Artrospray by Vitaminol Inc.

LIKELY EFFECTIVE

• Cough. Topical camphor formulations seem to reduce acute cough. Details: Camphor is approved by the U.S. Food and Drug Administration as a topical antitussive (chest rub) in concentrations of less than 11% (4814).
• Pain (acute). Topical camphor formulations seem to reduce acute pain. Details: Camphor is approved by the U.S. Food and Drug Administration for topical use as an analgesic and anesthetic in concentrations of 3% to 11% (272,4814). It is used in many topical products to treat pain related to cold sores, insect stings and bites, minor burns, and hemorrhoids (272).
• Pruritus. Topical camphor formulations seem to reduce pruritus. Details: Camphor is approved by the U.S. Food and Drug Administration for topical use as an antipruritic agent in concentrations of 3% to 11% (272,4814).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using topical camphor for acne, there is insufficient reliable information about the clinical effects of camphor for this condition.
• Insect bite. Topical camphor 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 camphor 2%, menthol 2%, and eucalyptus oil 4%, with or without an Indian herb mixture called Trikatu, reduces the papule size of mosquito bites after 1-3 hours (89893). However, it is unclear if the decrease in papule size is related to natural change or the treatment. Also, the effect of camphor alone is not clear.
• Onychomycosis. Although there is interest in using topical camphor for onychomycosis, there is insufficient reliable information about the clinical effects of camphor for this condition.
• Orthostatic hypotension. Oral camphor has only been evaluated in combination with hawthorn; its effect when used alone is unclear. Details: A meta-analysis of 4 small clinical studies in patients with orthostatic hypotension shows that giving single doses of 20-25 drops of a specific combination product (Korodin Herz-Kreislauf-Tropfen) containing camphor and hawthorn modestly increases systolic and diastolic blood pressure when compared with placebo (103620). However, the studies have methodologic problems and, while 2 were conducted in patients with orthostatic hypotension, the others involved healthy young adults or normotensive elderly subjects. The effect of camphor alone for treatment of orthostatic hypotension has not been determined. The combination product used in these studies is not available in the US.
• Osteoarthritis. Although topical camphor is approved for use in the management of acute pain due to its counterirritant effects, it is unclear if it is beneficial for knee osteoarthritis. Details: A small study in patients with knee osteoarthritis shows that applying a topical cream containing camphor 32 mg/gram, glucosamine sulfate30 mg/gram, chondroitin sulfate 50 mg/gram, shark cartilage 140 mg/gram, and peppermint oil 9 mg/gram as needed for 8 weeks seems to moderately reduce pain when compared with placebo (10327). More evidence is needed to rate camphor for these uses.

(Read more about CAMPHOR)

POSSIBLY EFFECTIVE

• Ventilator-associated pneumonia (VAP). Clove mouthwash might reduce the risk of acquiring pneumonia in patients on mechanical ventilation. Details: A large clinical trial in adults in the intensive care unit on mechanical ventilation shows that administration of a clove extract 6.66% mouthwash, 15 mL twice daily for 5 days, results in a 2-fold lower incidence of ventilator-associated pneumonia when compared with chlorhexidine mouthwash (112151).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alveolar osteitis. Although there has been interest in using topical clove for alveolar osteitis, there is insufficient reliable information about the clinical effects of clove for this purpose.
• Anal fissures. It is unclear if topical clove oil is beneficial in patients with anal fissures. Details: Preliminary clinical research in patients with chronic anal fissures shows that applying clove oil 1% cream for 6 weeks heals fissures in 60% of patients by the 3-month follow-up, compared with only 12% of patients who used topical lidocaine 5% cream and stool softeners (43487).
• Cough. Although there has been interest in using oral clove for cough, there is insufficient reliable information about the clinical effects of clove for this purpose.
• Dental plaque. Topical clove has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that using a specific toothpaste (Sudantha, Link Natural Products Ltd.) containing a combination of clove, Acacia chundra Willd., malabar nut, bullet wood tree, black pepper, Indian beech, gall oak, Terminalia, and ginger twice daily for 12 weeks can reduce dental plaque, bleeding, and bacteria counts in the mouth when compared with placebo (43570). Other clinical research shows that administration of a mouth rinse containing clove, tea tree oil, and basil 10 mL twice daily for 21 days is as effective as a commercially available mouth rinse containing thymol, eucalyptol, menthol, and methyl salicylate in reducing dental plaque and gum inflammation (92160). It is unclear whether clove, another ingredient, or a combination of these ingredients is responsible for these effects.
• Diarrhea. Although there has been interest in using oral clove for diarrhea, there is insufficient reliable information about the clinical effects of clove for this purpose.
• Dyspepsia. Although there has been interest in using oral clove for dyspepsia, there is insufficient reliable information about the clinical effects of clove for this purpose.
• Flatulence. Although there has been interest in using oral clove for flatulence, there is insufficient reliable information about the clinical effects of clove for this purpose.
• Gingivitis. Although there has been interest in using topical clove for gingivitis, there is insufficient reliable information about the clinical effects of clove for this purpose.
• Halitosis. Although there has been interest in using oral clove for halitosis, there is insufficient reliable information about the clinical effects of clove for this purpose.
• Hangover. It is unclear if oral clove flower extract is beneficial for reducing hangover severity. Details: Preliminary clinical research in a very small number of healthy males with a history of hangovers shows that taking a clove flower bud polyphenol extract 250 mg prior to drinking brandy (42.8% alcohol) decreases hangover severity scores by around 55% when compared with placebo (100597).
• Hyperhidrosis. It is unclear if topical clove oil is beneficial in patients with hyperhidrosis. Details: Preliminary clinical research in patients with hyperhidrosis of the palms shows that topical application of clove oil 45% in liposome base twice daily for 2 weeks improves hyperhidrosis severity and decreases the rate of sweating by around 34% when compared with a saline control (100596). The validity of these findings is limited by a lack of subject randomization.
• Impaired glucose tolerance (prediabetes). It is unclear if oral clove flower extract is beneficial in patients with prediabetes. Details: Preliminary clinical research in a very small number of patients with prediabetes shows that taking a polyphenolic extract from clove flower buds 250 mg daily for 30 days decreases pre-prandial plasma glucose by 14 mg/dL and postprandial plasma glucose by 40 mg/dL when compared to baseline (100595). The validity of these findings is limited by the very small size of the study and the lack of a control group.
• Mosquito repellent. Small clinical studies suggest that topical clove oil may repel mosquitos for up to 4-5 hours. Details: Preliminary clinical research shows that topical application of undiluted clove oil can repel 100% of mosquitoes for up to 4 hours (43427). Other preliminary research shows that topical application of gel containing clove oil 20% can repel 86% to 97% of mosquitoes for 5 hours (43411).
• Nausea and vomiting. Although there has been interest in using oral clove for nausea and vomiting, there is insufficient reliable information about the clinical effects of clove for this purpose.
• Oral mucositis. Although there has been interest in using topical clove for oral mucositis, there is insufficient reliable information about the clinical effects of clove for this purpose.
• Pain (acute). It is unclear if topical clove is beneficial in patients with acute pain. Details: Preliminary clinical research shows that topical application of a gel containing ground cloves, applied as 4 grams of gel for 5 minutes prior to dental anesthesia injection, can reduce needle stick pain when compared with placebo. The effect of the clove gel on pain seems to be comparable to benzocaine 20% gel (43448).
• Premature ejaculation. Topical clove has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that administration of a multi-ingredient cream preparation (SS Cream) containing clove flower, Panax ginseng root, Angelica root, Cistanches deserticola, Zanthoxyl species, Torlidis seed, Asiasari root, cinnamon bark, and toad venom to the glans penis, one hour prior to intercourse and washed off immediately before intercourse, increases ejaculatory latency time by over 4-fold when compared with placebo in adults with premature ejaculation (2537). It is unclear whether clove, another ingredient, or a combination of these ingredients is responsible for these effects.
• Pruritus. There is limited evidence on the topical use of clove oil in patients with chronic pruritus. Details: Preliminary clinical research in patients with chronic pruritus shows that applying clove oil 10% in petroleum jelly to the skin twice daily for 2 weeks reduces the daily duration of itching by 48 minutes and improves symptom severity and disability scores when compared with placebo (96950). More evidence is needed to rate clove for these uses.

(Read more about CLOVE)

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).
• Fever. Inhaled eucalyptus oil has only been evaluated in combination with other ingredients for fever following vaccination; its effect when used alone is unclear. Details: A large clinical study in adults shows that inhaling aromatherapy with eucalyptus oil 0.05 mL in combination with topical application of tea tree oil 0.05 mL on the affected arm every 2 hours while awake for 3 days after COVID-19 vaccination reduces the frequency of self-reported fever when compared with control during the first 48 hours after vaccination (113141). The interpretation of these results is limited by baseline group differences in receipt of various COVID-19 vaccine products, which may differ in side effect frequency. Also, it is unclear if these effects are due to eucalyptus, tea tree oil, or the combination.
• 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.
• Injection site reaction. Inhaled eucalyptus oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in adults shows that inhaling aromatherapy with eucalyptus oil 0.05 mL in combination with topical application of tea tree oil 0.05 mL on the affected arm every 2 hours while awake for 3 days after COVID-19 vaccination improves self-reported muscle ache, localized swelling, pain, and fever, but not erythema, joint pain, or headache when compared with control in the first 24 hours after vaccination. However, at 24-48 hours, only localized swelling and fever were improved in the group using eucalyptus and tea tree oil (113141). The interpretation of these results is limited by baseline group differences in receipt of various COVID-19 vaccine products, which may differ in side effect frequency. Also, it is unclear if these effects are due to eucalyptus, tea tree oil, or the combination.
• 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.

(Read more about EUCALYPTUS)

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). A meta-analysis of 3 randomized controlled trials in adults receiving chemotherapy also shows that peppermint oil aromatherapy moderately improves nausea and vomiting when compared with control. However, the results of this analysis are limited by heterogenous application methods, doses, and durations of peppermint therapy (114761). 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. Another small clinical trial in children receiving chemotherapy for acute leukemia shows that aromatherapy with peppermint oil 2%, 0.2 mL inhaled over 3 minutes immediately prior to 3 consecutive chemotherapy sessions, added to standard care (e.g. antiemetic medications), reduces overall incidence of nausea by 40%, and improves nausea and vomiting severity scores, when compared with no additional interventions. These results were similar to those receiving Swedish massage prior to chemotherapy sessions (114759).
• 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.
• Athletic performance. It is unclear if oral peppermint oil is beneficial for athletic performance. Details: Preliminary clinical research in trained adult runners shows that taking peppermint essential oil, 0.05 mL diluted in 500 mL of water, orally once 30 minutes before exercise improves running time to exhaustion by 11% when compared with placebo (112742). Another very small clinical study in elite soccer athletes shows that use of a specific peppermint essential oil (doTERRA), 1 drop rubbed into hands and inhaled with 5 deep breaths, does not improve jump performance metrics when compared with placebo (114760).
• 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). Other preliminary clinical research in elderly adults with dementia who require oral care assistance shows that cleaning the mouth with a mixture of peppermint oil, tea tree oil, and lemon essential oils diluted to 0.5%, applied via gauze, twice daily for 7 days improves halitosis scores and oral condition scores when compared with placebo (112957).
• 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. It is unclear if inhaled peppermint oil is beneficial for menopausal symptoms. Details: Preliminary clinical research in adults with menopausal symptoms shows that receiving aromatherapy as 2 drops of peppermint oil with upper extremity massage and for 30 minutes twice weekly for 4 weeks moderately improves menopause symptom scores, including both somatic symptoms and urogenital symptoms, when compared with placebo (112745).
• Migraine headache. It is unclear if intranasal or inhaled 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. Other preliminary clinical research in pediatric patients with migraine or other chronic headaches shows that receiving aromatherapy with peppermint oil over 10 minutes during a footbath does not improve pain or anxiety scores when compared with control (112746).
• 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 or topical 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). Another small open-label study in adults undergoing venipuncture for dialysis shows that topical application of peppermint gel 5 mL reduces pain scores by approximately 50% when compared with no intervention. These results were similar to using a cold compress (114758). Additionally, a small open-label study in children undergoing a dental procedure, shows that topical application of peppermint oil 0.2% , moderately improves pain scores after a buccal injection when compared with lidocaine spray 15% (114757).
• 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. In contrast, a small clinical trial in adults undergoing port catheter placement shows that application of a specific aromatherapy patch containing peppermint and lavender (Elequil Aromatabs, Beekley Medical) preoperatively does not reduce PONV rescue treatment when compared with placebo (114623). Another small clinical trial in adults with anxiety undergoing total hip or knee arthroplasty shows that application of the same patch containing peppermint and lavender every 12 hours for 6 doses does not reduce overall PONV when compared with placebo (114622).
• Postoperative pain. It is unclear if inhaled peppermint oil is beneficial for postoperative pain. Details: Preliminary clinical research in adults undergoing open heart cardiac surgery shows that receiving aromatherapy with peppermint oil 10%, 0.1 mL, three times daily for 7 doses moderately improves pain scores when compared with placebo (112747). Other preliminary clinical research in adults undergoing lumbar discectomy surgery shows that receiving aromatherapy with peppermint oil 5 drops once postoperatively modestly improves pain scores and anxiety scores when compared with no intervention (112744). A small clinical trial in adults undergoing port catheter placement shows that application of a specific aromatherapy patch containing peppermint and lavender (Elequil Aromatabs, Beekley Medical) preoperatively does not improve pain scores or reduce opioid rescue treatment in the immediate post-operative period when compared with placebo (114623). Another small clinical trial in adults with anxiety undergoing total hip or knee arthroplasty shows that application of the same patch containing peppermint and lavender every 12 hours for 6 doses modestly reduceses opioid consumption on postoperative day 2, but not day 1, 7, or 30, when compared with placebo (114622). However, these changes are unlikely to be clinically relevant. In addition, it is unclear if any potential effects are due to peppermint, lavender, or the combination.
• Postoperative recovery. Inhaled peppermint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults undergoing port catheter placement shows that application of a specific aromatherapy patch containing peppermint and lavender (Elequil Aromatabs, Beekley Medical) preoperatively does not shorten postoperative length of stay when compared with placebo (114623).
• Postoperative sleep disturbance. It is unclear if inhaled peppermint oil is beneficial for postoperative sleep disturbance. Details: Preliminary clinical research in adults undergoing open heart cardiac surgery shows that receiving aromatherapy with peppermint oil 10%, 0.1 mL, three times daily for 7 doses modestly improves sleep scores when compared with placebo (112747).
• 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.

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POSSIBLY SAFE ...when used topically in low concentrations, short-term. Concentrations ranging from 0.1% to 11% seem to be safe for short-term application to intact skin (272,10327,89893). ...when used by inhalation, appropriately. Even relatively dilute concentrations of camphor can irritate the nose and sinuses. However, it is difficult to determine a safe concentration of inhaled camphor. The Occupational Safety and Health Administration (OSHA) has set a permissible workplace air exposure to synthetic camphor of no more than 2 parts per million (ppm) (272,105033). It is unclear how this correlates to the exposure obtained from a camphor balm or steam bath.

LIKELY UNSAFE ...when used topically on broken or injured skin. Application of camphor to broken skin can result in systemic absorption and toxicity (272). ...when inhaled in large concentrations, which can result in systemic toxicity (13445,39666). However, it is difficult to determine a safe concentration of inhaled camphor. The National Institute for Occupational Safety and Health (NIOSH) has determined an Immediately Dangerous to Life or Health Concentration (IDLH) of synthetic camphor in workplace air to be 200 ppm (105033). It is unclear how this correlates to the exposure obtained from a camphor balm or steam bath.

UNSAFE ...when used orally. Although a particular oral product containing camphor and hawthorn (Korodin Herz-Kreislauf-Tropfen) has been used safely by adults in some clinical studies (103620), ingestion of camphor can cause significant toxicity, including death (13442). Oral preparations of camphor are no longer available in the US (13442).

CHILDREN: POSSIBLY UNSAFE
when used topically (4814). Young children might be more susceptible to the adverse effects associated with even minor systemic absorption of camphor. The American Academy of Pediatrics recommends that camphor not be used in treating children (4814).

CHILDREN: UNSAFE
when used orally. Ingestion of camphor can cause significant toxicity including death (4814). The American Academy of Pediatrics recommends that available non-prescription topical camphor products should not exceed 11% strength to limit toxicity if accidentally ingested by children (4814).

PREGNANCY AND LACTATION: UNSAFE
when used orally. Ingestion of camphor can cause serious toxicity including death (13442). There is insufficient reliable information available about the safety of using camphor topically during pregnancy and lactation.

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LIKELY SAFE ...when used orally in amounts commonly found in foods. Clove, clove oil, and eugenol have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).

POSSIBLY SAFE ...when clove oil is applied topically (272). A clove oil 1% cream has been applied to the anus with apparent safety for up to 6 weeks (43487). A liposome-based product containing clove oil 45% has been applied to the palms with apparent safety for up to 2 weeks (100596).

LIKELY UNSAFE ...when clove smoke is inhaled. Smoking clove cigarettes can cause respiratory injury (17,43599). ...when clove oil is injected intravenously. This can cause pulmonary edema, hypoxemia, and acute dyspnea (16384). There is insufficient reliable information available about the safety of using clove orally in medicinal amounts.

CHILDREN: LIKELY UNSAFE
when clove oil is taken orally. Ingesting 5-10 mL of undiluted clove oil has been linked to reports of coagulopathy, liver damage, and other serious side effects in infants and children up to 3 years of age (6,17,43385,43395,43419,43457,43652).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts found in foods (4912). Clove, clove oil, and eugenol have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912). There is insufficient reliable information available about the safety of using clove in medicinal amounts during pregnancy and lactation; avoid using.

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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.

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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.

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HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of camphor with other hepatotoxic drugs might increase the risk of liver damage.  Details There have been a few case reports of transient elevations in liver enzymes in adults after oral or topical use of camphor (39576,97260). There has also been one case of hepatotoxicity in an infant after topical camphor use (4608).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, clove oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Laboratory research suggests that eugenol, a constituent of clove, has antiplatelet activity (12889,43558,43650,43654). This interaction has not been reported in humans.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of clove extracts with antidiabetes drugs might increase the risk of hypoglycemia.  Details Clinical and laboratory research suggest that polyphenol extracts from clove flower buds might lower blood glucose levels (100595). Dosing adjustments for insulin or oral hypoglycemic agents may be necessary when taken with clove. Monitor blood glucose levels closely.

IBUPROFEN (Advil, others) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, topical application of clove oil with ibuprofen might increase the absorption and side effects of topical ibuprofen.  Details Laboratory research shows that topical application of clove oil increases the absorption of topical ibuprofen (98854). This interaction has not been reported in humans.

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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).

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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).

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General ...Orally, camphor is unsafe and can cause significant toxicity. Topically and by inhalation, camphor seems to be generally well-tolerated.
Most Common Adverse Effects:
Oral: Gastrointestinal and ocular symptoms of toxicity can occur within 5-90 minutes of ingestion. Neurological symptoms can occur with ingestion of quantities greater than 50 mg/kg.
Topically: Dermatitis and skin irritation.
Inhalation: Nose and sinus irritation.
Serious Adverse Effects (Rare):
All routes: Systemically absorbed camphor can lead to seizures, respiratory depression, coma, and death.

Cardiovascular ...Case reports of intoxication due to accidental or intentional consumption have included peripheral circulatory shock and sinus tachycardia (39649,97261). A 54-year-old female with a history of cardiomyopathy and atrial fibrillation developed several episodes of ventricular tachycardia and fibrillation requiring use of a defibrillator after ingestion of Vicks VapoRub, containing 4.8% camphor. She had been taking 7.5 grams of the product weekly, and took an additional 150 grams the week prior to admission. After discontinuing all camphor-containing products and receiving supportive measures, the patient's symptoms and laboratory abnormalities returned to normal (97260).

Dermatologic ...Orally, camphor can cause significant toxicity. In more severe toxicity, general pallor and cyanosis of the lips occur (13442,13444). Topically, camphor is not as likely to cause adverse effects. But some amount of camphor can be absorbed through intact skin. Topical use of camphor has been associated with contact eczema (13445).
Warn patients not to heat products such as Vicks VapoRub in the microwave. Serious burns have occurred when the product is superheated in the microwave (13446).

Gastrointestinal ...Orally, camphor can cause significant toxicity. Symptoms of camphor toxicity occur rapidly within 5-90 minutes of ingestion. Burning of the mouth and throat, and nausea and vomiting are the first symptoms (13442,13444,39589,39626,39646,39658).

Hepatic ...Orally, camphor can cause transient elevations of liver enzymes in both adults and children. There is also a report of increased liver enzymes in an infant who received a camphor-containing topical cold remedy. The enzymes affected included aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and lactate dehydrogenase (LDH). The liver enzymes normalized after stopping the topical cold formula (4608).There is also a report of increased liver enzymes in a 35-year-old adult following "coining" with a balm containing camphor, which involves applying the balm and then rubbing the area with a coin until ecchymosis. The liver enzymes normalized after stopping treatment (39576). Elevated liver enzymes were also reported in a 54-year-old female after oral ingestion of Vicks VapoRub, containing 4.8% camphor. She had been taking 7.5 grams of the product weekly, and took an additional 150 grams the week prior to admission. After discontinuing all camphor-containing products and receiving supportive measures, the patient's symptoms and laboratory abnormalities returned to normal (97260).

Neurologic/CNS ...Orally, camphor can cause significant toxicity. Neurological symptoms occur with ingestion of greater than 50 mg/kg. These symptoms include irritability, exaggerated tendon reflexes, tonic muscular contraction, myoclonic jerks, seizures, confusion, coma, and apnea. Seizures are sometimes the first manifestation of serious toxicity (13442,13444,39560,39589,39629,39646,39649,39658,39660). In children under 6 years of age, doses as low as 700-800 mg, and possibly as low as 500 mg, have caused serious seizures, resulting in respiratory failure and death (13442,13444,39589). Asymptomatic patients who have ingested camphor should be observed for at least 3 hours in a hospital. A 12-hour observation period may be prudent as seizures have occurred 9 hours after ingestion in apparently recovering patients. In patients who survive, symptoms usually resolve within 24 hours, although there are reports of persistent abnormalities for days to weeks. Long-term sequelae have not been reported after resolution of symptoms (13442,13443). In one case, a 10-year-old boy who intentionally ingested cold remedy transdermal patches containing a total of camphor 300 mg experienced mental status changes and tremulousness (39626).
Topically, camphor is not as likely to cause adverse effects, but small amounts can be absorbed through intact skin. A considerable amount of camphor can also be absorbed when inhaled. Excessive use of camphor, either topically or by inhalation, can result in the development of systemic toxicity (13445,39666). Topically and by inhalation, camphor has been associated with the occurrence of seizures. In one prospective observational study, there were 20 reports of new onset seizures and 29 reports of recurrent seizures in adults and children after use of camphor, either alone or in combination with eucalyptus oil. Most cases of seizure with topical use occurred 0.5-24 hours after topical application to the chest, neck, or face. Most cases of seizure with inhalation occurred about 2-30 minutes after steam inhalation of camphor (105028).

Ocular/Otic ...Orally, camphor can cause significant toxicity. Ocular symptoms such as mydriasis and darkening of vision may occur (13442,13444). There is a case report of blurry vision following accidental ingestion of camphor (39667).
There is a case report of self-inflicted conjunctival inflammation after using camphor in the eyes (39624). Warn patients not to heat products such as Vicks VapoRub in the microwave. Eye injury has occurred when the product is superheated in the microwave (13446).

Pulmonary/Respiratory ...When inhaled in large enough concentrations, camphor can irritate the nose and sinuses. However, it is difficult to determine a safe concentration of inhaled camphor (105033).
A 54-year-old females with a history of asthma developed shortness of breath, hypoxemia, and respiratory acidosis after oral ingestion of Vicks VapoRub, containing 4.8% camphor. She had been taking 7.5 grams of the product weekly, and took an additional 150 grams the week prior to admission. After discontinuing all camphor-containing products and receiving supportive measures, the patient's symptoms and laboratory abnormalities returned to normal (97260).

Other ...A smell of camphor from the breath and body have been reported following oral intake of camphor (39560,39589,97261).

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General ...Orally, clove is well tolerated when consumed as a spice; however, clove oil in doses of only 5-10 mL can be toxic in children. Topically, clove is generally well tolerated. When inhaled or used intravenously, clove may be unsafe.
Most Common Adverse Effects:
Topically: Burning, contact dermatitis, dental decay, itching, mucous membrane irritation, tingling, ulcers.
Inhaled: Dental decay, hypertension, itching, tachycardia.
Serious Adverse Effects (Rare):
Orally: Liver failure, respiratory distress.
Inhaled: Pneumonitis, pulmonary edema, respiratory distress.

Cardiovascular ...Smoking clove cigarettes increases heart rate and systolic blood pressure (12892).

Dental ...Population research has found that the risk of dental decay is increased in clove cigarette smokers (43332). Repeated topical application of clove in the mouth can cause gingival damage and skin and mucous membrane irritation (4,272,512). Eugenol, a constituent of clove and a material commonly found in dentistry, has been associated with side effects including gum inflammation and irritation (43365,43373,43522).

Dermatologic ...The American Dental Association has accepted clove for professional use, but not nonprescription use, due to potential damage to soft tissue that may be induced by clove application. In clinical research, small aphthous-like ulcers appeared in the area of the mouth where clove gel was applied in four participants (43448). Skin irritation and stinging have been reported with clove oil application (43338,43626). In a 24-year-old, exposure to a clove oil spill resulted in permanent local anesthesia and anhidrosis, or lack of sweating, at the affected area (43626).

Endocrine ...A case of hypoglycemia and metabolic acidosis have been reported after administration of one teaspoon of clove oil to a seven-month-old infant (43457). A case of electrolyte imbalance following accidental ingestion by a seven-month-old has also been reported (6).

Hematologic ...A case of disseminated intravascular coagulation has been reported in a 2-year-old patient after consuming between 5-10 mL of clove oil. The patient was treated with heparin, fresh frozen plasma, protein C, factor VII, and antithrombin III. On the fifth day, the patient started to improve and made a full recovery (43652).

Hepatic ...There are three cases of hepatic failure occurring in children after ingestion of 5-10 mL of clove oil (43395,43419,43652). Liver injury also occurred in a 3-year-old male (96949). These patients were successfully treated with N-acetylcysteine. The course of liver injury seems to be milder and shorter with early N-acetylcysteine treatment (43395,43419,96949). Another patient, who also presented with disseminated intravascular coagulation, was successfully treated with heparin, fresh frozen plasma, protein C, factor VII, and antithrombin III (43652).

Immunologic ...Contact dermatitis and urticaria has been reported following topical exposure to clove oil or eugenol, a constituent of clove oil (12635,43339,43606,43346).

Neurologic/CNS ...CNS depression has been reported in a 7-month-old who was given one teaspoon of clove oil accidentally in place of mineral oil for diarrhea. The patient was successfully treated with supportive care and gastric lavage (43457). A case of confusion and inability to speak has been reported secondary to oral exposure to clove oil and alcohol. The patient required intubation and was successfully treated with thiamine and normal saline (43580). Seizure and coma have been reported in a two-year-old male after ingesting 5-10 mL of clove oil (43652).

Pulmonary/Respiratory ...Clove cigarettes have been associated with throat and chest tightness (43337), pulmonary edema (43618), and fatal aspiration pneumonitis (43599). The causative factor may be clove alone or clove along with other substances found in cigarettes. Clove cigarettes contain significant amounts of nicotine, tar, and carbon monoxide and increase plasma levels of nicotine and exhaled carbon monoxide, which might cause long-term health effects similar to tobacco smoking (12892). According to the American Medical Association, inhaling clove cigarette smoke has been associated with severe lung injury in a few susceptible individuals with prodromal respiratory infection. Also, some individuals with normal respiratory tracts have apparently suffered aspiration pneumonitis as the result of a diminished gag reflex induced by a local anesthetic action of eugenol, which is volatilized into the smoke (43602).
Intravenous injection of clove oil in a 32-year-old female resulted in hypoxia, acute dyspnea, interstitial and alveolar infiltrates, and non-cardiogenic pulmonary edema. The patient was managed with supplemental oxygen and recovered over the next seven days (16384).
Occupational exposure to eugenol, a constituent of clove, has also been reported to cause asthma and rhinitis (43492).

Renal ...Proteinuria and other urinary abnormalities were observed in a seven-month-old infant given one teaspoon of clove oil accidentally in place of mineral oil for diarrhea. The patient was successfully treated with supportive care and gastric lavage (43457).

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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 ...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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