn. Details: A small clinical study shows that applying a fennel 5% emulsion topically prior to ultraviolet (UV) exposure can reduce sunburn by 65% when compared with a control (49518).
• Upper respiratory tract infection (URTI). Although there has been interest in using oral fennel for upper respiratory tract infections, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Vaginal atrophy. It is unclear if intravaginal application of fennel cream is beneficial in patients with vaginal atrophy. Details: A small clinical study in postmenopausal adults shows that applying 5 grams of a fennel 5% cream to the vagina once daily for 8 weeks seems to reverse vaginal thinning, improve vaginal pH, and reduce symptoms of vaginal atrophy such as itching, dryness, and pain with intercourse when compared with placebo (92509). Patients in the fennel group also rated their sexual function to be improved when compared with those receiving placebo (97496). More evidence is needed to rate fennel for these uses.

(Read more about FENNEL)

POSSIBLY EFFECTIVE

• Acute Bronchitis. Oral Pelargonium sidoides may be beneficial in adults and children with acute bronchitis when initiated within 48 hours of symptom onset. Details: Several clinical studies and a meta-analysis of 6 small-to-moderate sized clinical studies in adults and children with acute bronchitis show that taking Pelargonium sidoides extract daily, starting within 48 hours of symptom onset, significantly reduces symptoms such as cough intensity and rales after 7 days of treatment when compared with placebo. Additionally, patients report an earlier onset of effect and increased remission of cough when compared with placebo (14258,16647,16649,16651,81557,81565,94580,110015,112124). Another meta-analysis of 6 clinical trials in children aged 6-10 years with acute bronchitis or acute tonsillopharyngitis shows that taking a specific Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 20 drops three times daily for 6 days reduces the amount of acetaminophen co-medication required to treat fever when compared with placebo (112126). However, most of the outcomes in these studies were patient-reported. Additionally, it is unclear whether any improvements are clinically significant. Various formulations of Pelargonium sidoides have been investigated. A specific liquid extract of Pelargonium sidoides containing the active ingredient EPs 7630 (Dr. Willmar Schwabe Pharmaceuticals) has been used in most studies (14258,16647,16649,16651,81557,81565,94580,110015,112124). In adults, this specific extract is administered as 30 drops of solution three times daily or in tablet form as 10-30 mg three times daily for 7 days (14258,16649,16651,81557,81565,94580). In children, this specific extract is administered as 10 drops three times daily in patients under 7 years of age or 20 drops three times daily for 7 days in those 7 years of age and older (16651,112124). In children aged 1-5 years of age, this specific extract is also available as a syrup dosed at 2.5 mL 3 times daily, which is equivalent to 10 drops of solution 3 times daily (112123). Some studies used extracts in tablet form; however, these tablet formulations have only been shown to be beneficial in adults, not in children (17417,94580).
• Chronic obstructive pulmonary disease (COPD). Oral Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) may decrease the frequency of exacerbations, improve symptoms, and reduce the need for antibiotics in patients with COPD; however, it does not seem to reduce the overall risk of exacerbations. Details: One clinical study in patients with moderate to severe COPD shows that taking Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 1.5 mL three times daily in addition to standard treatment for 24 weeks lengthens the average time to COPD exacerbation by 14 days when compared with placebo (97319). The addition of Pelargonium sidoides to standard therapy is also associated with a reduction in total COPD symptoms, antibiotic use, and missed workdays (97319,97325). However, Pelargonium sidoides does not seem to decrease the overall number of COPD exacerbations (97325).
• Common cold. Oral Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) may reduce the severity and duration of cold symptoms and improve sleep quality in adults with the common cold. Details: Some clinical research in adults with the common cold shows that taking Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 1.5 mL three times daily reduces symptoms of the common cold and increases the rate of complete resolution after 10 days of treatment, but not after 5 days of treatment, when compared with placebo (81569,94580). The same product taken at a higher dose of 3 mL three times daily reduces cold symptoms by an additional 10% and has a higher rate of complete resolution after 5 days of treatment. However, this dose is associated with a higher rate of mild to moderate adverse effects (97318). Additionally, a small uncontrolled study shows that this extract is equally effective for reducing common cold symptoms in patients testing positive for human coronavirus infection (not including COVID-19) when compared with other viruses (106648). Meta-analyses have evaluated the effects of this specific extract in adults with the common cold. One meta-analysis of 5 studies, some unpublished, using Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals)extract 1.5-3 mL three times daily, or tablets 20-40 mg three times daily, for 10 days shows that the mean reduction in a subjective, 40-point, total cold intensity score is 2.3 points at 5 days and 1.2 points at 10 days. Although it is unclear if these decreases are clinically significant, the extract was associated with fewer lost work days, lower acetaminophen consumption, and improved sleep quality when compared with placebo (103604). A separate meta-analysis of five small-to-moderate size studies, some of which were included in the previous meta-analysis, shows that taking Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) in the same formulations and doses reduces cough intensity and increases remission of cough at day 5 when compared with placebo (110015). However, all outcomes in this meta-analysis were patient-reported. Lastly, a network meta-analysis comparing 18 herbal medicines often used for the common cold suggests that Pelargonium sidoides is the most beneficial of those studied for the relief of symptoms associated with the common cold (112122). However, it is unclear whether any improvements in cold symptoms are clinically significant.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. It is unclear if oral Pelargonium sidoides extract is beneficial in children with asthma who have an active viral upper respiratory tract infection. Details: One small clinical study in children with mild asthma and an active viral upper respiratory tract infection shows that taking 5-10 drops of a specific extract of Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) three times daily for 5 days reduces the number of children experiencing asthma attacks by 28% when compared with no treatment. It also reduces the number of children experiencing nasal symptoms by 34% and cough by 31% when compared with no treatment (94577).
• Genital herpes. Although there has been interest in using oral Pelargonium sidoides for genital herpes, there is insufficient reliable information about the clinical effects of Pelargonium sidoides for this purpose.
• Herpes labialis (cold sores). Although there has been interest in using oral Pelargonium sidoides for herpes labialis, there is insufficient reliable information about the clinical effects of Pelargonium sidoides for this purpose.
• Rhinosinusitis. Small clinical studies suggest that oral Pelargonium sidoides root extract may improve symptoms in adults with rhinosinusitis. Details: One small clinical study in adults with rhinosinusitis of unclear etiology shows that taking Pelargonium sidoides root extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 60 drops three times daily for 21 days reduces symptoms of rhinosinusitis and increases the chance of complete resolution after treatment by 57% when compared with placebo (94580). Additionally, a small open-label study in adults with acute bacterial rhinosinusitus shows that taking this same product in tablet form as 60 mg daily for 10 days reduces the total symptom score, as well as subjective measures of nasal obstruction, facial pain and pressure, impaired sense of smell, mucosal edema, and mucopurulent secretions, when compared with taking amoxicillin 1500 mg daily for 10 days (103605). Additionally, a network meta-analysis comparing 18 herbal medicines often used for acute post-viral rhinosinusitis suggests that Pelargonium sidoides is the most beneficial after cineole for the relief of symptoms (112122).
• Tonsillopharyngitis. It is unclear if oral Pelargonium sidoides extract is beneficial in children with tonsillopharyngitis. Details: A small clinical study in children aged 6-10 years with acute tonsillopharyngitis shows that taking a specific Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 20 drops three times daily for 7 days reduces symptoms such as sore throat and difficulty swallowing after 4 days of treatment when compared with placebo (14262). A meta-analysis of 6 clinical trials in children aged 6-10 years old with acute tonsillopharyngitis or acute bronchitis, including the study mentioned above, shows that taking a specific Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 60-240 drops daily for 6 days reduces the amount of acetaminophen co-medication required to treat fever when compared with placebo (112126).
• Upper respiratory tract infection (URTI). A small clinical study suggests that oral Pelargonium sidoides root extract may improve symptoms in children with URTIs. Details: One clinical trial in children with uncomplicated URTIs shows that taking a specific Pelargonium sidoides root extract (Pelumm) three times daily for 7 days reduces total symptom scores when compared with placebo, with cough frequency and sneezing improving significantly within 3 days of treatment. The extract dose was based on patient age, with children 1-5 years of age taking 10 drops three times daily, children 5-12 years of age taking 20 drops three times daily, and children 13 years of age taking 30 drops three times daily (106646). More evidence is needed to rate Pelargonium sidoides for these uses.

(Read more about PELARGONIUM SIDOIDES)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there is interest in using inhaled Roman chamomile for allergic rhinitis, there is insufficient reliable information about the clinical effects of Roman chamomile for this condition.
• Anxiety. Although there is interest in using inhaled Roman chamomile for anxiety, there is insufficient reliable information about the clinical effects of Roman chamomile for this condition.
• Atopic dermatitis (eczema). Although there is interest in using topical Roman chamomile for atopic dermatitis, there is insufficient reliable information about the clinical effects of Roman chamomile for this condition.
• Burns. Although there is interest in using topical Roman chamomile for burns, there is insufficient reliable information about the clinical effects of Roman chamomile for this purpose.
• Diabetes. Although there is interest in using oral Roman chamomile for diabetes, there is insufficient reliable information about the clinical effects of Roman chamomile for this condition.
• Diaper rash. Although there is interest in using topical Roman chamomile for diaper rash, there is insufficient reliable information about the clinical effects of Roman chamomile for this purpose.
• Dysmenorrhea. Although there is interest in using oral Roman chamomile for dysmenorrhea, there is insufficient reliable information about the clinical effects of Roman chamomile for this condition.
• Dyspepsia. Although there is interest in using oral Roman chamomile for dyspepsia, there is insufficient reliable information about the clinical effects of Roman chamomile for this purpose.
• Hemorrhoids. Although there is interest in using topical Roman chamomile for hemorrhoids, there is insufficient reliable information about the clinical effects of Roman chamomile for this purpose.
• Hypertension. Although there is interest in using oral Roman chamomile for hypertension, there is insufficient reliable information about the clinical effects of Roman chamomile for this condition.
• Insomnia. Although there is interest in using oral or inhaled Roman chamomile for insomnia, there is insufficient reliable information about the clinical effects of Roman chamomile for this purpose.
• Lichen planus. It is unclear if topical Roman chamomile is beneficial in patients with lichen planus. Details: Preliminary clinical research in patients with oral lichen planus shows that applying a Roman chamomile 2% gel, 0.5 mL three times daily for 4 weeks, reduces pain, itching, and burning when compared with placebo. Chamomile was associated with a total response in 19% of patients, and a partial response in 73%, compared with partial responses in only 17% of patients receiving placebo (107369).
• Nausea and vomiting. Although there is interest in using oral Roman chamomile for nausea and vomiting, there is insufficient reliable information about the clinical effects of Roman chamomile for this purpose.
• Pruritus. It is unclear if Roman chamomile is beneficial for pruritis. Details: A moderate-sized quasi-experimental clinical study in older females with pruritis shows that applying a mixture of Roman chamomile, lavender, and sandalwood diluted to 1.5% in sweet almond oil during a massage three times weekly for 1 month modestly improves pruritis when compared with sandalwood oil during massage, but does not improve skin pH or level of hydration (112365). It is unclear if these findings are due to Roman chamomile, other ingredients, or the combination.
• Rheumatoid arthritis (RA). Although there is interest in using topical Roman chamomile for RA, there is insufficient reliable information about the clinical effects of Roman chamomile for this condition.
• Stress. It is unclear if Roman chamomile is beneficial for stress. Details: A moderate-sized quasi-experimental clinical study in older females shows that applying a mixture of Roman chamomile, lavender, and sandalwood diluted to 1.5% in sweet almond oil during a massage three times weekly for 1 month marginally improves the level of self-reported stress when compared with sandalwood oil during massage (112365). It is unclear if this finding is due to Roman chamomile, other ingredients, or the combination.
• Wound healing. Although there is interest in using topical Roman chamomile for wound healing, there is insufficient reliable information about the clinical effects of Roman chamomile for this purpose. More evidence is needed to rate Roman chamomile for these uses.

(Read more about ROMAN CHAMOMILE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Hereditary hemorrhagic telangiectasia (HHT). It is unclear if topical rose geranium oil is beneficial for epistaxis in patients with HHT. Details: A small clinical study in patients with HHT shows that applying 3-4 drops of a topical formulation containing rose geranium essential oil 0.17% in sesame oil into the nose twice daily for at least 3 months reduces the severity of epistaxis by 34% when compared to baseline (93881). The validity of this finding is limited by a lack of control group.
• Neuropathic pain. Although there has been interest in using oral and topical rose geranium oil for neuropathic pain, there is insufficient reliable information about the clinical effects of rose geranium oil for this purpose.
• Postherpetic neuralgia. It is unclear if topical rose geranium oil is beneficial in patients with postherpetic neuralgia. Details: A small clinical study in patients with postherpetic neuralgia shows that a single topical application of rose geranium oil 50% or 100% can significantly reduce pain when compared with placebo. Pain relief appears to be concentration-dependent. Rose geranium oil in a concentration of 100% appears to be about twice as effective as a 50% concentration (16653).
• Wound healing. Although there has been interest in using topical rose geranium oil for wound healing, there is insufficient reliable information about the clinical effects of rose geranium oil for this purpose. More evidence is needed to rate rose geranium oil for these uses.

(Read more about ROSE GERANIUM OIL)

There is insufficient reliable information available about the effectiveness of spotted geranium.

(Read more about SPOTTED GERANIUM)

POSSIBLY EFFECTIVE

• Mastalgia. Meta-analyses of small clinical studies show that vitex agnus-castus moderately reduces breast pain due to cyclic mastalgia. Details: Two small meta-analyses of low-to-moderate quality clinical studies in patients with cyclic mastalgia show that taking vitex agnus-castus moderately reduces breast pain when compared with placebo (101981,111753). The validity of these findings is limited by the heterogeneity of the included studies. Doses of vitex agnus-castus dried fruit extract range from 3.2-40 mg daily, for 2-6 months (90617,96250,101981,111753). Vitex agnus-castus is commonly used in proprietary products, alone or in combination with other herbs (Agnucaston/Cyclodynon, Bionorica AG, Femicur, Mastodynon, Bionorica AG, Monoselect Agnus, ZE 440) (13395).
• Premenstrual syndrome (PMS). Clinical research shows that vitex agnus-castus produces modest improvements in PMS symptoms. Details: Clinical research shows that taking vitex agnus-castus fruit extract orally for 2-6 menstrual cycles seems to reduce symptoms of PMS, especially breast pain or tenderness (mastalgia), edema, constipation, irritability, depressed mood, anxiety, anger, and headache (7055,7076,7078,7079,13394,15065,41483,41489,41490,41494,90619,101981). Doses of fruit extracts have varied from 3.5-40 mg daily, usually for 2-3 menstrual cycles (7055,7076,7078,7079,15065,41483,41489,41490,90619,96435). A meta-analysis of the available clinical research, including 17 studies involving 2,401 patients, shows that taking vitex agnus-castus is comparable to fluoxetine or oral contraceptives, and modestly more effective than placebo, for reducing the symptoms of PMS. A sub-group analysis indicates that efficacy is not impacted by the dose or form used, although the dried powdered berries appear to be ineffective. The low quality of the included studies and the high level of bias and heterogeneity limit the validity of these findings (96435). Another meta-analysis limited to three randomized controlled trials shows that taking vitex agnus-castus increases the likelihood of PMS symptom remission by 2.6-fold over placebo (101979). Some clinical studies have used a specific dried extract of vitex agnus-castus fruit (Agnolyt, Madaus AG) (7076). Other studies used a specific fruit extract known as Ze 440 (Prefemin, Zeller AG), which is standardized to casticin content (7078,90619). Additional studies have used the fruit extract BNO 1095 (Agnucaston/Cyclodynon, Bionorica AG) (15065,41483,41489,41490).

POSSIBLY INEFFECTIVE

• Fractures. Limited evidence suggests that vitex agnus-castus does not improve fracture healing rates. Details: Clinical research shows that taking a specific vitex agnus-castus dried fruit extract (Agnugol, Goldaru Pharmacy Company) 4 mg, alone or in combination with magnesium oxide (Nature Made Company) 250 mg, daily for 8 weeks does not improve long bone fracture healing when compared with placebo (90618).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using oral vitex agnus-castus for acne, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Aging skin. Vitex agnus-castus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical trial in postmenopausal adults with wrinkles shows that taking one capsule orally daily of a combination of vitex agnus-castus 400 mg, evening primrose oil 500 mg, soy isoflavones 100 mg, and black cohosh 520 mg (Estosalus, Max Biocare Pty Ltd) for 12 weeks improves skin elasticity, skin smoothness, and wrinkle density scores when compared with placebo (109440).
• Amenorrhea. Although there is interest in using oral vitex agnus-castus for amenorrhea, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Anxiety. Although there is interest in using oral vitex agnus-castus for anxiety, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Benign prostatic hyperplasia (BPH). Although there is interest in using oral vitex agnus-castus for BPH, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Dementia. Although there is interest in using oral vitex agnus-castus for dementia, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Dysmenorrhea. It is unclear if oral vitex agnus-castus is beneficial in patients with dysmenorrhea. Details: Preliminary clinical research in patients with primary dysmenorrhea shows that taking a specific vitex agnus-castus extract (Agnucaston, Bionorica AG) daily for 3 months reduces pain, as measured on a visual analog scale, similarly to ethinyl estradiol 0.03 mg / drospirenone 3 mg (Yasmin) taken daily (104975).
• Fibrocystic breast disease. Although there is interest in using oral vitex agnus-castus for fibrocystic breast disease, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Hyperprolactinemia. Although there is interest in using oral vitex agnus-castus for hyperprolactinemia, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Infertility. It is unclear if oral vitex agnus-castus is beneficial for female infertility. Details: Preliminary clinical research in infertile females with oligomenorrhea or amenorrhea shows that taking homeopathic vitex agnus-castus (Phyto Hypophyson L, Steierl-Pharma GmbH) 50 drops orally three times daily for 3 months does not increase the chance of getting pregnant (41470). Also, one small clinical study in those with infertility due to secondary amenorrhea or luteal insufficiency shows that taking a vitex agnus-castus preparation (Mastodynon, Bionorica GmbH, Neumarkt/Opf.) 30 drops twice daily for at least 3 months does not increase the chance of pregnancy when compared with placebo, although the study was likely inadequately powered to detect a difference (7077).
• Insect repellent. Limited research suggests that topical vitex agnus-castus has insect repellent activity. Details: Preliminary clinical research shows that applying a carbon dioxide extract of vitex agnus-castus seeds seems to repel ticks and fleas for 6 hours, mosquitoes for 3-8 hours, and biting flies for 3 hours (13396). It is unclear how this compares with commonly used insect repellants.
• Insomnia. Although there is interest in using oral vitex agnus-castus for insomnia, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Lactation. Although there is interest in using oral vitex agnus-castus for stimulating lactation, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Menopausal symptoms. Clinical research suggests that vitex agnus-castus can relieve some menopausal symptoms; however, most research uses vitex agnus-castus in combination with other treatments. Details: Clinical research shows that taking vitex agnus-castus extract 15 mg twice daily for 8 weeks improves some menopausal symptoms, including anxiety and vasomotor dysfunction, by 76% and 88%, respectively, when compared with baseline. However, there was no effect on depression or sexual dysfunction (101980). Vitex agnus-castus has also been studied as a component of combination products. Preliminary clinical research shows that taking a combination of vitex agnus-castus, equivalent to 1000 mg dried fruit, black seed powder 500 mg, and citalopram 20 mg daily for 8 weeks reduces vasomotor, psychosocial, and physical symptoms of menopause when compared with citalopram alone (100325). Other preliminary clinical research shows that taking one capsule orally daily of a combination of vitex agnus-castus 400 mg, evening primrose oil 500 mg, soy isoflavones 100 mg, and black cohosh 520 mg (Estosalus, Max Biocare Pty Ltd) for 12 weeks moderately reduces the severity of hot flashes, sweating, sleep problems, depressed mood, and irritability when compared with placebo. There was no effect on plasma lipids, joint discomfort, anxiety, exhaustion, or sexual problems (105102). It is unclear if these effects are due to vitex agnus-castus, other ingredients, or the combination.
• Menorrhagia. It is unclear if oral vitex agnus-castus is beneficial in patients with menorrhagia. Details: A meta-analysis of two moderate quality clinical trials in patients who had heavy menstrual periods shows that taking vitex agnus-castus does not reduce menstrual bleeding over the next 1-2 menstrual cycles when compared with placebo (101982). However, preliminary clinical research in patients using an intrauterine device (IUD) shows that taking vitex agnus-castus three times daily for 8 days, starting on the first day of menstruation, and repeated for four consecutive menstrual cycles, reduces the amount of bleeding by approximately 48% when compared with baseline. This reduction was similar to the effects of mefenamic acid 250 mg daily after 4 months, although treatment with mefenamic acid was superior during the first three months (90620).
• Migraine headache. Although there is interest in using oral vitex agnus-castus for migraine headache, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Polycystic ovary syndrome (PCOS). Vitex agnus-castus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with oligomenorrhea due to PCOS shows that taking a traditional combination product (Aslagh) containing equivalent amounts of essential oils of vitex agnus-castus fruit, fennel, and wild carrot seeds orally daily for 3 months, either alone or in combination with metformin, improves rates of menstrual bleeding and menstrual cyclicity similarly to metformin alone. All three groups experienced a significant improvement from baseline. Aslagh was taken as two, 500-mg capsules twice daily, except during menses; metformin was titrated over one week to a dose of 500 mg three times daily (108974).
• Premenstrual dysphoric disorder (PMDD). Limited evidence suggests that vitex agnus-castus might improve symptoms of PMDD. Details: In a clinical trial, vitex agnus-castus 20-40 mg daily for 8 weeks was similar to fluoxetine 20-40 mg daily for relieving symptoms of PMDD. About 58% of patients responded to vitex agnus-castus, compared to about 68% of patients taking fluoxetine. Vitex agnus-castus was more effective for physical symptoms such as breast tenderness, swelling, cramps, and food cravings (12207,41493).
• Rheumatoid arthritis (RA). Although there is interest in using oral vitex agnus-castus for RA, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Sexual dysfunction. It is unclear if oral vitex agnus-castus is beneficial in patients with sexual dysfunction. Details: Preliminary clinical research in healthy females under 44 years of age with sexual dissatisfaction shows that taking a specific vitex agnus-castus product (Agnugol, Goldaru Herbal Pharmaceutical Company) 3.2-4.8 mg orally once daily for 16 weeks modestly improves scores of sexual satisfaction, function, arousal, and desire when compared with placebo (109437). Additionally, a moderate-sized clinical study in females 50-69 years old with sexual dysfunction conducted in Iran shows that taking vitex agnus-castus 40 drops daily for 8 weeks improves sexual dysfunction scores from mild dysfunction to no dysfunction at 6 and 8 weeks when compared with placebo but does not improve scores at 4 weeks (112361). More evidence is needed to rate the effectiveness of vitex agnus-castus for these uses.

(Read more about VITEX AGNUS-CASTUS)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cognitive function. It is unclear if ylang ylang oil aromatherapy is beneficial in improving cognitive function. Details: Preliminary clinical research in healthy adults shows that aromatherapy with ylang ylang oil once for 5 minutes before and during a cognitive test does not improve working memory or attention, and may actually worsen speed of memory, when compared with no aromatherapy (98616).
• Hypertension. Although there has been interest in using topical ylang ylang oil for hypertension, there is insufficient reliable information about the clinical effects of ylang ylang oil for this purpose.
• Lice. Topical ylang ylang oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children aged 6-14 years shows that applying a topical spray containing ylang ylang oil, anise oil, and coconut three times at 15 minute intervals every 5 days is 92% effective at eradicating head lice. These results were similar to a control spray containing permethrin, malathion, piperonyl butoxide, and isododecane (13483).
• Suicidal ideation. It is unclear if ylang ylang oil aromatherapy is beneficial in patients with suicidal ideation. Details: Low-quality clinical research in patients with a history of suicidal ideation or attempts shows that 1-5 sessions of either spiritual support or a massage with ylang ylang oil 10% aromatherapy over 4 months reduces the rate of suicide or suicide attempts by 75% when compared with a control group (109499). The validity of these results is limited by lack of randomization. More evidence is needed to rate ylang ylang oil for these uses.

(Read more about YLANG YLANG OIL)

LIKELY UNSAFE ...when used orally. 1,3-DMAA is a drug originally used as a stimulant nasal decongestant. There is concern that it increases the risk of serious adverse cardiovascular events, similar to other stimulants such as synephrine in bitter orange and ephedrine alkaloids from ephedra. There are several case reports linking 1,3-DMAA to serious adverse events including lactic acidosis, hemorrhagic stroke, heat stroke, and death (17599,17660,17662,17663,17904,94361,94369,94374). Although some supplement manufacturers claim that 1,3-DMAA is a natural compound found in geranium oil, this has not been verified by laboratory analysis. Some laboratories have not been able to detect 1,3-DMAA in geranium oil (94370,94372). There is concern that some supplement manufacturers may be artificially spiking their supplements with this synthetic drug (17661,17662). The New Zealand government restricted sales of supplements containing 1,3-DMAA to prevent the sale to people under 18 years of age due to concerns about safety (17599). The FDA has declared products containing 1,3-DMAA to be illegal and potential health risks (94383). Avoid using.

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

(Read more about 1,3-DMAA)

LIKELY SAFE ...when bergamot essential oil is used orally in amounts commonly found in foods. Bergamot oil has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).

POSSIBLY SAFE ...when bergamot extract is used orally, short-term. A bergamot extract (Bergamot Polyphenolic Fraction BPF, H&AD SRL) has been used with apparent safety at a dose of 650 mg daily for up to 120 days (96355,105318). Another bergamot extract providing 150 mg of flavonoids (Bergavit, Bionap) daily has been used with apparent safety for up to 6 months (102599). Bergamot phytosome (Vazguard, Indena SpA) has been used with apparent safety at a dose of 500 mg twice daily for 12 weeks (105317). ...when inhaled as aromatherapy, short-term. Bergamot oil 3% has been used with apparent safety as 2 drops poured on a cotton ball, attached to the collar, and breathed in for 20 minutes (105319).

POSSIBLY UNSAFE ...when used topically. Bergamot essential oil that is not free of furocoumarins or psoralens can act as a photosensitizer and can induce malignant changes (6,96370).

CHILDREN: LIKELY SAFE
when bergamot essential oil is used orally in amounts commonly found in foods. Bergamot oil has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).

CHILDREN: POSSIBLY UNSAFE
when large amounts of the oil are ingested. Bergamot essential oil can cause intestinal colic, convulsions, and death (12). There is insufficient reliable information available about the safety of bergamot extract when used orally.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when the oil is used topically (6). There is insufficient reliable information available about the safety of bergamot when taken by mouth in medicinal amounts; avoid use.

(Read more about BERGAMOT)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Clary sage has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912). There is insufficient reliable information available about the safety of clary sage when used as medicine.

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

(Read more about CLARY SAGE)

POSSIBLY UNSAFE ...when used orally in large amounts (exact dose not specified). Overdose of Eastern red cedar essential oil has been associated with vomiting, convulsions, coma, and fatality (12). There is insufficient reliable information available about the safety of Eastern red cedar when used orally in smaller amounts or when applied topically.

PREGNANCY: LIKELY UNSAFE
when used orally. Eastern red cedar is contraindicated in pregnancy due to reports of abortifacient activity. The specific part or dose of Eastern red cedar associated with its abortifacient activity is unclear (12); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about EASTERN RED CEDAR)

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

POSSIBLY SAFE ...when fennel essential oil or extract is used orally and appropriately, short-term. Twenty-five drops (about 1.25 mL) of fennel fruit extract standardized to fennel 2% essential oil has been safely used four times daily for 5 days (49422). Also, two 100 mg capsules each containing fennel 30% essential oil standardized to 71-90 mg of anethole has been safely used daily for 8 weeks (97498). Powdered fennel extract has been used with apparent safety at a dose of 800 mg daily for 2 weeks (104199). ...when creams containing fennel 2% to 5% are applied topically (49429,92509).

CHILDREN: POSSIBLY SAFE
when combination products containing fennel are used to treat colic in infants for up to one week. Studied products include up to 20 mL of a fennel seed oil emulsion; a specific product (ColiMil) containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg; and up to 450 mL of a specific tea (Calma-Bebi, Bonomelli) containing fennel, chamomile, vervain, licorice, and lemon balm (16735,19715,49428).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Observational research has found that regular use of fennel during pregnancy is associated with shortened gestation (100513).

LACTATION: POSSIBLY UNSAFE
when used orally. Case reports have linked consumption of an herbal tea containing extracts of fennel, licorice, anise, and goat's rue to neurotoxicity in two breast-feeding infants. The adverse effect was attributed to anethole, a constituent of fennel and anise (16744). However, levels of anethole were not measured in breastmilk, and the herbal tea was not tested for contaminants. Furthermore, other adverse effects related to use of fennel during lactation have not been reported. However, until more is known, avoid using.

(Read more about FENNEL)

LIKELY SAFE ...when used orally or appropriately, short-term. A specific extract of Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals), in doses of 4.5-9 mL daily when administered as a solution or 90 mg daily when administered as a tablet, has been safely used for up to 24 weeks (14258,16641,16647,16649,16651,17417,81557,81565,94580,97318)(97319,106647). There is insufficient reliable information available about the safety of Pelargonium sidoides when used orally, long-term.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. A specific extract of Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) in doses of 3 mL daily has been used with apparent safety in children aged 6-10 years for up to 7 days (14262,16641,16651,17417,94580).

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

(Read more about PELARGONIUM SIDOIDES)

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

POSSIBLY SAFE ...when used topically as a 2% gel for up to 4 weeks (107369). ...when the essential oil is inhaled or used topically as aromatherapy (7107). There is insufficient reliable information available about the safety of Roman chamomile when used orally in amounts greater than those found in foods.

PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts. Roman chamomile is believed to be an abortifacient (4). Some population research has found a possible link between the use of Roman chamomile and an increased incidence of reduced birth weight, threatened miscarriage, and preterm labor (97292). There is insufficient reliable information available about the safety of the topical use of Roman chamomile during pregnancy; avoid using.

LACTATION:
Insufficient reliable information available; avoid using (4).

(Read more about ROMAN CHAMOMILE)

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

POSSIBLY SAFE ...when used topically and appropriately, short-term. A single application of rose geranium oil in concentrations up to 100% has been safely used in a clinical trial (16653). ...when used intranasally and appropriately, short-term. Rose geranium oil has been applied with sesame oil in the nose safely (93881). There is insufficient reliable information available about using rose geranium oil orally for medicinal purposes.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid amounts greater than those found in foods.

(Read more about ROSE GERANIUM OIL)

There is insufficient reliable information available about the safety of spotted geranium.

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

(Read more about SPOTTED GERANIUM)

LIKELY SAFE ...when the fruit extract is used orally and appropriately, short-term. Vitex agnus-castus fruit extract has been used safely in studies at doses up to 40 mg daily, for up to 3 months (7055,7076,7077,7078,7079,12207,13393,15065,90617,90618,96435). There is insufficient reliable information available about the safety of vitex agnus-castus seeds when used orally or topically.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally. Theoretically, the hormonal effects of vitex agnus-castus might adversely affect pregnancy or lactation (10979,11456,13393,109439). Animal research shows that taking vitex agnus-castus fruit extract when planning to become pregnant or during pregnancy may increase the risk of infertility, low fetal body weight, abortion, and stillbirth (109439); avoid using.

(Read more about VITEX AGNUS-CASTUS)

LIKELY SAFE ...when used in amounts commonly found in foods. Ylang ylang oil has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of ylang ylang oil when used orally or topically in medicinal amounts.

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in food. Ylang ylang oil has Generally Recognized as Safe (GRAS) status in the US (4912).

CHILDREN: POSSIBLY SAFE
when used topically. Ylang ylang oil has been used with apparent safety as three applications to the scalp at 5-day intervals (13483). There is insufficient reliable information available about the safety of ylang ylang oil when used orally in medicinal amounts in children.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food. Ylang ylang oil has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of using ylang ylang oil in medicinal amounts.

(Read more about YLANG YLANG OIL)

(Read more about 1,3-DMAA)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking bergamot with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research suggests that bergamot juice has hypoglycemic effects (34407).

PHOTOSENSITIZING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, topical bergamot essential oil might increase the risk of side effects when used along with photosensitizing drugs.  Details Bergamot contains bergapten, which has photosensitizing effects (11019,34343,34350,34363,34377,34408,34410,34417,34421,34422,34426,34428).

(Read more about BERGAMOT)

(Read more about CLARY SAGE)

(Read more about EASTERN RED CEDAR)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details Animal research suggests that fennel oil has antithrombotic and antiplatelet effects (31415,49445).

CIPROFLOXACIN (Cipro) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.  Details Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin (6135).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.  Details In vitro research suggests that fennel inhibits CYP3A4 enzyme activity (38375,49468). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.  Details Some constituents of fennel have estrogenic activity (11), which may interfere with the antiestrogenic activity of tamoxifen.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, Pelargonium sidoides might increase the risk of bleeding when taken with anticoagulant and antiplatelet drugs.  Details Pelargonium sidoides contains coumarin, which may reduce platelet aggregation (14259). However, in animal models, Pelargonium sidoides extract does not appear to inhibit coagulation or interact with warfarin (16648). This interaction has not been documented in humans.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Pelargonium sidoides might decrease the effectiveness of immunosuppressant therapy.  Details In vitro research suggests that Pelargonium sidoides has immunostimulant effects (14258,14259,16646,16650,16652).

(Read more about PELARGONIUM SIDOIDES)

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ANTIPSYCHOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, vitex agnus-castus could interfere with the activity of antipsychotic drugs.  Details Vitex agnus-castus might interfere with the action of dopamine antagonists such as antipsychotic drugs due to its dopamine agonist effects (7014,7015).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, vitex agnus-castus could interfere with oral contraceptives.  Details Vitex agnus-castus might interfere with the efficacy of oral contraceptives due to possible hormone modulating activity (10979,11456).

DOPAMINE AGONISTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, vitex agnus-castus could interfere with dopamine agonists.  Details Vitex agnus-castus might potentiate the actions of dopaminergic agonists due to possible dopaminergic effects (10122).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, vitex agnus-castus could interfere with the activity of estrogens.  Details Vitex agnus-castus has hormone modulating activity that can interfere with the efficacy of hormone replacement therapy (10979,11456).

METOCLOPRAMIDE (Reglan) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dopaminergic effects of vitex agnus-castus could interfere with metoclopramide.  Details Vitex agnus-castus might interfere with the action of dopamine antagonists such as metoclopramide due to its possible dopaminergic effects (7014,7015).

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General ...Orally, taking 1,3-DMAA combination products (OxyELITE Pro, AmphetaLean, or Jack3d, USPlabs) has been reported to cause cardiac arrest, atrial fibrillation, chest pressure, angina, tachycardia, palpitations, hypertension, hypotension, myocardial infarction, and acute coronary syndrome (17660,91680,94361,94362,94365,94369,94371,94377). Increased heart rate and blood pressure have also been reported. Other reported adverse effects associated with the use of 1,3-DMAA-containing products have included life-threatening lactic acidosis (17660), nausea, vomiting, diarrhea, and abdominal pain (17663,17907,17908,94365,94371,94377), urinary changes (17663,94365,94371,94377), liver injury (94367,94368,94369), anaphylaxis (94365), muscle symptoms such as spasm or weakness (94377), neurological symptoms including tremors, insomnia, sweating, tiredness, confusion, headache, and chills (17907,17663), hemorrhagic stroke (17663,90318), pupil dilation or tinnitus (94365,94371), psychiatric symptoms such as anxiety, agitation, paranoia, and aggression (17660,17907,94365,94371,94377), or rapid breathing (17660,94371). The dose of 1,3-DMAA at which such adverse effects occur is not clear (94368).
Death has occurred in some cases following organ failure and cardiac arrest (17904,94361,94369,94374).
Topically, rubbing an eye while mixing a drink with a 1,3-DMAA-containing combination product (Jack3d) has caused pupil dilation (94368).

Cardiovascular ...Due to the stimulant effects of 1,3-DMAA, there is concern that it might increase the risk of adverse cardiovascular events similar to synephrine from bitter orange or ephedrine from ephedra. Cardiovascular outcomes have rarely been assessed in patients taking 1,3-DMAA alone. Most adverse effects are linked to 1,3-DMAA-containing combination products. Palpitations and tachycardia are some of the most common side effects reported for adults and children taking 1,3-DMAA-containing combination products (17660,91680,94365,94371). Other less common adverse effects have included chest pressure, angina, atrial fibrillation, hypertension, hypotension, myocardial infarction, and acute coronary syndrome (17660,91680,94362,94365,94371,94377).
There is inconsistent data about the effects of 1,3-DMAA on heart rate and blood pressure (94368). For example, some research suggests that taking specific 1,3-DMAA-containing combination products (OxyELITE Pro or Jack3d, USPlabs) significantly increases systolic blood pressure and increases heart rate within 1-2 hours of taking a dose. These increases appear to be dose dependent (17906,17907,17908). However, in an 8-week study, heart rate was significantly increased, but blood pressure was not (17907). Other research shows that neither acute nor chronic intake of 1,3-DMAA increases heart rate or blood pressure (17908,94364,94368,94376). Overall, it seems that oral intake of a single dose of a 1,3-DMAA-containing product is more likely to increase systolic blood pressure. Resting blood pressure is less likely to remain increased following chronic use (94368,94379). Higher doses are more likely to increase heart rate and blood pressure. Although most sports supplements contain 25-65 mg/dose, some contain as much as 285 mg/dose (94377).
In case reports of healthy young adults taking 1,3-DMAA-containing combination products prior to exercise, cardiac arrest causing death has occurred (94361,94369).

Endocrine ...In one report, a patient who took a specific combination product containing 1,3-DMAA (Jack3d by USP Labs) prior to intense exercise experienced life-threatening lactic acidosis (17660).

Gastrointestinal ...Orally, taking 1,3-DMAA-containing combination products has been reported to cause nausea (17907,17908,94365,94371,94377), vomiting (17663,94365,94371,94377), diarrhea (94365), vomiting blood (94371), and abdominal pain (94371).

Genitourinary ...Urinary hesitancy (94365), urinary retention (94371), and uncontrolled urination (94377), have been reported following ingestion of 1,3-DMAA-containing combination products.

Hepatic ...Acute liver injury, in some cases requiring a liver transplant, has been reported following oral intake of 1,3-DMAA-containing products (94367,94368,94369).

Immunologic ...An anaphylactic reaction has been reported following oral intake of 1,3-DMAA-containing products (94365).

Musculoskeletal ...Orally, dimethylamine-containing products have caused muscle spasm (94365), muscle weakness (94377), and leg pains (94377).

Neurologic/CNS ...Orally, taking specific 1,3-DMAA-containing combination products (OxyELITE Pro or Jack3d, USPlabs) has been reported to cause feelings of jitters, sleeplessness, shakiness, chills, sweating, fatigue, tingling, and lack of focus in clinical trials (17907). Other adverse effects reported for products containing 1,3-DMAA have included headache, dizziness, tremor, numbness, flushing, seizure, blacking out, visual disturbances, confusion, and lethargy (17660,17908,94365,94368,94371,94377). In a case report, a 26 year old male reported with a hemorrhagic stroke linked to taking the supplement Jack3d, which contains 1,3-DMAA, schizandrol A, caffeine, beta-alanine, creatine, and L-arginine alpha-ketoglutarate (90318). In another report, a patient experienced a hemorrhagic stroke after taking two tablets of a product containing 1,3-DMAA 278 mg each along with caffeine 150 mg and a can of beer (17663).

Ocular/Otic ...Orally, dimethylamine-containing products have caused tinnitus (94365) and pupil dilation (94371). Pupil dilation also occurred after rubbing an eye while mixing a drink with the specific product Jack3d, containing 1,3-DMAA (94368).

Psychiatric ...Orally, taking 1,3-DMAA-containing combination products has been reported to cause feelings of anxiety (17907,94365), suicidal behavior (94365), agitation or irritability (94365,94371,94377), paranoia (94377), depression (94377), panic (94377), and aggression or combativeness (17660,94365).

Pulmonary/Respiratory ...Orally, combination products containing 1,3-DMAA have caused rapid breathing and hyperventilation (17660,94371).

Other ...There are at least two reports of death in US Army soldiers who took 1,3-DMAA supplements and suffered heat stroke and related complications following physical fitness training (17904).

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General ...Orally or as aromatherapy, bergamot seems to be well tolerated when used short-term. Topically, bergamot is possibly unsafe.
Most Common Adverse Effects:
Topically: Blisters, erythema, photosensitivity, pigment spots, pustules, and skin lesions.

Dermatologic ...Frequent contact with the peel or oil of bergamot can cause erythema, blisters, pustules, dermatoses leading to scab formation, and pigment spots (18).
Topically, photosensitivity can also occur, especially in fair-skinned people (11019).

Gastrointestinal ...Orally, bergamot extract has been associated with one case of heartburn in clinical research (96356).

Musculoskeletal ...Orally, muscle cramps have been reported for a patient starting one week after switching from drinking 4 liters of black tea to drinking 4 liters of Earl Grey tea daily. The muscle cramps were attributed bergapten, a constituent of bergamot essential oil in Earl Grey tea. The patient's symptoms subsided after discontinuing Earl Grey tea intake and remained absent upon re-initiation of Earl Grey tea intake 1 liter daily (34344).

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General ...No adverse effects reported. However, a thorough evaluation of safety outcomes has not been conducted.

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General ...Orally, overdose of Eastern red cedar oil might cause burning in the stomach, vomiting, convulsions, coma, and death (12). Topically, Eastern red cedar oil might cause local allergic reactions and irritation; however, several clinical assessments of safety show that applying Eastern red cedar oil topically does not cause skin sensitization or irritation (11,98802).

Dermatologic ...Eastern red cedar oil might cause local allergic reactions and irritation when used topically; however, sevearl clinical assessments of safety show that applying Eastern red cedar oil topically does not cause skin sensitization or irritation(11,98802).

Gastrointestinal ...Orally, overdose of Eastern red cedar oil (dose not specified) might cause burning in the stomach and vomiting (12).

Neurologic/CNS ...Orally, overdose of Eastern red cedar oil (dose not specified) might cause convulsions, coma, and death (12).

(Read more about EASTERN RED CEDAR)

General ...Orally and topically, fennel seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, photosensitivity, and allergic reactions in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Seizures.

Dermatologic ...Advise patients to avoid excessive sunlight or ultraviolet light exposure while using fennel (19). Allergic reactions affecting the skin such as atopic dermatitis and photosensitivity may occur in patients who consume fennel (6178,49507).

Gastrointestinal ...Orally, fennel may cause gastrointestinal complaints, including nausea and vomiting (19146,104196).

Hematologic ...Methemoglobinemia has been reported in four infants following intoxication related to ingestion of a homemade fennel puree that may have been made from improperly stored fennel (49444).

Immunologic ...A case report describes an 11-year-old male who developed an allergy to fennel-containing toothpaste. Immediately after using the toothpaste, the patient experienced sneezing, coughing, itchy mouth, rhinorrhea, nasal congestion, wheezing, difficulty breathing, and palpitations, which resolved within 10 minutes of spitting out the toothpaste and rinsing the mouth. In challenge tests, the patient reacted to chewing fresh fennel root, but not ground fennel seeds (103822).

Neurologic/CNS ...Orally, fennel oil has been associated with tonic clonic and generalized seizures (12868). New-onset cluster headaches are reported in a 24-year-old female while using a toothpaste containing fennel and camphor for 3 months. The headaches resolved upon stopping the toothpaste (112368). It is unclear if this adverse effect can be attributed to fennel, camphor, or the combination.

Pulmonary/Respiratory ...Orally, fennel and fennel seed have been reported to cause bronchial asthma (49478).

(Read more about FENNEL)

General ...Orally, Pelargonium sidoides is generally well tolerated.
Most Common Adverse Effects:
Orally: Allergic skin rash, diarrhea, gastrointestinal upset.

Cardiovascular ...Orally, Pelargonium sidoides has been reported to cause small increases in body temperature and pulse during clinical trials (16649,17417).

Dermatologic ...Orally, Pelargonium sidoides has been associated with allergic skin rash (14262,81557).

Gastrointestinal ...Orally, Pelargonium sidoides has been associated with gastrointestinal upset and diarrhea (14262,81557,97318,97319,106647,112123).

Hematologic ...Orally, Pelargonium sidoides has been associated with epistaxis in one clinical trial (97318).

Hepatic ...Orally, Pelargonium sidoides does not appear to cause hepatotoxicity. Evaluations of hepatotoxicity cases in patients taking Pelargonium sidoides show it was only possibly associated in 4 of the 28 reported cases. In the remaining 24 cases, Pelargonium sidoides was unlikely to be the cause of hepatotoxicity, or was excluded as the cause. Other causes of hepatotoxicity in these cases included infectious disease, pre-existing liver disease, acute pancreatitis, and hepatotoxicity due to conventional medication use (94578,94579).

Immunologic ...Orally, Pelargonium sidoides has been associated with over 34 reports of allergic reactions (81567). Urticaria is the most common reaction but there were also cases of conjunctivitis, rhinitis, and systemic allergic reactions including bronchospasm, dyspnea, tachycardia, and circulatory failure (16651,81567).

(Read more about PELARGONIUM SIDOIDES)

General ...Roman chamomile is generally well tolerated.
Most Common Adverse Effects:
Topically: Allergic skin reactions.

Dermatologic ...Topically, Roman chamomile can cause contact dermatitis (4,567,97292). Allergic skin reactions can occur in up to 20% of individuals exposed to Roman chamomile (19). Multiple case reports have described the development of topical allergic reactions, including eczema and rash, with the use of cleaning products and cosmetics containing chamomile oil or chamomile extract (97292). In one case report, a 55-year-old man experienced disseminated erythroderma with itchy, scaly lesions after non-contact exposure to an area containing many plant varieties. Patch testing confirmed the presence of allergenicity to Roman chamomile (97292).

Gastrointestinal ...Orally, large amounts of Roman chamomile might cause vomiting, although data are conflicting (11,12).

Immunologic ...Allergic skin reactions can occur in up to 20% of individuals exposed to Roman chamomile (19). Cross-sensitivity can occur in individuals with sensitivity to the Asteraceae/Compositae family (19,97292). Multiple case reports have described the development of topical and respiratory allergic reactions with the use of cleaning products and cosmetics containing chamomile oil or chamomile extract (97292).

Pulmonary/Respiratory ...A case report describes the development of cough and rhinitis in a 20-year-old female after exposure to chamomile-scented toilet paper. Skin prick testing confirmed the presence of allergenicity to the toilet paper product (97292).

(Read more about ROMAN CHAMOMILE)

General ...Orally, rose geranium oil is well tolerated when used in food amounts. Topically, rose geranium oil seems to be well tolerated, short-term.

Dermatologic ...Topically, rose geranium oil has been associated with reports of dermatitis in hypersensitive individuals and burning sensations when applied to the face (16653).

Gastrointestinal ...When applied with droppers in the nose, rose geranium oil has been reported to cause a bad taste (93881).

Neurologic/CNS ...Topically, rose geranium oil has been associated with reports of lightheadedness and eye irritation when applied to the face (16653).

Ocular/Otic ...Topically, rose geranium oil has been associated with reports of eye irritation when applied to the face (16653).

(Read more about ROSE GERANIUM OIL)

General ...No adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.

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General ...Orally, vitex agnus-castus is generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, fatigue, headache, insomnia, irregular menstruation, nausea, skin irritation, stomach pain, vomiting.

Dermatologic ...Orally, skin conditions such as itching, irritation, urticaria, rash, acne, eczema, and hair loss have been reported (7055,7076,7078,7079,12207,13393,15065,90617,90619,101981).

Gastrointestinal ...Orally, gastrointestinal upset or pain, diarrhea, and nausea and vomiting, have been reported (7079,12207,13393,15065,90620,101981,101982). In one clinical trial, a single patient reported persistent gastroenteritis while taking vitex agnus-castus (7076). Orally, development of a bezoar resulting in colonic obstruction is described in a 63-year-old male who consumed an unknown amount of vitex agnus-castus seeds (111752).

Genitourinary ...Orally, irregular or prolonged menstrual bleeding has been reported (7055,7079,12207,13393,15065,41489,41490,95326).

Hematologic ...Orally, nosebleed has been reported in a single patient in a clinical trial (7079).

Immunologic ...Orally, multiple abscesses have been reported in a single patient (7055).

Neurologic/CNS ...Orally, headache, fatigue, and insomnia (7076,7078,12207,13393,13395,15065), confusion (90617), and vertigo (7079) have been reported.

Other ...Orally, weight gain has been reported (12207,13393,15065).

(Read more about VITEX AGNUS-CASTUS)

General ...There is currently a limited amount of information on the adverse effects of ylang ylang oil. A thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Topically: Dermatitis, pruritus.

Dermatologic ...Topically, ylang ylang oil in combination with other herbs can cause localized pruritus (13483).

Immunologic ...Topically, ylang ylang oil in combination with other herbs has caused contact dermatitis in various case reports (98615).

(Read more about YLANG YLANG OIL)