Kaprex by Nutri Ltd

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral hops-derived bitter acids are beneficial for memory and attention in patients with age-related cognitive decline. Details: A small exploratory clinical study in older adults aged 45-64 years, with self-awareness of cognitive decline, shows that taking matured hops bitter acids (Kirin Holdings Co. Ltd) 35 mg daily for 12 weeks does not improve memory, attention, or performance on most cognitive tests when compared with placebo (102899). A follow-up clinical study in patients aged 45-69 years with subjective cognitive decline shows that taking the same dose of the same product for 12 weeks also does not improve memory, learning, or selective attention, but might improve divided attention as measured on the Symbol Digit Modalities Test (SDMT), when compared with placebo (105953). Both studies were funded by the supplement manufacturer and conducted in Japan; it is unclear if these findings are generalizable to other geographic locations.
• Anxiety. Although there is interest in using oral hops for anxiety, there is insufficient reliable information about the clinical effects of hops for this condition.
• Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral hops for ADHD, there is insufficient reliable information about the clinical effects of hops for this condition.
• Body odor. Although there is interest in using topical hops to reduce body odor, there is insufficient reliable information about the clinical effects of hops for this purpose.
• Insomnia. Taking oral hops extract in combination with valerian root extract seems to be modestly beneficial in patients with insomnia. However, the effect of hops extract when used alone is unclear. Details: In patients with diagnosed sleep disorders, taking hops extract in combination with valerian root for at least 28 days seems to be beneficial. One clinical study in adults with mild insomnia shows that taking two tablets of a combination product containing a total of 83.8 mg hops extract and 374 mg valerian root extract nightly seems to modestly improve subjective sleep measures, including sleep latency, when compared with placebo, after 28 days. However, there was no difference in efficacy between treatment groups after only 14 days (15018). Additionally, a small clinical study in patients with non-organic sleep disorders shows that taking a specific fixed combination product (Ze91019) containing hops extract 120 mg and valerian root extract 500 mg daily for 28 days improves sleep latency when compared with placebo (19413). It is unclear if taking hops and valerian root as a single dose is beneficial in healthy patients. One small clinical study in healthy volunteers with poor sleep shows that taking a specific preparation (Dormeasan, Bioforce AG) containing hops extract 460 mg and valerian root extract 460 mg dissolved in 50 mL of honey water once at night increases total sleep time and time spent in deep sleep when compared with placebo (19418). However, another preliminary clinical study in healthy adults shows that taking a single dose of a specific product (Hova, Zyma S.A.) containing hops extract 200 mg and valerian root extract 400 mg does not improve sleep latency when compared with placebo (6248). Research also shows that taking certain combination products containing hops and at least two other ingredients can improve sleep quality. These combination products have combined hops with lemon balm and valerian (Valerina Natt) (19417); or passionflower and valerian (NSF-3, M/s Tablets India) (88193,89406). However, other combination products have not been beneficial. These have combined hops with soya oil, soya lecithin, and cannabis (Cyclamax, Persee Medica) (55382); or with vitamin B6, zizyphus extract, hydrolyzed milk protein (Lactium), and magnesium oxide (LZ Complex3, Sanofi) (95971).
• Dyspepsia. Although there is interest in using oral hops-derived bitter acids for dyspepsia, there is insufficient reliable information about the clinical effects of hops for this condition.
• Lactation. Although there is interest in using oral hops for increasing lactation, there is insufficient reliable information about the clinical effects of hops for this purpose.
• Menopausal symptoms. It is unclear if oral hops extract is beneficial in patients with menopausal symptoms. Details: Small clinical studies in patients with menopausal symptoms show that taking a specific hops extract (MenoHop, Biodynamics) 75.1-300 mg standardized to contain 100-200 mcg of 8-prenylnaringenin daily does not improve menopausal symptoms, including hot flashes, after 8-12 weeks of treatment when compared with placebo (55338,55370).
• Obesity. It is unclear if administering bitter hops extract intraduodenally or intragastrically is beneficial in patients with obesity. Details: A very small clinical study in healthy young adult males shows that intraduodenal or intragastric administration of bitter hops extract 100-250 mg once does not affect appetite perception, gastrointestinal symptoms, or subsequent energy intake when compared with control (112233). It is unclear if these results are generalizable to individuals with overweight or obesity.
• Overactive bladder. Oral hops extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: An observational study in females with overactive bladder suggests that taking a specific combination product (Granu Fink femina, Omega Pharma) containing hops extract 18 mg, sweet sumac bark extract 56 mg, and pumpkin seed oil 227 mg three times daily for 12 weeks decreases the frequency of urination from an average of 0.9 to 0.4 episodes daily and the frequency of leakage when compared with baseline. The study also shows this specific combination product (Granu Fink femina, Omega Pharma) improves quality of life when compared with baseline (103253). The validity of these findings is limited by the lack of a control group. Also, it is unclear if these findings are due to hops extract, other ingredients, or the combination.
• Psychological well-being. It is unclear if drinking non-alcoholic beer containing matured hops bitter acids is beneficial in healthy adults. Details: A clinical study in healthy adults shows that consuming 350 mL of non-alcoholic beer containing matured hops bitter acids 35 mg (Kirin Holdings Co. Ltd) daily for 3 weeks improves mood scores on the Profile of Mood States 2 (POMS2) and Two-dimensional Mood Scale (TDMS) when compared with baseline (107813). The validity of these findings is limited by the lack of a control group.
• Sexual dysfunction. It is unclear if topical hops gel is beneficial in patients with postmenopausal vaginal atrophy. Details: A small clinical study in adults with postmenopausal vaginal atrophy shows that applying intravaginal topical gel containing hops extract (Barij Essence) daily for 7 days and then twice weekly thereafter for 2 months does not improve sexual desire, sexual arousal, vaginal lubrication, satisfaction, orgasm, sexual pain, or overall measures of sexual dysfunction when compared with intravaginal estradiol (112125). The validity of these effects is limited by baseline differences between groups.
• Shift work disorder. It is unclear if drinking non-alcoholic beer containing hops is beneficial in patients with shift work disorder. Details: A small open-label clinical study in healthy female nurses working rotating or night shifts shows that drinking 333 mL of non-alcoholic beer containing hops (San Miguel 0% alcohol) at dinner for 2 weeks reduces sleep latency by about 8 minutes, total activity during the night, andanxiety when compared with baseline. However, it does not appear to increase the duration of sleep (55403). The validity of these findings is limited by the lack of a control group and unconfirmed hops content in the beer.
• Vaginal atrophy. Topical hops extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: An open-label, multicenter clinical study in postmenopausal patients with vaginal atrophy shows that inserting 2.5 grams of a vaginal gel containing hops extract 1%, hyaluronic acid, liposomes, and vitamin E (Gynomunal Vaginal gel or Esvegyne, Polichem SA) into the vagina daily for one week followed by twice weekly for 11 weeks reduces vaginal dryness, burning, itching, and rash when compared with baseline (55339). The validity of these findings is limited by the lack of a control group. Also, it is unclear if these effects are due to hops, other ingredients, or the combination.
• Venous leg ulcers. Although there is interest in using topical hops for venous leg ulcers, there is insufficient reliable information about the clinical effects of hops for this condition. More evidence is needed to rate hops for these uses.

(Read more about HOPS)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dyspepsia. Oral olive leaf extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in healthy adults shows that taking a specific combination product containing olive leaf extract 24% and prickly pear cactus 33% (Mucosave, Bionap S.R.L.) 400 mg daily for 8 weeks seems to improve dyspepsia and other gastrointestinal symptoms when compared with placebo (105904). It is unclear if this benefit would occur in patients with clinically diagnosed dyspepsia.
• Exercise-induced respiratory infections. It is unclear if oral olive leaf extract is beneficial for reducing respiratory infections from exercise. Details: A small clinical study in high school athletes shows that taking one tablet of olive leaf extract providing eleuropein 100 mg daily for 2 months during training season does not reduce the incidence of the common cold when compared with placebo. While it may reduce the number of sick days by 28%, a sub-group analysis suggests that this reduction is only evident in female athletes (101860).
• Gastroesophageal reflux disease (GERD). Although there is interest in using oral olive leaf for GERD, there is insufficient reliable information about the clinical effects of olive for this condition.
• Herpes zoster (shingles). Although there is interest in using oral olive leaf for shingles, there is insufficient reliable information about the clinical effects of olive for this condition.
• Influenza. Although there is interest in using oral olive leaf for influenza, there is insufficient reliable information about the clinical effects of olive for this condition.
• Metabolic syndrome. It is unclear if oral olive leaf extract is beneficial for improving body composition and cardiovascular risk factors in patients with metabolic syndrome. Details: A small clinical trial in overweight, middle-aged males at risk for metabolic syndrome shows that taking four capsules of olive leaf extract providing oleuropein 51.1 mg and hydroxytyrosol 9.7 mg daily for 12 weeks improves insulin sensitivity by 15% when compared with placebo. However, body composition, blood pressure, cholesterol levels, and other cardiovascular risk factors were not improved (92245).
• Osteoarthritis. It is unclear if oral olive fruit or leaf extract is beneficial for improving osteoarthritis. Details: Preliminary clinical research shows that taking a freeze-dried aqueous extract of olive fruit 400 mg daily for 8 weeks decreases pain and increases mobility in people with osteoarthritis (14844). Other preliminary clinical research in adults with knee osteoarthritis shows that taking olive leaf extract 50.1 mg daily for 4 weeks improves overall pain measurements by 14%, compared to only 4% in the placebo group. However, many individual measurements of pain are not improved (92252).
• Osteoporosis. It is unclear if oral olive leaf extract is beneficial for osteoporosis. Details: Clinical research shows that taking olive leaf extract (Bonolive, BioActor BV) 250 mg daily for 12 months, along with elemental calcium 400 mg daily, increases osteocalcin levels by about 32% when compared to baseline; this increase was significant when compared to those taking calcium 400 mg plus placebo, who showed a 6% decrease in osteocalcin levels. However, taking olive leaf extract does not significantly increase bone mineral density of the lumbar spine or femur neck when compared with placebo (92247).
• Rheumatoid arthritis (RA). It is unclear if oral olive fruit extract is beneficial for improving RA symptoms. Details: Preliminary clinical research in adults with RA shows that taking an aqueous freeze-dried extract of olive fruit 400 mg daily for 8 weeks does not improve symptoms when compared with control (14844). More evidence is needed to rate the effectiveness of olive for these uses.

(Read more about OLIVE)

POSSIBLY EFFECTIVE

• Memory. Oral rosemary seems to improve memory in young adults. It is unclear if rosemary aromatherapy improves memory. Details: Clinical research in healthy adults shows that taking rosemary 500 mg orally twice daily for one month improves memory by approximately 14% when compared with placebo (98536). Other preliminary clinical research shows that applying four drops of pure rosemary essential oil (Tisserand Aromatherapy) to an aromatherapy diffuser pad 5 minutes before a single test period can improve the quality, but not the speed, of memory recall, and increase alertness and contentment more than lavender aromatherapy or no aroma (18323). Rosemary aromatherapy has also been evaluated for improving memory in adults with kidney failure. A small clinical study in patients (mean age 53 years) undergoing hemodialysis shows that aromatherapy with rosemary essential oil three times weekly for 1 month does not improve medication adherence or measures of prospective and retrospective memory when compared with a control group. In this study, five drops of rosemary essential oil were applied to gauze, which was then placed 10 cm from the patient's nose for 30 minutes starting 1 hour after hemodialysis (109559).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abortion. Although there has been interest in the use of oral rosemary as an abortifacient, there is insufficient reliable information about the clinical effects of rosemary for this purpose.
• Age-related cognitive decline. It is unclear if oral rosemary is beneficial for age-related cognitive decline. Details: A small clinical study in healthy individuals aged 65-90 years shows that a single 750 mg dose of powdered rosemary leaf in tomato juice may improve memory speed. However, higher single doses of 1500-6000 mg seem to have a deleterious effect on memory speed. For other measures of attention and memory, there were no clear benefits across the range of doses from 750-6000 mg (18246). Oral rosemary has also been evaluated in combination with other ingredients. A small clinical study in healthy adults aged 62 years or younger shows that taking a combination product containing equal parts rosemary, lemon balm, and sage twice daily for 2 weeks modestly improves word recall when compared with placebo. However, it does not appear to have benefit in adults aged 63 years and older (97277). It is unclear if any benefit is due to rosemary, other ingredients, or the combination.
• Alopecia areata. Topical rosemary oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that rosemary oil 114 mg, in combination with lavender oil 108 mg, thyme oil 88 mg, and cedarwood oil 94 mg, mixed with jojoba oil 3 mL and grapeseed oil 20 mL and applied topically to the scalp, improves hair growth in 44% of patients, compared with 15% of those receiving placebo. This combination was massaged into the scalp for a minimum of 2 minutes, followed by wrapping the head in a warm towel, every night for 7 months (5177).
• Androgenic alopecia. It is unclear if topical rosemary is beneficial for androgenic alopecia. Details: Preliminary clinical research shows that applying rosemary oil (Barij Essence Pharmaceutical Company) 1 mL to the scalp twice daily for 6 months is as effective as minoxidil 2% for increasing hair count in patients with androgenic alopecia (91729).
• Depression. It is unclear if oral rosemary is beneficial for major depressive disorder. Details: A small clinical trial among adults newly diagnosed with major depressive disorder and recent initiation of antidepressant medication shows that taking rosemary dried leaf extract 650 mg twice daily for 8 weeks might reduce some symptoms of depression and anxiety when compared with placebo (112141). However, the validity of these findings is limited by differences in baseline depression symptom scores between groups.
• Diabetes. It is unclear if oral rosemary is beneficial for improving glycemic control in patients with type 2 diabetes. Details: In patients with type 2 diabetes, preliminary clinical research shows that taking rosemary tea daily for 90 days decreases glycated hemoglobin levels by 15% and waist and hip circumference by 6% and improves insulin resistance. However, there was no effect on fasting blood glucose, lipid profile, body weight, or body mass index (BMI). The tea was made by adding rosemary 2 grams to a liter of boiling water for 3 minutes and then passing through a sieve (105323). Other preliminary clinical research in adults with type 2 diabetes shows that taking rosemary powder 3 grams daily for 4 weeks does not reduce fasting blood glucose levels or improve lipid profile when compared with baseline. These endpoints were improved in a group of healthy adults (105327). The validity of the findings from these studies is limited by the lack a comparator group.
• Diabetic nephropathy. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific combination product (Canephron N, Bionorica) containing 18 mg each of rosemary leaf, centaury herb, and lovage root per tablet, as two tablets three times daily for 6 months along with standard antidiabetes treatment and enalapril (Vasotec), decreases microalbuminuria by 73%, decreases albumin:creatinine ratio by 46%, increases high-density lipoprotein (HDL) cholesterol by 25%, and lowers triglyceride levels by 43%, but does not improve glomerular filtration rate, when compared to baseline. Improvements were greater in those taking the combination product than in those treated only with standard antidiabetes therapy and enalapril. However, the combination product does not appear to improve reductions in total cholesterol or low-density lipoprotein (LDL) cholesterol (91726).
• Dysmenorrhea. It is unclear if oral rosemary is beneficial for dysmenorrhea. Details: In patients with moderate primary dysmenorrhea, clinical research shows that taking rosemary extract 220 mg every 8 hours for the first three days of the menstrual cycle, repeated for two menstrual cycles, is as effective as mefenamic acid for reducing average pain and bleeding when compared with two baseline cycles (105328).
• Fatigue. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy young adults with below-average energy levels shows that taking a single dose of a mixture of rosemary from Albania (Rosmarinus officinalis) and Morocco (Rosmarinus eriocalyx) 1.7 grams does not consistently improve sustained attention, motivation to perform cognitive tasks, mental energy, or mental fatigue when compared with placebo (91731).
• Fibromyalgia. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with fibromyalgia shows that taking an oral product containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (Meta050, Metagenics), at a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks, does not improve symptoms when compared to baseline (18327).
• Gingivitis. A mouth rinse containing rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with mild to moderate gingivitis and mild plaque shows that rinsing the mouth with 10 mL of mouthwash containing 5% v/v of a combined alcoholic extract of rosemary, calendula, and ginger for 30 seconds twice daily after meals for 2 weeks decreases plaque formation, gingival inflammation, and gingival bleeding similarly to chlorhexidine gluconate 0.2% mouthwash and better than a placebo mouthwash (93555).
• Hypertension. Although there is interest in using oral rosemary for hypertension, there is insufficient reliable information about the clinical effects of rosemary for this condition.
• Hypotension. It is unclear if oral rosemary is beneficial for hypotension. Details: Preliminary clinical research in patients with primary hypotension shows that taking rosemary essential oil (Metapharmaceutical) 1 mL every 8 hours for 44 weeks increases systolic blood pressure by 13 mmHg and diastolic blood pressure by 7 mmHg when compared to baseline. However, blood pressure returned to near baseline values after treatment discontinuation (91730).
• Mental alertness. It is unclear if rosemary aromatherapy is beneficial for improving mental alertness. Details: Preliminary clinical research in nurses working on a night shift shows that placing one drop of rosemary oil on a surgical mask that is worn for 2 hours with a 10-minute on/15-minute off cycle modestly increases alertness and reduces sleepiness when compared with a water drop control (105324).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral rosemary leaf is beneficial in patients with NAFLD. Details: A small clinical study in patients with NAFLD shows that taking rosemary leaf powder 2 grams twice daily for 8 weeks, in conjunction with diet and exercise recommendations, does not improve measures of liver function, glycemic control, cholesterol, or body weight when compared with placebo (109561).
• Opioid withdrawal. It is unclear if oral rosemary is beneficial for opioid withdrawal when used in combination with methadone. Details: Preliminary clinical research shows that taking rosemary leaf along with methadone for 2 weeks improves symptoms of opioid withdrawal and the ability to sleep when compared with methadone alone after 3 and 7 days of treatment, but not after 2 weeks. Rosemary leaf was provided in capsules containing 300 mg each (Barij Essence Pharmaceutical Company) at a dose of 16 capsules daily for the first 3 days, 12 capsules daily for the next 4 days, and eight capsules daily for the next 7 days, in divided doses (91727).
• Osteoarthritis. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows subjective reductions in pain associated with osteoarthritis when oral formulations containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (NG440-2, Metagenics; Meta050, Metagenics) are used (18326,18327). The formulation used in one of these studies (Meta050, Metagenics) was taken in a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks (18327). The formulation used in the other study, which was taken daily for 4 weeks, contained rosemary leaf extract 112.5 mg, oleanolic acid from olive leaf 1 mg, and rho iso-alpha acids from hops 225 mg per tablet (18326).
• Raynaud syndrome. It is unclear if topical rosemary essential oil is beneficial in patients with Raynaud syndrome. Details: A very small, open-label study in patients with Raynaud syndrome caused by systemic scleroderma shows that applying 10 drops of rosemary 10% essential oil to the hands does not increase skin temperature or improve warmth perception when compared with olive oil (109560). However, this study may have been inadequately powered to detect a difference between groups.
• Rheumatoid arthritis (RA). Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows subjective decreases in pain associated with RA when oral formulations containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (NG440-2, Metagenics; Meta050, Metagenics) are used (18326,18327). The formulation used in one of these studies (Meta050, Metagenics) was taken in a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks (18327). The formulation used in the other study, which was taken daily for 4 weeks, contained rosemary leaf extract 112.5 mg, oleanolic acid from olive leaf 1 mg, and rho iso-alpha acids from hops 225 mg per tablet (18326).
• Stress. It is unclear if rosemary aromatherapy is beneficial for stress. Details: Preliminary clinical research on the use of rosemary aromatherapy for anxiety and stress is conflicting. In a group of graduate nursing students, perceived stress associated with taking a test was lower when inhalers containing rosemary or lavender oil were used. Three drops of rosemary essential oil were added to an inhaler and inhaled before and during the test. Pulse rates, but not blood pressure, were also reduced (18324). In contrast, a small clinical study in adults aged 18-30 years shows that the aroma from diluted rosemary essential oil applied to the wrist during timed crossword puzzle completion actually increases subjective feelings of anxiety and tension when compared with placebo (18325).
• Sunburn. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of rosemary and grapefruit extracts in a 1:1 ratio (NutroxSun, Monteloeder, Inc.), 250 mg orally once daily for 12 weeks, increases the amount of UV radiation needed to cause sunburn by 34% after 8 weeks and 56% after 12 weeks when compared to baseline (91728). The validity of these findings is limited by the lack of a comparator group.
• Upper respiratory tract infection (URTI). Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial among healthy adults shows that taking a combination product containing rosemary leaf extract, aloe gel powder, and poria mushroom extract daily for 8 weeks does not reduce the frequency, duration, or severity of URTI-related symptoms when compared with placebo. However, in patients receiving an influenza vaccine midway through the study, this product does seem to improve some immune response biomarkers when compared with placebo (111921). The amount of rosemary leaf extract in the supplement was not disclosed.
• Wound healing. It is unclear if topical rosemary cream is beneficial for wound healing. Details: A moderate-sized clinical trial among primiparous adults with medio-lateral episiotomy shows that applying a cream containing rosemary extract to the wound twice daily for 10 days improves episiotomy wound healing and reduces redness and discharge when compared with placebo cream (112143). More evidence is needed to rate rosemary for these uses.

(Read more about ROSEMARY)

LIKELY SAFE ...when consumed in amounts commonly found in foods. Hops extract and hops oil have Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when hops extract and hops-derived bitter acids are used orally and appropriately for medicinal purposes, short-term. Hops extract has been used with apparent safety in doses of up to 300 mg daily for 2-3 months. Hops-derived bitter acids have been used with apparent safety at a dose of 35 mg daily for 3 months (12,55338,55370,102899,105953,107813).

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

(Read more about HOPS)

LIKELY SAFE ...when olive fruit is used orally and appropriately in amounts commonly found in foods.

POSSIBLY SAFE ...when olive leaf extract is used orally and appropriately. Olive leaf extract providing 51-100 mg oleuropein daily has been used with apparent safety for 6-8 weeks (92245,92247,101860). There is insufficient reliable information available about the safety of olive fruit extract when used in amounts greater than those found in foods.

PREGNANCY AND LACTATION:
Insufficient reliable information available; stick with amounts commonly found in foods.

(Read more about OLIVE)

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

POSSIBLY SAFE ...when the leaf is used orally and appropriately in medicinal amounts (18). Powdered rosemary leaf has been used with apparent safety as a single dose of up to 1.5 grams (18246,91731) or at a dose of 1-4 grams daily for up to 8 weeks (91727,98536,105327,109561). ...when the essential oil is used topically and appropriately for up to 7 months (5177,91729,109560). ...when the essential oil is used by inhalation as aromatherapy, short-term (7107,18323,105324,109559).

LIKELY UNSAFE ...when the essential oil or very large quantities of rosemary leaf are used orally. Ingestion of undiluted rosemary oil or very large quantities of rosemary leaf can cause serious adverse effects (18,515).

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Rosemary might have uterine and menstrual flow stimulant effects (4,12,18), and might increase metabolism of estradiol and estrone (18331); avoid using. There is insufficient reliable information available about the safety of rosemary when used topically during pregnancy.

LACTATION:
There is insufficient reliable information available about the safety of using rosemary in medicinal amounts during lactation; avoid using.

(Read more about ROSEMARY)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of hops with sedative drugs might cause additive sedation.  Details Some animal research shows that hops has sedative effects (55415,55340,105930).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Hops extract does not seem to affect the metabolism of CYP1A2 substrates.  Details In vitro research suggests that flavonoid constituents of hops inhibit CYP1A2 enzyme activity (10686). However, a pharmacokinetic study in healthy postmenopausal patients shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, does not affect levels of caffeine, a CYP1A2 probe substrate (105954).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, hops extract might alter metabolism of CYP3A4 substrates; however, this effect may not be clinically significant.  Details Animal research suggests that specific constituents of hops, called lupulones, can induce hepatic CYP3A4 enzyme activity (55325). However, a pharmacokinetic study in healthy postmenopausal patients with normal metabolism shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, decreases the concentration of alprazolam, a CYP3A4 probe substrate, by 7.6%. This reduction is unlikely to be clinically relevant (105954).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of large amounts of hops might interfere with hormone replacement therapy due to competition for estrogen receptors.  Details In vitro research suggests that certain hops constituents can competitively bind to estrogen receptors (3701,10684,10685). However, most hops extracts contain very small amounts of these constituents (105930).

(Read more about HOPS)

(Read more about OLIVE)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro and animal research suggests that rosemary inhibits platelet aggregation (18334,18335,18336,18337).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking rosemary with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research shows that rosemary extract can decrease blood glucose levels in diabetic models (71821,71923). However, research in humans is conflicting. Although rosemary powder decreased blood glucose levels in healthy adults (105327), no change in blood glucose levels was seen in adults with type 2 diabetes, most of whom were taking antidiabetes drugs (105323,105327).

ASPIRIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as aspirin.  Details Rosemary is reported to contain salicylates (18330).

CHOLINE MAGNESIUM TRISALICYLATE (Trilisate) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as choline magnesium trisalicylate.  Details Rosemary is reported to contain salicylate (18330).

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, rosemary might decrease the levels and clinical effects of CYP1A1 substrates.  Details In vitro research shows that rosemary induces CYP1A1 enzymes (18332,18333). This effect has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, rosemary might decrease the levels and clinical effects of CYP1A2 substrates.  Details In vitro research shows that rosemary induces CYP1A2 enzymes (18332,18333). This effect has not been reported in humans.

SALSALATE (Disalcid) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as salsalate.  Details Rosemary is reported to contain salicylate (18330).

(Read more about ROSEMARY)

General ...Orally, hops extract and oil are generally well tolerated when used in food amounts. Hops extract also seems to be well tolerated when used in supplemental amounts.
Most Common Adverse Effects:
Orally: Drowsiness, sedation.

Dermatologic ...Topically, allergic reactions have been reported after contact with the fresh hops plant and plant dust. Contact dermatitis is attributed to the pollen (4,12,105930).

Genitourinary ...Orally, supplements containing hops and soy have been associated with 4 cases of postmenopausal bleeding (55404). It is unclear if this effect is due to hops, soy, or the combination. Also, menstrual disturbances have been reported in female workers harvesting hops (10684,55405).

Neurologic/CNS ...Orally, hops might cause drowsiness and sedation. Historically, hops are thought to have sedative effects, since workers harvesting hops were observed to tire easily after oral contact with hop resin. The European Medicines Agency states that hops may have sedative effects; however, there is a lack of clinical research confirming that hops extract causes drowsiness and sedation (105930).

Pulmonary/Respiratory ...Occupational exposure to dust from hops, usually in combination with dust from other products, is associated with chronic respiratory symptoms such as dry cough, dyspnea, chronic bronchitis, and other occupational respiratory diseases (55333,55414).

(Read more about HOPS)

General ...Orally, olive fruit is well tolerated when used in typical food amounts. Olive leaf extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Headache and stomach discomfort.

Dermatologic ...Orally, one patient in one clinical trial reported bad skin and acne after using olive leaf extract (101860).

Gastrointestinal ...Orally, three patients in one clinical trial reported stomach ache after using olive leaf extract (101860).

Neurologic/CNS ...Orally, three patients in one clinical trial reported headache after using olive leaf extract (101860).

Psychiatric ...In one case report, a 67-year-old female experienced irritability, anger, a lack of control, and feelings of sadness and negativity after consuming a multi-ingredient product containing olive leaf extract 5 grams, horseradish root, and eyebright daily for 38 days. All psychiatric symptoms disappeared within days of stopping the combined product. It is hypothesized that the hydroxytyrosol component of olive leaf extract contributed to these symptoms due to its chemical similarity to dopamine; however, it is not clear if these symptoms were due to the olive leaf extract or to the other ingredients (96245).

Pulmonary/Respiratory ...Olive tree pollen can cause seasonal respiratory allergy (1543).

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General ...Orally, rosemary seems to be well tolerated when used in appropriate medicinal amounts. Undiluted rosemary oil or very large quantities of rosemary leaf should not be consumed. Topically and as aromatherapy, rosemary seems to be well tolerated.

Dermatologic ...Topically, rosemary use can lead to photosensitivity, erythema, dermatitis, and cheilitis in hypersensitive individuals (4,6).

Immunologic ...Topically, allergic reactions can occur. When used in the mouth, lip and gum edema have occurred (101173). When used on the skin, allergic contact dermatitis has occurred, likely due to the constituent carnosol (71715,71924,71926).
Rosemary might also cause occupational asthma. A case of occupational asthma caused by several aromatic herbs including thyme, rosemary, bay leaf, and garlic has been reported. The diagnosis was confirmed by inhalation challenges. Although all of the herbs caused immediate skin reactivity, a radioallergosorbent test (RAST) showed that garlic was the most potent allergen by weight, with rosemary and the other herbs showing less reactivity (783).

Neurologic/CNS ...Orally, the undiluted oil, as well as the camphor constituent of rosemary, might cause seizures (4,5,6,12868).

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