Botanic Choice Bright Eye Blend by Indiana Botanic Gardens

There is insufficient reliable information available about the effectiveness of blackberry.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. Small clinical studies suggest that oral cardamom may slightly reduce glycated hemoglobin (HbA1c) in patients with type 2 diabetes, but it does not appear to improve blood glucose, blood pressure, or cholesterol levels in these patients. Details: A small clinical study in overweight or obese adults with type 2 diabetes who are taking antidiabetes medication shows that taking cardamom 1 gram three times daily for 10 weeks reduces HbA1c by 0.4% and improves insulin and triglyceride levels when compared with a rusk powder placebo (101887). However, other small clinical studies show that taking cardamom 1 gram three times daily does not reduce fasting blood glucose, blood pressure, or total cholesterol levels, or improve anthropometric measures in patients with type 2 diabetes (95597,99436,101887).
• Dyspepsia. Although there has been interest in using oral cardamom for dyspepsia, there is insufficient reliable information about the clinical effects of cardamom for this purpose.
• Epilepsy. Although there has been interest in using oral cardamom essential oil for epilepsy, there is insufficient reliable information about the clinical effects of cardamom for this purpose.
• Hyperlipidemia. Small clinical studies suggest that oral cardamom may modestly reduce triglyceride levels in patients with hyperlipidemia, but it does not seem to improve other lipid levels in these patients. Details: A meta-analysis of mostly small randomized controlled trials shows that taking cardamom 3 grams daily for 8-12 weeks does not improve total, low-density lipoprotein (LDL), or high-density lipoprotein (HDL) cholesterol levels. However, it might modestly reduce triglyceride levels when compared with placebo (101886).
• Hypertension. It is unclear if oral cardamom powder is beneficial in patients with hypertension. Details: A small clinical study in adults with newly-diagnosed, untreated, stage 1 essential hypertension shows that taking cardamom powder 1.5 grams orally twice daily for 12 weeks reduces systolic blood pressure by about 19 mmHg and diastolic blood pressure by about 12 mmHg when compared to baseline (95308). The validity of these findings is limited by the lack of a comparator group.
• Irritable bowel syndrome (IBS). Although there has been interest in using oral cardamom for IBS, there is insufficient reliable information about the clinical effects of cardamom for this purpose.
• Nausea and vomiting. Although there has been interest in using oral cardamom for nausea and vomiting, there is insufficient reliable information about the clinical effects of cardamom for this purpose.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral cardamom is beneficial in patients with NAFLD. Details: A small clinical study in overweight or obese patients with NAFLD shows that taking cardamom 1000 mg three times daily for 3 months improves some measures of cardiovascular and hepatic health when compared with placebo. Fatty liver grade, as measured by sonography, improved in 42% of patients taking cardamom, compared with 4.5% of those taking placebo. High-density lipoprotein (HDL) cholesterol levels, triglyceride levels, and insulin resistance also improved by a moderate amount. However, taking cardamom did not affect fasting blood glucose, body mass index (BMI), or low-density lipoprotein (LDL) cholesterol levels (101885).
• Obesity. It is unclear if oral cardamom is beneficial in patients with diabetes. Details: A small clinical study in overweight adults with diabetes shows that drinking black tea steeped with 3 grams of cardamom powder in three divided doses daily for 8 weeks does not affect weight, waist circumference, or blood pressure when compared with baseline or black tea only (95597).
• Polycystic ovary syndrome (PCOS). It is unclear if oral cardamom powder is beneficial in patients with PCOS. Details:A small clinical study in patients with PCOS shows that taking cardamom powder 1 gram three times daily for 16 weeks while following a low-calorie diet improves cyst size and number, reduces levels of testosterone and luteinizing hormone, increases levels of follicle stimulating hormone, and reduces levels of several inflammatory markers when compared with placebo plus a low-calorie diet (107920).
• Postoperative nausea and vomiting (PONV). Aromatherapy with cardamom essential oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study shows that applying a mixture of essential oils from ginger, cardamom, and tarragon topically to the neck at the first sign of PONV can inhibit nausea and/or vomiting for 30 minutes in 50% to 88% of postoperative patients. The treatment effect appears to vary depending on the number of emetic drugs given during anesthesia or postoperatively, and whether the drugs were given during or after the operation (77054). Another small study shows that aromatherapy with a mixture of ginger, spearmint, peppermint, and cardamom, as 3 inhalations from a gauze pad, reduces nausea scores by 43% when compared with placebo. When compared with ginger aromatherapy alone, nausea scores were reduced by 15%. Using the combination aromatherapy also reduced the need for anti-nausea medications by 40% when compared with placebo and by 15% when compared with ginger aromatherapy (95307). It is unclear if these benefits are due to cardamom, other ingredients, or the combination.
• Pregnancy-induced nausea and vomiting. Although there has been interest in using oral cardamom for pregnancy-induced nausea and vomiting, there is insufficient reliable information about the clinical effects of cardamom for this purpose.
• Respiratory tract infections. Although there has been interest in using oral cardamom for various respiratory tract infections, including bronchitis, influenza, and the common cold, there is insufficient reliable information about the clinical effects of cardamom for these conditions. More evidence is needed to rate cardamom for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Obesity. A small clinical study in overweight adults shows that taking a combination product containing damiana, guarana, and yerba mate for 45 days increases weight loss when compared with placebo (11866). It is not clear if this effect is due to damiana, other ingredients, or the combination.
• Sexual dysfunction. Preliminary clinical research shows that taking a specific combination product containing damiana, L-arginine, Panax ginseng, ginkgo, vitamins, and minerals (ArginMax for Women, Daily Wellness Co.) improves sexual satisfaction and desire, increases orgasm frequency, and reduces vaginal dryness when compared with placebo in women interested in improving their sexual function (46933). It is not clear if these effects are due to damiana, other ingredients, or the combination. More evidence is needed to rate damiana for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using topical eucalyptus for acne, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Asthma. A small clinical study suggests that taking the eucalyptol constituent of eucalyptus orally might have a steroid-sparing effect in some patients with asthma. Details: Preliminary clinical research in patients with steroid-dependent asthma shows that taking eucalyptol, a constituent of eucalyptus oil, 200 mg three times daily orally for 12 weeks, allows for an average reduction in prednisolone doses of 36%, compared with a 7% reduction in those taking placebo (13302).
• Bronchitis. Oral eucalyptol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some clinical research in patients with chronic bronchitis shows that taking a specific combination product containing eucalyptol and extracts of pine and lime (Myrtol standardized, MYS, Gelomyrtol forte) 900 mg daily orally for at least 1 month decreases the proportion of patients with acute exacerbations by 72%, compared with 53% for those taking placebo (48925). In patients with acute bronchitis, receiving the same product in a dose of 1200 mg daily for 14 days is associated with a reduction in symptoms in all but 1% of patients, compared with 32% of patients receiving placebo (48932).
• Burns. Although there is interest in using topical eucalyptus for burns, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Cancer. Although there is interest in using oral eucalyptus for cancer, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Chronic obstructive pulmonary disease (COPD). A small clinical study suggests that the eucalyptol constituent of eucalyptus might reduce acute exacerbations in patients with stable COPD. Details: Clinical research in adults with stable, moderate to severe COPD shows that adding eucalyptol, 200 mg three times daily, to conventional therapy for 6 months, including the winter season, reduces the proportion of patients experiencing acute exacerbations from 46% to 28% when compared with placebo (104960).
• Cough. Oral eucalyptus oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of four clinical studies in patients with cough associated with bronchitis or upper respiratory tract infection shows that taking eucalyptus oil, either in combination with pine and lime essential oils (Myrtol or Gelomyrtol) or with Origanum syriacum, peppermint, and rosemary essential oils, daily for up to 6 months increases the likelihood of improvement or resolution of cough symptoms by 45% when compared with placebo (110095).
• Dental plaque. Using chewing gum containing eucalyptus extract might reduce dental plaque. Details: Preliminary clinical research shows that chewing gum containing 0.3% to 0.6% eucalyptus extract 3-5 times daily for 4 days to 12 weeks reduces dental plaque when compared with placebo (49010,92863).
• Diabetes. Although there is interest in using oral eucalyptus for diabetes, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Endotracheal intubation-associated adverse effects. It is unclear if nebulized eucalyptus oil is beneficial for prevention of complications associated with endotracheal intubation. Details: A small clinical study in Iranian patients intubated and receiving care in the intensive care unit shows that nebulizing 4 mL of eucalyptus 5% oil in 6 mL of normal saline every 8 hours for 3 days increases oxygen saturation and decreases peak inspiratory pressure, but does not affect the level of consciousness as measured using the Glasgow Coma Scale, when compared with nebulized normal saline (110096).
• Genital herpes. Although there is interest in using topical eucalyptus for genital herpes, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Gingivitis. Using chewing gum containing eucalyptus extract might improve gingivitis. Details: Preliminary clinical research shows that chewing gum containing 0.4% to 0.6% eucalyptus extract five times daily for 4 days improves gingivitis when compared with placebo (92863).
• Gonorrhea. Although there is interest in using oral eucalyptus for gonorrhea, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Halitosis. Using chewing gum containing eucalyptus extract might improve halitosis. Details: Preliminary clinical research shows that chewing gum containing 0.4% to 0.6% eucalyptus extract five times daily for 12 weeks significantly improves halitosis and coating of the tongue when compared with placebo (92863).
• Headache. Topical eucalyptus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a combination of peppermint oil, eucalyptus oil, and ethanol topically to the forehead and temples does not affect headache pain, but improves cognitive performance and produces relaxation, when compared with placebo (3801).
• Influenza. Although there is interest in using oral or inhaled eucalyptus for influenza, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Lice. Topical eucalyptus oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with head lice shows that applying eucalyptus oil 11% and lemon tea tree oil 1% (MOOV Head Lice Solution, Ego Pharmaceuticals Pty Ltd.) reduces the ex-vivo egg hatching rate by only 3%, compared with a 44% reduction with tea tree oil and lavender oil (NeutraLice Natural Lotion), and a 68% reduction with benzyl alcohol, mineral oil, and triethanolamine (NeutraLice Advance) (19188). However, other research in elementary school aged children shows that applying the MOOV Head Lice Solution combination product to the scalp for 10 minutes, once weekly for 3 weeks, is more effective than applying pyrethrins and piperonyl butoxide once weekly for 2 weeks. At 7 days after the last application, 71% of children treated with the eucalyptus formulation were still free of lice, compared with 33% of children in the control group (98492).
• Onychomycosis. Although there is interest in using topical eucalyptus for onychomycosis, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Oral mucositis. Although there is interest in using topical or oral eucalyptus for oral mucositis, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Osteoarthritis. Although there is interest in using topical eucalyptus for osteoarthritis, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Rheumatoid arthritis (RA). It is unclear if inhaled eucalyptus oil is beneficial in patients with RA. Details: A small clinical study in patients with RA shows that aromatherapy with eucalyptus essential oil, delivered by applying 2 mL of oil to pads attached to clothing for 5 minutes three times daily for 1 month, reduces pain and improves quality of life when compared with placebo (110094).
• Rhinosinusitis. Although there is interest in using inhaled eucalyptus for rhinosinusitis, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Tinea corporis. Although there is interest in using topical eucalyptus for tinea corporis, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Tuberculosis. Although there is interest in using oral eucalyptus for tuberculosis, there is insufficient reliable information about the clinical effects of eucalyptus for this condition.
• Ventilator-associated pneumonia (VAP). It is unclear if eucalyptus is beneficial for the prevention of VAP. Details: Preliminary clinical research in ventilated adult patients shows that nebulizing a 2% eucalyptus solution for about 20 minutes every 8 hours reduces the incidence of late bacterial pneumonia (occurring more than 96 hours after initiation of ventilation) from 58% to 30% when compared with placebo. In those patients who developed VAP, the onset occurred approximately 3 days later, on average, in the eucalyptus group than in the placebo group (104958).
• Wound healing. Although there is interest in using topical eucalyptus for wound healing, there is insufficient reliable information about the clinical effects of eucalyptus for this condition. More evidence is needed to rate eucalyptus for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Conjunctivitis. Preliminary clinical research shows that applying one drop of eyebright eye drops (WALA Heilmittel GmbH, Eck-walden/Bad Boll) up to five times daily results in complete recovery in about 82% of patients with conjunctivitis after two weeks of treatment (49391). However, due to the lack of a comparator group, it is not clear if this improvement is due to eyebright or to the natural resolution of conjunctivitis symptoms. More evidence is needed to rate eyebright for this use.

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There is insufficient reliable information available about the effectiveness of linden.

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LIKELY EFFECTIVE

• Irritable bowel syndrome (IBS). Oral enteric-coated peppermint oil is conditionally recommended by the American College of Gastroenterology (ACG) for the relief of global IBS symptoms, such as abdominal pain. Details: The ACG conditionally recommends the use of peppermint for the relief of global IBS symptoms. This recommendation is based on an available meta-analysis of generally low-quality clinical research (105124). Several clinical trials and meta-analyses show that taking enteric-coated peppermint oil 1-2 capsules orally two to four times daily reduces abdominal pain, distention, flatulence, and bowel movements in patients with IBS. Each capsule provides approximately 0.2 mL of peppermint oil or 180-225 mg peppermint oil. Most trials have used specific products (Colpermin, Tillotts Pharma; Mintoil, Cadigroup; Ibgard, IM HealthScience, Tempocol) (3802,3803,4469,11778,11779,17681,17682,68467,68515,68522)(68603,68604,68605,96360,99493,109980). The most recent meta-analysis to date shows that four patients would need to take peppermint oil to prevent one patient from having persistent IBS symptoms, and seven patients would need to take peppermint oil to prevent one patient from having abdominal pain. However, the individual studies included in the analysis lasted no more than 12 weeks (109980); any long-term effects are unclear. Although most studies have shown benefit for reducing symptoms, some older studies have found no significant effect (11777,11789) or only short-term benefits (68620). Also, a well-designed study shows that taking peppermint oil capsules designed for either small intestinal release (enteric-coated) or ileocolonic release does not increase the number of people with at least a 30% decrease in abdominal pain over a period of 4 weeks, although symptoms are modestly reduced when compared with placebo (102602). Another clinical trial in patients with moderate to severe IBS shows that taking a specific enteric-coated formulation of peppermint oil (Pepogest; Nature's Way) 180 mg three times daily for 6 weeks does not further improve symptom severity when compared with placebo. However, both groups experienced a large improvement on the IBS-Severity Scoring System (IBS-SSS) and the IBS Global Improvement Scale (107955). The validity of these findings is limited due to lost data and inconsistent follow-up; additionally, adverse effects occurred more frequently in the peppermint oil group. The reasons for these negative findings are unclear but may include short treatment durations and the use of different formulations; additionally, IBS is comprised of various subtypes and symptoms that can range in severity and presentation, which may alter treatment response. Some clinical research has also evaluated a specific combination product (Atrantil, KBS Research) containing peppermint leaf, red quebracho extract, and conker tree extract. Taking this product as needed for 2 weeks seems to reduce constipation and bloating when compared to baseline in patients with constipation-predominant IBS (95429,95430). It is unclear if the effects of this product are due to peppermint, the other ingredients, or the combination.

POSSIBLY EFFECTIVE

• Barium enema-related colonic spasm. Rectal peppermint, as part of barium enema preparations, seems to reduce colonic spasms during examination. Oral peppermint also seems to be beneficial. Details: Rectal use of peppermint oil, added as an ingredient in barium enema preparations, seems to relax the colon during barium enema examination and reduce the percentage of patients who experience colonic spasms by about 25% to 30% (6739,6749,12009). Adding peppermint oil to the barium enema seems to be at least as effective as using systemic scopolamine (Buscopan). Adding peppermint oil to the barium solution also does not seem to impair image quality (12009). Some clinical research also shows that taking peppermint oil orally before the start of a double-contrast barium enema examination decreases spasms and might also increase diagnostic quality (14467).
• Chemotherapy-induced nausea and vomiting (CINV). Oral and inhaled peppermint seem to reduce nausea and vomiting in patients with CINV. Details: Clinical research shows that adding peppermint oil, 40 drops in 20 mL water, every 8 hours following chemotherapy treatment to treatment with standard antiemetics reduces the severity of nausea, vomiting, and anorexia by moderate to large amounts over 48 hours when compared with a plain water placebo (105123). The use of peppermint oil aromatherapy has also been investigated. Clinical research shows that adding 2 drops of peppermint oil to a cool, damp washcloth for use on the neck as aromatherapy for about 30 minutes helps relieve chemotherapy-induced nausea by a small amount when compared with a washcloth without peppermint oil (102603). Additional clinical research in patients receiving standard antiemetics after chemotherapy shows that applying one drop of peppermint oil below the nose three times daily for 5 days reduces the severity of nausea and the frequency of nausea, vomiting, and retching by a moderate to large amount when compared with the antiemetics alone. These parameters were not improved following treatment with cisplatin (105122). In children with acute leukemia, a small clinical study shows that aromatherapy with 2 drops of peppermint oil and 3 drops of lemon oil in 80 mL of water diffused 30 minutes prior to and 2 and 4 hours after chemotherapy once weekly for 4 weeks decreases the severity of nausea, vomiting, and retching, and improves quality of life scores when compared with diffused water or no intervention (112015). The validity of these findings is limited by the use of patient-reported outcomes.
• Dyspepsia. Oral peppermint, in combination with caraway and possibly other ingredients, seems to reduce symptoms of dyspepsia. It is unclear if oral peppermint alone is beneficial. Details: Some clinical research shows that taking specific products containing peppermint and caraway oil (Enteroplant, Dr Willmar Schwabe Pharmaceuticals; Menthacarin, Dr Willmar Schwabe GmbH & Co.) improves quality of life and reduces symptoms of dyspepsia, including feelings of fullness, pain, and mild gastrointestinal spasms (6740,6741,10075,96344,102600). A meta-analysis of three of these clinical studies shows that taking this combination product 2-3 times daily for 4 weeks modestly reduces abdominal pain when compared with placebo (110091). Taking this combination twice daily for 4 weeks also improves postprandial distress syndrome and epigastric pain syndrome, two subtypes of dyspepsia, when compared with placebo (96344). The combination of enteric-coated peppermint oil 90 mg and caraway oil 50 mg appears to be comparable to cisapride for relieving dyspepsia when taken 2-3 times daily for up to 4 weeks (6740,6741,10075). However, most trials investigating this combination are small and/or of overall low quality (102600). A specific combination product containing peppermint leaf (Iberogast, Steigerwald Arzneimittelwerk GmbH) also seems to improve symptoms of dyspepsia. The combination includes peppermint leaf plus clown's mustard plant, German chamomile, caraway, licorice, milk thistle, angelica, celandine, and lemon balm (7049). A meta-analysis of studies using this combination product shows that taking 1 mL orally three times daily over a period of 4 weeks reduces the severity of acid reflux, epigastric pain, cramping, nausea, and vomiting when compared with placebo (13089). A similar combination product containing extracts from peppermint leaf, clown's mustard plant, German chamomile flower, caraway, licorice root, and lemon balm (STW 5-II, Steigerwald Arzneimittelwerk GmbH) 1 mL taken three times daily for up to 8 weeks eliminates gastrointestinal symptoms in 40% more dyspepsia patients when compared with placebo (12724).
• Endoscopy-associated adverse effects. Intraluminal peppermint seems to reduce spasticity during an endoscopy. It is unclear if oral peppermint is beneficial for reducing adverse effects related to endoscopy. Details: A meta-analysis of four clinical trials show that peppermint oil, administered orally or intraluminally, reduces the incidence of spasticity by about 41% when compared with placebo in patients undergoing endoscopy, with severe spasticity occurring at about 30% the rate of those taking placebo. However, there was no effect on subjective pain (102604). Individual clinical studies show that intraluminal peppermint oil can reduce both pain and spams in patients undergoing endoscopy (18220,68371,68395,68445,68532). However, there are limitations with this form of administration, including cost and practicality, which has led to interest in the use of oral formulations (104221). Studies evaluating oral extended-release peppermint have been conflicting. While one study shows that a specific extended-release peppermint oil product (Colpermin) 187 mg or 0.2 mL taken orally 4 hours prior to a colonoscopy reduces procedure time, pain, and spasticity (68532), a study using another specific extended-release peppermint oil (IBGard) did not show an effect on colonic spasms, procedure time, or adenoma detection rate when compared with placebo (104221). These differing outcomes may be due to timing of administration. The study that showed benefit administered the treatment 4 hours prior to endoscopy, whereas the study showing no benefit administered the treatment only 1 hour prior. This suggests that extended-release peppermint may need to be administered at least 4 hours prior to the procedure to allow for adequate colonic release (68532,102604,104221).
• Nipple fissures. Topical peppermint seems to reduce cracked skin and pain in the nipples due to breastfeeding. Details: Clinical research shows that topical application of peppermint oil in gel or water reduces cracked skin and pain in the nipple area from breastfeeding when compared with using placebo, lanolin, or the expressed breast milk technique (68454,68462). Other research shows that applying peppermint oil in cream immediately after breastfeeding for 2 weeks decreases pain and trauma in the nipple area similarly to the topical application of dexpanthenol or lanolin (96365).
• Pressure ulcers. Topical peppermint seems to reduce the risk of pressure ulcers. Details: Clinical research in bedridden patients shows that prophylactic application of a topical gel containing peppermint oil 0.2% three times daily for up to 14 days results in pressure injuries in about 23% of patients compared with 77% of those given a placebo gel (102605).
• Tension headache. Topical peppermint seems to relieve tension headaches. Details: Clinical research shows that topical application of peppermint oil 10% relieves tension headaches when compared with placebo (3801,6190).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abdominal pain. Although there has been interest in using oral peppermint for abdominal pain, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Anxiety. It is unclear if inhaled peppermint oil is beneficial for reducing anxiety. Details: A clinical trial in patients presenting to the emergency department for an acute coronary syndrome event shows that placing 3 drops of peppermint oil on a cotton ball and inhaling for 1 hour improves anxiety and respiratory rate when compared with baseline or placebo (107958). Due to the single-dose nature of this study, the effects of repeated inhalation of peppermint oil are unclear.
• Breast cancer-related hot flashes. It is unclear if topical peppermint is beneficial for reducing hot flashes in patients with breast cancer. Details: Preliminary clinical research shows that using a spray containing a combination of peppermint and neroli hydrolat does not alleviate hot flashes in most patients receiving chemotherapy for breast cancer when compared with using a plain water spray (68481).
• Cognitive function. It is unclear if inhaled peppermint oil is beneficial for improving cognitive function. Details: Preliminary clinical research shows that inhalation of peppermint oil slightly improves memory and the performance of cognitive tasks such as typing, alphabetization, and ordering, but not attention and speed of task completion, when compared with control (56954,68416,68466).
• Common cold. Although there has been interest in using oral, topical, or inhaled peppermint for the common cold, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Dental plaque. Topical peppermint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that rinsing the mouth for one minute with 10 mL of a specific combination product (HiOra, Himalaya Herbal Healthcare) containing peppermint oil and numerous other ingredients twice daily for two days reduces plaque index or plaque area when compared with placebo; however, it was not as effective as chlorhexidine 0.2% solution (68530). It is unclear if these effects are due to peppermint oil, other ingredients, or the combination.
• Diffuse esophageal spasm. It is unclear if oral peppermint oil is beneficial for diffuse esophageal spasm. Details: A small exploratory study in adults with diffuse esophageal spasm shows that drinking a solution of peppermint oil, 5 drops in 10 mL of water, can resolve esophageal contractions when compared with baseline (13415). The validity of this finding is limited by the lack of a comparator group.
• Dysmenorrhea. It is unclear if oral peppermint oil is beneficial for reducing menstrual pain. Details: Preliminary clinical research shows that taking three capsules of peppermint oil (Colpermin; Tillotts Company or Razak company) daily for 3 days, starting on the first day of menstruation, is as effective as mefenamic acid 250 mg three times daily for reducing pain, and more effective for reducing nausea and vomiting, associated with dysmenorrhea. However, mefenamic acid was more effective for reducing bleeding and analgesic use (105125).
• Fatigue. It is unclear if inhaled peppermint oil improves fatigue in patients with cardiac disease. Details: A clinical trial in hospitalized patients with various forms of cardiac disease shows that placing 3 drops of peppermint oil on a cotton ball and inhaling for 20 minutes nightly for 7 days improves fatigue scores when compared with placebo. These improvements were similar to those seen with lavender oil inhalation. Fatigue scores decreased by 24 and 21 points in the peppermint and lavender groups, respectively, compared with a 2-point reduction in the placebo group (107959). The validity of these findings is limited due to the short duration of treatment.
• Halitosis. Peppermint has only been evaluated in combination with other ingredients as a mouthwash; its effect when used alone is unclear. Details: Preliminary clinical research shows that rinsing the mouth with a specific combination of tea tree oil, peppermint, and lemon essential oil once for three minutes improves breath smell when compared with placebo or benzydamine hydrochloride (19177).
• Insomnia. It is unclear if inhaled peppermint oil is beneficial for insomnia. Details: Preliminary clinical research in cancer patients shows that receiving aromatherapy as three drops of peppermint oil applied to a cotton ball and attached to the collar for 20 minutes at bedtime for one week improves sleep when compared with baseline. However, it seems to be no better than using lavender oil aromatherapy or using a control of lavender oil 1% (103063).
• Menopausal symptoms. Although there has been interest in using inhaled peppermint oil for menopausal symptoms, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Migraine headache. It is unclear if intranasal peppermint oil is beneficial for migraine headache. Details: Preliminary clinical research shows that using 1-2 doses of intranasal peppermint oil 1.5% (Poursina Company) at the start of migraine pain is as effective as intranasal lidocaine 4%, and more effective than placebo, for reducing migraine headache intensity. Approximately 42% of those using peppermint oil indicated a high level of headache reduction, compared with 42% of those using lidocaine and 5% of those using placebo. Also, pain relief was felt within 5 minutes in more patients using peppermint than placebo (105126). However, it is unclear if participants were truly blinded to the use of peppermint oil.
• Mosquito repellent. Although there has been interest in using topical peppermint oil as a mosquito repellent, there is insufficient reliable information about the clinical effects of peppermint for this purpose.
• Myalgia. Although there has been interest in using topical peppermint oil for myalgia, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Oral mucositis. Topical peppermint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults undergoing stem cell transplantation shows that using an oral rinse containing peppermint oil and German chamomile three times daily, in addition to standard treatment with sodium chloride and chlorhexidine, reduces the duration and severity of mucositis and the use of narcotic analgesics when compared with placebo and standard treatment. However, this oral rinse does not reduce or delay the occurrence of mucositis or affect the duration of hospitalization (96363). Another small clinical study in adults with head and neck cancers undergoing radiation shows that rinsing with 5 mL of a polyherbal mouthwash containing peppermint oil, German chamomile, aloe vera, and honey for 1 minute 3 times daily for 6 weeks reduces oral mucositis incidence, severity, and pain when compared with chlorhexidine 0.2% and placebo (111291). Clinical research in adults receiving treatment with 5-fluorouracil shows that using an oral rinse containing peppermint, sage tea, and thyme in addition to basic oral care, starting on the first day of chemotherapy and continuing for 14 days, delays the onset of mucositis, but not the rate or severity of mucositis, when compared with basic oral care alone (96364). It is unclear if these effects are due to peppermint oil, other ingredients, or the combinations.
• Osteoarthritis. Although there has been interest in using topical peppermint oil for osteoarthritis, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Pain (acute). It is unclear if inhaled peppermint oil is beneficial for acute pain. Details: Preliminary clinical research in cardiac patients shows that peppermint oil aromatherapy reduces pain associated with intravenous catheterization by a small amount when compared with a distilled water control (102601).
• Postherpetic neuralgia. Although there has been interest in using topical peppermint oil for postherpetic neuralgia, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Postoperative ileus. It is unclear if oral peppermint oil is beneficial for the prevention of postoperative ileus. Details: Clinical research shows that taking a specific peppermint oil product (Colpermin, Tillotts Pharma) as two capsules three times daily for 5 days after routine gynecological surgery does not prevent postoperative abdominal distension and dyspepsia when compared with placebo (68602). Conversely, a small clinical study in patients undergoing elective cesarean section shows that taking 20 drops of peppermint oil 4 hours after surgery and then hourly for a total of three doses reduces the time to first bowel sounds by around 3.3 hours, first flatulence by 4.4 hours, and first stool by 5 hours when compared with placebo (110092).
• Postoperative nausea and vomiting (PONV). Some preliminary clinical studies suggest that inhaled peppermint may be beneficial for PONV. However, it is unclear if the benefit is due to aromatherapy or improved breathing patterns. Details: Some preliminary clinical research shows that using peppermint aromatherapy helps relieve postoperative nausea (3804,13415,68524,104219,104220). Inhaling peppermint oil 10% and 30% as aromatherapy reduces the severity of nausea when compared with placebo, with no significant difference between concentrations (104220). Small clinical trials show improvement in PONV within the first 4 hours after surgery. However, this effect diminishes beyond 4 hours (104219). Other preliminary clinical research shows that peppermint oil aromatherapy is no more effective for reducing postoperative nausea than inhaling isopropyl alcohol or saline (13416,68529). It is possible that any relief of postoperative nausea observed with peppermint aromatherapy results from improved breathing patterns after surgery rather than peppermint oil itself (13416,90512). One small study shows that inhaling peppermint oil while practicing controlled breathing does not appear to relieve PONV better than practicing controlled breathing alone (90512). Some preliminary clinical research shows that inhaling vapors from a mixture of peppermint, ginger, spearmint, and cardamom essential oils reduces symptoms of postoperative nausea in approximately 15% more patients when compared with inhaling ginger essential oils alone, and in approximately 43% more patients when compared with inhaling saline (89888). However, it is not clear if the effect is due to peppermint, the other oils, or the combination.
• Pre-procedural anxiety. It is unclear if inhaled peppermint oil is beneficial for reducing anxiety prior to a medical procedure. Details: Preliminary clinical research in cardiac patients shows that peppermint oil aromatherapy does not reduce anxiety associated with intravenous catheterization when compared with a distilled water control (102601).
• Pregnancy-induced nausea and vomiting. Inhaled peppermint oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that aromatherapy with a mixture of 5% lemon and 5% peppermint essential oils modestly reduces the intensity of nausea and vomiting on days 2-4, but not day 1, when compared with placebo aromatherapy. When nauseated, patients placed three drops of the essential oil mixture (Barij Essence Co.) onto a cotton ball held 3 cm from the nose. This action could be repeated after 5 minutes if needed (105121).
• Pruritus. Some preliminary clinical studies suggest that topical peppermint oil improves itching of various etiologies. Details: Preliminary clinical research in adults with renal, hepatic, or diabetic pruritus shows that topical application of peppermint oil 5% in petrolatum twice daily for 2 weeks improves symptoms of pruritus when compared with petrolatum alone (96361). Preliminary clinical research in patients with severe or intractable pruritus secondary to burn scars shows that applying a specific product (Chongqing No.1, CQ-01, MJ Medical Gel Systems Ltd.) containing peppermint oil 3.6%, menthol 1.4%, and methyl salicylate 2.5%, covered with gauze for 24 hours, reduces the severity of pruritus for up to 7 days after application when compared with hydrogel covered with gauze or with gauze alone (96362). Preliminary clinical research in females experiencing itchy skin due to intrahepatic cholestasis of pregnancy also shows that applying peppermint oil 0.5% in sesame oil twice daily for 2 weeks reduces pruritus severity approximately 1.8-fold when compared with sesame oil alone (89478).
• Small intestinal bacterial overgrowth (SIBO). Although there has been interest in using oral peppermint for SIBO, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Stress. It is unclear if inhaled peppermint oil is beneficial for stress. Details: Clinical research shows that peppermint aromatherapy decreases physical and perceived levels of stress when compared with baseline (68422,68517). A small clinical study in adults undergoing a virtual reality (VR) driving scenario to test road rage shows that exposure to peppermint oil (Pure Essential Oil of Peppermint, Tisserand Aromatherapy) 5 drops via fan diffuser improves aggressive driving behavior scores but does not seem to improve self-reported stress, aggression, alertness, happiness, or calmness when compared with controls that did not receive aromatherapy during the VR session (112017).
• Toothache. Although there has been interest in using topical peppermint oil for toothache, there is insufficient reliable information about the clinical effects of peppermint for this condition.
• Urticaria. Although there has been interest in using topical peppermint oil for urticaria, there is insufficient reliable information about the clinical effects of peppermint for this condition. More evidence is needed to rate peppermint for these uses.

(Read more about PEPPERMINT)

LIKELY EFFECTIVE

• Cystic fibrosis. Long-term nebulized hypertonic sodium chloride improves lung function and reduces pulmonary exacerbations in patients with cystic fibrosis. Details: Meta-analyses of clinical research in adults with cystic fibrosis show that, when taken along with a bronchodilator and other standard therapies, nebulized hypertonic sodium chloride in concentrations of 3% to 7%, up to 10 mL twice daily for 4 weeks, increases forced expiratory volume at one second (FEV1) when compared with isotonic saline (sodium chloride 0.9%) (26230,26230). This benefit was not seen at 48 weeks. Other clinical research in adults with cystic fibrosis shows that inhaling sodium chloride 7%, 4 mL twice daily for 48 weeks, does not improve FEV1 when compared with isotonic saline. However, chronic treatment with hypertonic saline does reduce the number of pulmonary exacerbations and increase the number of patients without pulmonary exacerbations when compared with isotonic saline (29402). It is not clear if this benefit occurs in children with cystic fibrosis. The Pulmonary Clinical Practice Guidelines Committee of the Cystic Fibrosis Foundation recommends that individuals with cystic fibrosis aged 6 years or older use nebulized hypertonic saline long-term to improve lung function, reduce the number of exacerbations, and improve quality of life (29403).

POSSIBLY EFFECTIVE

• Amphotericin B nephrotoxicity. Oral sodium chloride seems to prevent nephrotoxicity associated with use of amphotericin B. Details: Clinical research shows that administering oral or intravenous sodium chloride 150 mEq daily during treatment with amphotericin B can attenuate the rise in serum creatinine levels and preserve renal function when compared to treatment with amphotericin B alone (26226).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bipolar disorder. It is unclear if oral sodium is beneficial in preventing lithium level fluctuations in patients with bipolar disorder. Details: A moderate-sized open-label clinical study in adults with type I bipolar disorder receiving lithium carbonate shows that taking sodium chloride 1 gram daily for 12 weeks along with dietary salt restriction of 1 gram daily reduces the percentage of patients with lithium level fluctuations above 0.8 mEq/L, but does not significantly affect serum sodium, potassium, aldosterone, or creatinine levels when compared with controls who were not salt restricted, but were advised not to consume additional salt at the table (112909). However, the interpretation of these findings is limited by missing data in both groups.
• Canker sores. Although there is interest in using topical sodium chloride for canker sores, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Congestive heart failure. It is unclear if oral sodium is beneficial in patients with acute decompensated heart failure requiring decongestive therapy with diuretics. Details: A moderate-sized clinical study in adults hospitalized with acute decompensated heart failure requiring high-dose intravenous furosemide shows that taking sodium chloride 2 grams three times daily for up to 96 hours does not affect patient weight or serum creatinine levels when compared with placebo (112911). However, the clinical relevance of this study is unclear and it may have been inadequately powered to detect a difference between groups.
• Conjunctivitis. Although there is interest in using ophthalmic sodium chloride for conjunctivitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Hyponatremia. Although there is interest in using oral sodium chloride for hyponatremia, there is insufficient reliable information about the clinical effects of oral sodium chloride for this condition.
• Pharyngitis. Although there is interest in using topical sodium chloride for pharyngitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Prematurity. It is unclear if oral sodium is beneficial for premature infants. Details: Preliminary clinical research in infants born at less than 32 weeks' gestation shows that adding sodium 4 mEq/kg daily to enteral feedings, starting from the 7th day after birth and continuing through the 35th day, reduces the risk of developing hyponatremia and improves weight gain when compared with adding water (98180). A small, open-label clinical study in newborns less than 35 weeks gestation shows that high sodium intake, defined as an average of 0.25% sodium in maintenance fluids, for 48 hours on day 2 and 3 after birth results in less weight loss within the first 72 hours of life when compared with control, but does not improve mortality, length of hospital stay, or complications from prematurity (112908). However, interpretation of these findings is limited by varied concentrations of sodium as an intervention. More evidence is needed to rate sodium for these uses.

(Read more about SODIUM)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral spearmint extract is beneficial for age-related cognitive decline. Details: A small clinical study in older adults with age-related cognitive decline shows that taking a specific spearmint extract 900 mg daily for 90 days modestly improves quality of working memory, as well as time to sleep, overall mood, and feelings of vigor, when compared with placebo. However, no improvements were seen in attention, overall quality of memory, speed of memory, quality of sleep, or feelings of anxiety, depression, or confusion. Additionally, taking 600 mg daily does not seem to provide benefit (98523).
• Cognitive function. Small clinical studies suggest that oral spearmint extract or spearmint-flavored gum may not improve most measures of cognitive function. Details: One small clinical study in healthy young adults shows that taking a proprietary spearmint extract (Neumentix Phenolic Complex K110-42, Kemin Foods, LC.) 900 mg daily for 90 days modestly improves attention, but not working memory, executive function, speed, reasoning, or other measures of cognitive function, when compared with placebo (101713). Other small clinical studies in healthy adults shows that chewing spearmint-flavored gum during memory testing does not improve memory or attention when compared with chewing unflavored gum (75725,75754).
• Flatulence. Although there has been interest in using oral spearmint for flatulence, there is insufficient reliable information about the clinical effects of spearmint for this purpose.
• Hirsutism. Small clinical studies suggest that drinking spearmint tea may modestly reduce testosterone levels in patients with hirsutism; any effects on hair growth are unclear. Details: A small clinical study in patients with hirsutism associated with polycystic ovary syndrome (PCOS) shows that drinking spearmint tea twice daily for one month can reduce the subjective severity of hirsutism when compared to pretreatment; however, it does not seem to reduce the amount or location of hair based on objective assessment when compared with placebo tea (68500). Any effect of spearmint tea in patients with hirsutism is believed to be related to its antiandrogenic properties. Two small clinical studies in patients with idiopathic hirsutism or hirsutism associated with PCOS show that drinking spearmint tea twice daily for 5-30 days can decrease free testosterone levels and increase levels of luteinizing hormone, estradiol, and follicle-stimulating hormone when compared to baseline (68451,68500).
• Irritable bowel syndrome (IBS). Oral spearmint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with IBS shows that using 30 drops of a combination product containing lemon balm, spearmint, and coriander (Carmint) three times daily after meals for 8 weeks along with conventional therapy with loperamide or psyllium reduces abdominal pain and discomfort by approximately 81% when compared with conventional therapy alone (19535). It is unclear if these findings are due to spearmint, other ingredients, or the combination.
• Osteoarthritis. It is unclear if drinking spearmint tea is beneficial in patients with knee osteoarthritis. Details: A small clinical study in patients with knee osteoarthritis shows that drinking 2 cups of spearmint tea daily for 16 weeks reduces pain and stiffness when compared to baseline (94923). The validity of these findings is limited by a lack of control group.
• Postoperative nausea and vomiting (PONV). Aromatherapy with spearmint oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in patients reporting nausea after surgery shows that inhaling vapors from a mixture of spearmint, peppermint, ginger, and cardamom essential oils reduces symptoms of postoperative nausea in approximately 15% more patients when compared with inhaling ginger essential oils alone, and in about 43% more patients when compared with inhaling saline (89888). It is unclear if these findings are due to spearmint oil, other ingredients, or the combination. More evidence is needed to rate spearmint for these uses.

(Read more about SPEARMINT)

LIKELY SAFE ...when the fruit is used orally in amounts commonly found in foods (4912). There is insufficient reliable information available about the safety of blackberry fruit or leaf when used in medicinal amounts.

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

(Read more about BLACKBERRY)

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

POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. Cardamom powder 3 grams daily in 2-3 divided doses has been used with apparent safety for up to 16 weeks (95308,95597,101885,107920). ...when the essential oil is used by inhalation for aromatherapy (77054,95307).

PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods.

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Cardamom is thought to have abortifacient and emmenagogue effects (19,39884). Avoid using amounts greater than those used in food.

LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods. There is insufficient reliable information available about the safety of cardamom when used in medicinal amounts. Avoid using amounts greater than those used in food.

(Read more about CARDAMOM)

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

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12,46933,11866).

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

(Read more about DAMIANA)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Eucalyptus has Generally Recognized As Safe status (GRAS) for use in foods as a flavoring in the US (4912).

POSSIBLY SAFE ...when eucalyptol, a constituent of eucalyptus oil, is used orally and appropriately. Eucalyptol appears to be safe for up to 12 weeks (13302).

POSSIBLY UNSAFE ...when the undiluted oil is used topically. Prolonged or widespread exposure has caused neurotoxicity (12869). There is insufficient reliable information available about the safety of diluted eucalyptus oil when used topically.

LIKELY UNSAFE ...when the undiluted oil is ingested orally. Ingesting 3.5 mL of undiluted oil can be fatal in adults (12867). There is insufficient reliable information available about the safety of eucalyptus oil when inhaled as aromatherapy or when eucalyptus leaf is used orally in medicinal amounts.

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

CHILDREN: LIKELY UNSAFE
when eucalyptus oil is used orally (12867,49002,107493,107495). ...when eucalyptus oil is used topically in infants and young children. There are reports of neurotoxicity in infants and young children exposed to topical eucalyptus oil. In one of these cases, a 12-month-old child was bathed in water containing eucalyptus oil and other essential oils; in another case, a child had a dressing containing eucalyptus oil applied every 2-4 hours daily for 2 days (12868,12869). ...when eucalyptus solutions are inhaled using a vaporizer (49002).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (4912). There is insufficient reliable information available about the safety of medicinal amounts of eucalyptus oil; avoid using.

(Read more about EUCALYPTUS)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Eyebright is listed by the Council of Europe as a natural source of food flavoring (4).

POSSIBLY UNSAFE ...when applied into the eyes. Avoid using due to hygienic concerns; eyebright ophthalmic products may be subject to contamination (8,11). There is insufficient reliable information available about the safety of eyebright when used orally in medicinal amounts.

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

(Read more about EYEBRIGHT)

LIKELY SAFE ...when linden leaf is used orally and appropriately in amounts normally found in foods (12). Linden leaf has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of linden when used orally or topically in medicinal amounts.

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

(Read more about LINDEN)

LIKELY SAFE ...when peppermint oil is used orally, topically, or rectally in medicinal doses. Peppermint oil has been safely used in multiple clinical trials (3801,3804,6190,6740,6741,10075,12009,13413,14467,17681)(17682,68522,96344,96360,96361,96362,96363,96364,96365,99493).

POSSIBLY SAFE ...when peppermint leaf is used orally and appropriately, short-term. There is some clinical research showing that peppermint leaf can be used safely for up to 8 weeks (12724,13413). The long-term safety of peppermint leaf in medicinal doses is unknown. ...when peppermint oil is used by inhalation as aromatherapy (7107). There is insufficient reliable information available about the safety of using intranasal peppermint oil.

CHILDREN: POSSIBLY SAFE
when used orally for medicinal purposes. Enteric-coated peppermint oil capsules have been used with apparent safety under medical supervision in children 8 years of age and older (4469).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (96361). There is insufficient information available about the safety of using peppermint in medicinal amounts during pregnancy or lactation; avoid using.

(Read more about PEPPERMINT)

LIKELY SAFE ...when used orally and appropriately. Sodium is safe in amounts that do not exceed the Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams daily (100310). Higher doses can be safely used therapeutically with appropriate medical monitoring (26226,26227).

POSSIBLY UNSAFE ...when used orally in high doses. Tell patients to avoid exceeding the CDRR intake level of 2.3 grams daily (100310). Higher intake can cause hypertension and increase the risk of cardiovascular disease (26229,98176,98177,98178,98181,98183,98184,100310,109395,109396,109398,109399). There is insufficient reliable information available about the safety of sodium when used topically.

CHILDREN: LIKELY SAFE
when used orally and appropriately (26229,100310). Sodium is safe in amounts that do not exceed the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310).

CHILDREN: POSSIBLY UNSAFE
when used orally in high doses. Tell patients to avoid prolonged use of doses exceeding the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310). Higher intake can cause hypertension (26229).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Sodium is safe in amounts that do not exceed the CDRR intake level of 2.3 grams daily (100310).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in higher doses. Higher intake can cause hypertension (100310). Also, both the highest and the lowest pre-pregnancy sodium quintile intakes are associated with an increased risk of hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, and the delivery of small for gestational age (SGA) infants when compared to the middle intake quintile (106264).

(Read more about SODIUM)

LIKELY SAFE ...when used in amounts commonly found in foods. Spearmint and spearmint oil have Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally or topically for medicinal reasons (11,12). Spearmint extract up to 900 mg daily has been used safely for up to 90 days (94925,101713,101714). Spearmint tea has been consumed safely twice daily for up to 16 weeks (68500,94923).

PREGNANCY: LIKELY SAFE
when used in the amounts commonly found in foods (4912).

PREGNANCY: POSSIBLY UNSAFE
when used orally during pregnancy in excessive amounts. Animal research suggests that spearmint tea may cause uterine damage (68448). Avoid using in amounts greater than those typically found in foods during pregnancy.

LACTATION: LIKELY SAFE
when used in the amounts commonly found in foods (4912). There is insufficient reliable information available about the safety of spearmint during lactation. Avoid using in amounts greater than those typically found in foods.

(Read more about SPEARMINT)

(Read more about BLACKBERRY)

(Read more about CARDAMOM)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, damiana may lower blood glucose levels (4,25016). This might increase the risk of hypoglycemia in patients taking antidiabetes drugs.  Details Some antidiabetes drugs include glimepiride (Amaryl), glyburide (Diabeta, Glynase PresTabs, Micronase), insulin, metformin (Glucophage), pioglitazone (Actos), rosiglitazone (Avandia), and others.

(Read more about DAMIANA)

AMPHETAMINES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, inhaling eucalyptol may reduce the effectiveness of amphetamines.  Details Animal research suggests that inhaling eucalyptol may reduce the levels of amphetamines in the blood (48987).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, eucalyptus leaf might increase the risk of hypoglycemia.  Details Animal research suggests that eucalyptus leaf might have hypoglycemic activity, and might have additive effects when used with antidiabetes drugs (12871).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, eucalyptus might increase the levels of CYP1A2 substrates.  Details In vitro research suggests that eucalyptus oil might inhibit CYP1A2, although this has not been reported in humans (12479).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, eucalyptus might increase the levels of CYP2C19 substrates.  Details In vitro research suggests that eucalyptus oil might inhibit CYP2C19, although this has not been reported in humans (12479).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, eucalyptus might increase the levels of CYP2C9 substrates.  Details In vitro research suggests that eucalyptus oil might inhibit CYP2C9, although this has not been reported in humans (12479).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, eucalyptus might increase the levels of CYP3A4 substrates.  Details In vitro research suggests that eucalyptus oil might inhibit CYP3A4, although this has not been reported in humans (12479).

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, inhaling eucalyptol might reduce the effectiveness of pentobarbital.  Details Animal research suggests that inhaling eucalyptol reduces the level of pentobarbital that reaches the brain (48987).

(Read more about EUCALYPTUS)

(Read more about EYEBRIGHT)

(Read more about LINDEN)

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, peppermint oil might increase the levels and adverse effects of cyclosporine.  Details In animal research, peppermint oil inhibits cyclosporine metabolism and increases cyclosporine levels. Inhibition of cytochrome P450 3A4 (CYP3A4) may be partially responsible for this interaction (11784). An interaction between peppermint oil and cyclosporine has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, peppermint might increase the levels of CYP1A2 substrates.  Details In vitro and animal research shows that peppermint oil and peppermint leaf inhibit CYP1A2 (12479,12734). However, in clinical research, peppermint tea did not significantly affect the metabolism of caffeine, a CYP1A2 substrate. It is possible that the 6-day duration of treatment may have been too short to identify a difference (96359).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peppermint might increase the levels of CYP2C19 substrates.  Details In vitro research shows that peppermint oil inhibits CYP2C19 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peppermint might increase the levels of CYP2C9 substrates.  Details In vitro research shows that peppermint oil inhibits CYP2C9 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, peppermint might increase the levels of CYP3A4 substrates.  Details Clinical research in healthy volunteers shows that a single dose of peppermint oil 600 mg inhibits CYP3A4 enzymes and increases the AUC of felodipine, a CYP3A4 substrate (11783). However, in vitro research suggests that peppermint oil only inhibits CYP3A4 at very high concentrations (12479).

(Read more about PEPPERMINT)

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = A Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.  Details High intake of dietary sodium can increase systolic and diastolic blood pressure (26222). Also, high intake of sodium may necessitate increased use of antihypertensive medications to achieve blood pressure control in some patients, such as those with chronic kidney disease (26223).

CORTICOSTEROIDS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.  Details Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone (4425).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Altering dietary intake of sodium might alter the levels and clinical effects of lithium.  Details High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion (26225). Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate (26224,26225). Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L (112909). Patients taking lithium should avoid significant alterations in their dietary intake of sodium.

SODIUM-CONTAINING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.  Details The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population (100310). Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.

TOLVAPTAN (Samsca) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.  Details Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia (29406). Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.

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CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, spearmint might alter the sedative effects of CNS depressants.  Details Animal research suggests that (-)-carvone, a major constituent of spearmint, has sedative effects (39800,75758). However, in humans, chewing spearmint-flavored gum induced arousal effects (75699).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of spearmint might increase the risk of liver damage when taken with hepatotoxic drugs.  Details Animal research suggests that drinking spearmint tea for 30 days can increase markers of liver damage, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and cause liver degeneration and necrosis, in a dose-dependent manner (12731). This effect has not been reported in humans.

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General ...Blackberry fruit is commonly consumed as a food without reports of adverse effects. However, a thorough evaluation of safety outcomes for blackberry when used as a medicine has not been conducted.

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General ...Orally, cardamom seems to be well tolerated.

Dermatologic ...Orally, mild skin inflammation due to cardamom has been reported in one participant of a clinical trial (101887). Topically, a case report describes chronic hand dermatitis in a confectioner frequently exposed to cardamom. Skin patch tests were positive for cardamom, and for terpenoids present in the seeds (39875).

Genitourinary ...Orally, dysuria due to cardamom has been reported in one participant of a clinical trial (101887). Also, a case report describes a 5-year-old female who developed hematuria after eating ice cream flavored with cardamom. It resolved spontaneously and there was no re-challenge (95306). It is not clear if cardamom is the direct cause of hematuria in this case.

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General ...Orally, damiana is generally well tolerated. In a rare case, 200 grams of damiana extract has caused tetanus-like convulsions and paroxysms resulting in symptoms similar to rabies or strychnine poisoning (4).

Neurologic/CNS ...Orally, 200 grams of damiana extract has caused tetanus-like convulsions and paroxysms resulting in symptoms similar to rabies or strychnine poisoning (4).

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General ...Orally, diluted eucalyptus oil is generally well tolerated, but the undiluted oil can cause toxicity.
Most Common Adverse Effects:
Orally: Diarrhea, nausea, vomiting.
Topically: Burning, itching, redness, stinging.
Serious Adverse Effects (Rare):
Orally: Signs of toxicity can occur with the undiluted oil at doses as low as 1 mL and include central nervous system depression, shallow respiration, rapid pulse, apnea, coma, and death.
Topically: Prolonged exposure or large amounts of eucalyptus oil can cause agitation, ataxia, drowsiness, muscle weakness, seizures, and slurred speech. The risk of toxicity may be greater in children.
Inhalation (as aromatherapy): Seizures.

Cardiovascular ...Orally, one case of premature ventricular contractions has been reported in a previously healthy 29-year-old male who ingested approximately one ounce of eucalyptus oil (48983).

Dermatologic ...Topically, eucalyptus pollen, leaves, oil, and the constituent eucalyptol can cause contact dermatitis in sensitive people (13303,48931,92856,92858,92859,98497). In some cases, symptoms respond to treatment with topical corticosteroids and tacrolimus (92856). In one case report, transient local redness, burning, and irritation was reported in a 4-year-old child who was bathed in water containing eucalyptus oil. The symptoms resolved within one hour of rinsing the skin with clear water (48983). In a clinical study, treatment with a combination of eucalyptus oil and lemon tea tree oil caused burning, redness, itching, or stinging in up to 20% of the patients. Stinging usually resolved within 10 minutes of application and redness within 30 minutes (19188,98492).

Gastrointestinal ...Orally, eucalyptus oil can cause nausea, vomiting, and diarrhea (48983,48993,48995). Abdominal pain has been reported in a trial of the eucalyptus constituent eucalyptol for inflammatory bowel disease (IBD) (48936).

Immunologic ...A case of IgE-mediated exacerbation of asthma and rhinitis symptoms has been reported in a patient who consumed eucalyptus. Similar worsening of symptoms occurred when the patient inhaled eucalyptus pollen (48957).
Occupational exposure to eucalyptus may cause allergic dermatitis (98497).

Neurologic/CNS ...Orally, eucalyptus oil can cause central nervous system depression, coma, and status epilepticus (12867,48946,48983).
Topically, orally, and by inhalation, eucalyptus oil has been associated with seizures. A systematic review describes the characteristics of 49 children and 61 adults with seizures associated with various routes of administration. Patients with no seizure history were classified as a eucalyptus oil-induced seizure (EOIS), while patients with a history of seizure or susceptibility to seizure were defined as a eucalyptus oil-provoked seizure (EOPS). In EOIS cases, topical use was reported in 74%, inhalation in 22.5%, and ingestion in 3.5%; for EOPS cases, topical use was reported in 79%, inhalation in 16%, and ingestion in 5%. Generalized tonic-clonic seizures are the most prominent type of seizure in EOIS cases (96%). Among EOPS patients, 37% had focal onset motor seizures with impaired awareness, 24% had focal onset aware motor seizures, 13% had focal to bilateral tonic-clonic seizures, and 26% had generalized onset tonic-clonic seizures (107494). One prospective observational study that was included in this systematic review provided additional details on eucalyptus-induced seizures. This study included 18 reports of EOIS and 28 reports of EOPS in adults and children after topical or inhaled use of eucalyptus oil, either alone or in combination with camphor. The time to seizure onset was 0.5-48 hours after topical application, 2-30 minutes after inhalation, and 0.5-6 hours after ingestion. (105028).
One prospective observational study and one case series have described 20 case reports of seizures occurring in children after ingestion of eucalyptus oil. Most of these seizures are generalized tonic-clonic in nature, occur 15-30 minutes after exposure, and do not reoccur following the discontinuation of eucalyptus oil. Seizures have been reported with both overdoses and therapeutic doses (107493,107495) and include cases of both EOIS and EOPS (107495). Additionally, children appear more likely to require intensive care and mechanical ventilation when compared with adult cases (107494).
A case of fever and headache has been reported in a patient who routinely applied a teaspoon of gel containing eucalyptus extract in his throat or nose to treat sore throat or rhinitis (48946).

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General ...There is a limited amount of information on the adverse effects of eyebright. Orally, eyebright has been reported to cause mental confusion, headache, nausea, constipation, cough, dyspnea, insomnia, and polyuria (4). Topically, eyebright applied to the eye has been reported to cause increased eye pressure, itching, redness, vision changes, and photophobia (4). Ophthalmic eyebright products should be used with caution due to the potential for contamination (8,11).

Gastrointestinal ...Orally, eyebright has been reported to cause nausea and constipation (4).

Genitourinary ...Orally, eyebright has been reported to cause polyuria (4).

Neurologic/CNS ...Orally, eyebright has been reported to cause confusion and headache (4).

Ocular/Otic ...Topically, eyebright has been reported to cause increased ocular pressure, lacrimation, pruritus, redness, swelling of eyelid margins, vision changes, and photophobia when applied to the eyes (4). Ophthalmic eyebright products should be used with caution due to the potential for contamination (8,11).

Pulmonary/Respiratory ...Orally, eyebright has been reported to cause cough, dyspnea, and nasal congestion (4).

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General ...There is limited information about the adverse effects of linden. Orally, there is one case report of allergic reaction to linden pollen in a linden flower tea (12). Frequent consumption of linden tea is thought to be associated with cardiac damage, but this seems to be rare (6).
Topically, linden extract can cause contact urticaria (12).

Cardiovascular ...Frequent consumption of linden tea is thought to be associated with cardiac damage, but this seems to be rare (6).

Immunologic ...Orally, there is one case report of allergic reaction to linden pollen in a linden flower tea (12). Topically, there is one case report of contact urticaria following the use of a linden extract-containing shampoo (12).

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General ...Orally, topically, or rectally, peppermint oil is generally well tolerated. Inhaled, peppermint oil seems to be well tolerated. Intranasally, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted. Orally, peppermint leaf seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, anal burning, belching, diarrhea, dry mouth, heartburn, nausea, and vomiting.
Topically: Burning, dermatitis, irritation, and redness.

Dermatologic ...Topically, peppermint oil can cause skin irritation, burning, erythema, and contact dermatitis (3802,11781,31528,43338,68473,68457,68509,96361,96362). Also, a case of severe mucosal injury has been reported for a patient who misused an undiluted over the counter mouthwash that contained peppermint and arnica oil in 70% alcohol (19106).
In large amounts, peppermint oil may cause chemical burns when used topically or orally. A case of multiple burns in the oral cavity and pharynx, along with edema of the lips, tongue, uvula, and soft palate, has been reported for a 49-year-old female who ingested 40 drops of pure peppermint oil. Following treatment with intravenous steroids and antibiotics, the patient's symptoms resolved over the course of 2 weeks (68432). Also, a case of chemical burns on the skin and skin necrosis has been reported for a 35-year-old male who spilled undiluted peppermint oil on a previous skin graft (68572). Oral peppermint oil has also been associated with burning mouth syndrome and chronic mouth ulceration in people with contact sensitivity to peppermint (6743). Also, excessive consumption of mint candies containing peppermint oil has been linked to cases of stomatitis (13114).

Gastrointestinal ...Orally, peppermint oil can cause heartburn, nausea and vomiting, anal or perianal burning, abdominal pain, belching, dry mouth, diarrhea, and increased appetite (3803,6740,6741,6742,10075,11779,11789,17682,68497,68514)(68532,68544,96344,96360,102602,104219,107955). Enteric-coated capsules might help to reduce the incidence of heartburn (3802,4469,6740,11777). However, in one clinical study, a specific enteric-coated formulation of peppermint oil (Pepogest; Nature's Way) taken as 180 mg three times daily was associated with a higher rate of adverse effects when compared with placebo (48% versus 31%, respectively). Specifically, of the patients consuming this product, 11% experienced belching and 26% experienced heartburn, compared to 2% and 12%, respectively, in the placebo group (107955). A meta-analysis of eight small clinical studies in patients with irritable bowel syndrome shows that taking enteric-coated formulations of peppermint oil increases the risk of gastroesophageal reflux symptoms by 67% when compared with a control group (109980). Enteric-coated capsules can also cause anal burning in people with reduced bowel transit time (11782,11789).

Genitourinary ...Orally, a sensitive urethra has been reported rarely (102602).

Hepatic ...One case of hepatocellular liver injury has been reported following the oral use of peppermint. Symptoms included elevated liver enzymes, fatigue, jaundice, dark urine, and signs of hypersensitivity. Details on the dosage and type of peppermint consumed were unavailable (96358).

Immunologic ...One case of IgE-mediated anaphylaxis, characterized by sudden onset of lip and tongue swelling, tightness of throat, and shortness of breath, has been reported in a 69-year-old male who consumed peppermint candy (89479). An allergic reaction after use of peppermint oil in combination with caraway oil has been reported in a patient with a history of bronchial asthma (96344). It is not clear if this reaction occurred in response to the peppermint or caraway components.

Neurologic/CNS ...Orally, headache has been reported rarely (102602).

Ocular/Otic ...Orally, peppermint has been reported to cause blurry vision (3803).

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General ...Orally, sodium is well tolerated when used in moderation at intakes up to the Chronic Disease Risk Reduction (CDRR) intake level. Topically, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Worsened cardiovascular disease, hypertension, kidney disease.

Cardiovascular ...Orally, intake of sodium above the CDRR intake level can exacerbate hypertension and hypertension-related cardiovascular disease (CVD) (26229,98176,100310,106263). A meta-analysis of observational research has found a linear association between increased sodium intake and increased hypertension risk (109398). Observational research has also found an association between increased sodium salt intake and increased risk of CVD, mortality, and cardiovascular mortality (98177,98178,98181,98183,98184,109395,109396,109399). However, the existing research is unable to confirm a causal relationship between sodium intake and increased cardiovascular morbidity and mortality; high-quality, prospective research is needed to clarify this relationship (100312). As there is no known benefit with increased salt intake that would outweigh the potential increased risk of CVD, advise patients to limit salt intake to no more than the CDRR intake level (100310).
A reduction in sodium intake can lower systolic blood pressure by a small amount in most individuals, and diastolic blood pressure in patients with hypertension (100310,100311,106261). However, post hoc analysis of a small crossover clinical study in White patients suggests that 24-hour blood pressure variability is not affected by high-salt intake compared with low-salt intake (112910). Additionally, the available research is insufficient to confirm that a further reduction in sodium intake below the CDRR intake level will lower the risk for chronic disease (100310,100311). A meta-analysis of clinical research shows that reducing sodium intake increases levels of total cholesterol and triglycerides, but not low-density lipoprotein (LDL) cholesterol, by a small amount (106261).
It is unclear whether there are safety concerns when sodium is consumed in amounts lower than the adequate intake (AI) levels. Some observational research has found that the lowest levels of sodium intake might be associated with increased risk of death and cardiovascular events (98181,98183). However, this finding has been criticized because some of the studies used inaccurate measures of sodium intake, such as the Kawasaki formula (98177,98178,101259). Some observational research has found that sodium intake based on a single 24-hour urinary measurement is inversely correlated with all-cause mortality (106260). The National Academies Consensus Study Report states that there is insufficient evidence from observational studies to conclude that there are harmful effects from low sodium intake (100310).

Endocrine ...Orally, a meta-analysis of observational research has found that higher sodium intake is associated with an average increase in body mass index (BMI) of 1. 24 kg/m2 and an approximate 5 cm increase in waist circumference (98182). It has been hypothesized that the increase in BMI is related to an increased thirst, resulting in an increased intake of sugary beverages and/or consumption of foods that are high in salt and also high in fat and energy (98182). One large observational study has found that the highest sodium intake is not associated with overweight or obesity when compared to the lowest intake in adolescents aged 12-19 years when intake of energy and sugar-sweetened beverages are considered (106265). However, in children aged 6-11 years, usual sodium intake is positively associated with increased weight and central obesity independently of the intake of energy and/or sugar-sweetened beverages (106265).

Gastrointestinal ...In one case report, severe gastritis and a deep antral ulcer occurred in a patient who consumed 16 grams of sodium chloride in one sitting (25759). Chronic use of high to moderately high amounts of sodium chloride has been associated with an increased risk of gastric cancer (29405).

Musculoskeletal ...Observational research has found that low sodium levels can increase the risk for osteoporosis. One study has found that low plasma sodium levels are associated with an increased risk for osteoporosis. Low levels, which are typically caused by certain disease states or chronic medications, are associated with a more than 2-fold increased odds for osteoporosis and bone fractures (101260).
Conversely, in healthy males on forced bed rest, a high intake of sodium chloride (7.7 mEq/kg daily) seems to exacerbate disuse-induced bone and muscle loss (25760,25761).

Oncologic ...Population research has found that high or moderately high intake of sodium chloride is associated with an increased risk of gastric cancer when compared with low sodium chloride intake (29405). Other population research in patients with gastric cancer has found that a high intake of sodium is associated with an approximate 65% increased risk of gastric cancer mortality when compared with a low intake. When zinc intake is taken into consideration, the increased risk of mortality only occurred in those with low zinc intake, but the risk was increased to approximately 2-fold in this sub-population (109400).

Pulmonary/Respiratory ...In patients with hypertension, population research has found that sodium excretion is modestly and positively associated with having moderate or severe obstructive sleep apnea. This association was not found in normotensive patients (106262).

Renal ...Increased sodium intake has been associated with impaired kidney function in healthy adults. This effect seems to be independent of blood pressure. Observational research has found that a high salt intake over approximately 5 years is associated with a 29% increased risk of developing impaired kidney function when compared with a lower salt intake. In this study, high salt intake was about 2-fold higher than low salt intake (101261).

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General ...Orally, spearmint is well tolerated.
Most Common Adverse Effects:
Topically: Allergic contact dermatitis or cheilitis in sensitive individuals.

Cardiovascular ...Orally, taking spearmint extract 600 mg daily has been associated with one report of tachycardia in one clinical trial. However, it is not certain that this adverse event was caused by spearmint extract (94925).

Dermatologic ...Orally, drinking 2 cups of spearmint tea with normal amounts of rosmarinic acid has been associated with one report of itchy skin in clinical research (94923).

Gastrointestinal ...Orally, taking spearmint extract 600 mg daily has been associated with dyspepsia in one clinical trial (94925). Taking a higher dose of 900 mg daily has been associated with diarrhea and belching (94925). Drinking 2 cups of spearmint tea with normal amounts of rosmarinic acid has been associated with one report of dry mouth in clinical research. Drinking 2 cups of spearmint tea containing high amounts of rosmarinic acid has been associated with three reports of constipation and one report of loose bowel movements (94923). Taking 1 mL of spearmint oil equivalent to 500 mg of spearmint has been associated with reports of regurgitation in clinical research (75700).

Immunologic ...Topically, spearmint oil and leaves have caused allergic dermatitis (75711,75731,75737). Allergic contact cheilitis has also occurred from spearmint oil in toothpaste or chewing gum (31403,31528,75706,75739,75777,75790). Spearmint oil inhalation has also caused allergic dermatitis (56955). Orally, spearmint leaves have caused allergy-associated swelling of the soft palate. A specific 50 KDa protein in the spearmint was found to be the responsible allergen (94922). In some cases, spearmint allergy was associated with oral lichen planus of the tongue, lips, palate, buccal mucosa, and gingivae. Observational studies suggest that exposure to spearmint is associated with exacerbation of oral lichen planus as confirmed by patch testing (94924,112844).

Neurologic/CNS ...Orally, drinking 2 cups of spearmint tea containing high amounts of rosmarinic acid has been associated with two reports of headache in clinical research (94923).

Psychiatric ...Orally, taking spearmint extract 600 mg daily has been associated with one report of anxiety in one clinical trial. However, it is not certain that this adverse event was caused by spearmint extract (94925).

Other ...Orally, taking spearmint extract 600 mg daily has been associated with one report of increased appetite and weight gain in one clinical trial. However, it is not certain that these adverse events were caused by spearmint extract (94925).

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