Aller-Leaf [Discontinued] by Gaia Herbs SystemSupport

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral Baikal skullcap for allergic rhinitis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Anxiety. Although there has been interest in using oral Baikal skullcap for anxiety, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Atherosclerosis. Although there has been interest in using oral Baikal skullcap for atherosclerosis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral Baikal skullcap for ADHD, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Bronchiolitis. Intravenous Baikal skullcap has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that a combination of Baikal skullcap, forsythia, and honeysuckle, known as Shuang Huang Lian in traditional Chinese medicine, given intravenously, with or without antibiotics, decreases the duration of cough by about 1.5-2 days, the duration of wheezing by about 2 days, and the duration of hospitalization by about 2-3 days when compared with antibiotics alone in children with respiratory syncytial virus (RSV) infection. Baikal skullcap injection was administered as a 20 mL dose for patients under 6 months, a 40 mL dose for patients 7-36 months, or a 60 mL dose for patients older than 36 months (12613).
• Cancer. Although there has been interest in using oral Baikal skullcap for cancer, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Diabetes. It is unclear if oral Baikal skullcap is beneficial in patients with diabetes. Details: A very small clinical trial in patients with uncontrolled diabetes taking metformin 500 mg daily shows that taking Baikal skullcap extract 3.52 grams in three divided doses daily for 8 weeks does not decrease levels of fasting glucose or insulin or improve levels of glycated hemoglobin (HbA1c) when compared with placebo. However, taking Baikal skullcap reduces blood glucose levels during an oral glucose tolerance test (OGTT) at 60 minutes, but not 120 minutes, when compared with placebo (101738). This study may have been inadequately powered to detect a difference between groups.
• Epilepsy. Although there has been interest in using oral Baikal skullcap for epilepsy, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hand, foot, and mouth disease. It is unclear if intravenous Baikal skullcap is beneficial in patients with hand, foot, and mouth disease. Details: Low-quality observational research in children hospitalized with severe hand, foot, and mouth disease has found that children who are given Baikal skullcap intravenously as a Tanreqing injection 0.3-0.5 mL/kg once daily have a shorter duration of fever, oral ulcers, and rash, as well as reduced viral load, when compared with those given ribavirin 10 mg/kg once daily (96281). The validity of these findings is limited by the retrospective nature of the study.
• Headache. Although there has been interest in using oral Baikal skullcap for headache, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hemorrhoids. Although there has been interest in using oral Baikal skullcap for hemorrhoids, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hepatitis. Although there has been interest in using oral Baikal skullcap for hepatitis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• HIV/AIDS. Although there has been interest in using oral Baikal skullcap for HIV/AIDS, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Insomnia. Although there has been interest in using oral Baikal skullcap for insomnia, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Osteoarthritis. Oral Baikal skullcap 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 product (Limbrel, Primus Pharmaceuticals) that contains flavocoxid, a blend of Baikal skullcap extract and catechu flavonoid extract, 500 mg once or twice daily for up to 12 weeks reduces symptoms of osteoarthritis of the knee when compared with baseline. These studies found no significant difference between this combination product and naproxen 440 mg once daily to 500 mg twice daily for reducing symptoms (17030,18012,92776). However, in 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). See the Adverse Effects section for more information.
• Peyronie disease. It is unclear if oral Baikal skullcap is beneficial in patients with Peyronie disease. Details: Observational research has found that taking oral Baikal skullcap root extract 150 mL twice daily for 6 months is associated with reduced time to disease stabilization, with an average reduction of 5 months, when compared with no treatment. In addition, 17% of patients taking Baikal skullcap had pain resolution and only 33% required surgical correction, compared with 0% and 58%, respectively, of control patients. In patients requiring surgery, taking Baikal skullcap did not appear to affect resolution; however, the study may have been inadequately powered to detect a difference between groups (105867).
• Prostate cancer. Although there has been interest in using oral Baikal skullcap for prostate cancer, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Psoriasis. Although there has been interest in using oral Baikal skullcap for psoriasis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Seizures. Although there has been interest in using oral Baikal skullcap for seizures, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral and intravenous Baikal skullcap for upper respiratory tract infections, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose. More evidence is needed to rate Baikal skullcap for these uses.

(Read more about BAIKAL SKULLCAP)

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

(Read more about BAYBERRY)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral eyebright for allergic rhinitis, there is insufficient reliable information about the clinical effects of eyebright for this purpose.
• Asthenopia (eye strain). Although there has been interest in using topical eyebright for asthenopia, there is insufficient reliable information about the clinical effects of eyebright for this purpose.
• Blepharitis. Although there has been interest in using topical eyebright for blepharitis, there is insufficient reliable information about the clinical effects of eyebright for this purpose.
• Cancer. Although there has been interest in using oral eyebright for cancer, there is insufficient reliable information about the clinical effects of eyebright for this purpose.
• Common cold. Although there has been interest in using oral eyebright for the common cold, there is insufficient reliable information about the clinical effects of eyebright for this purpose.
• Conjunctivitis. It is unclear if topical eyebright eye drops are beneficial in patients with conjunctivitis. Details: A small observational study shows that applying one drop of eyebright eye drops (WALA Heilmittel GmbH, Eck-walden/Bad Boll) up to five times daily results in complete recovery in about 82% of patients with conjunctivitis after two weeks of treatment (49391). However, due to the lack of a comparator group, it is not clear if this improvement is due to eyebright or to the natural resolution of conjunctivitis symptoms.
• Cough. Although there has been interest in using oral eyebright for cough, there is insufficient reliable information about the clinical effects of eyebright for this purpose.
• Pharyngitis. Although there has been interest in using oral eyebright for pharyngitis, there is insufficient reliable information about the clinical effects of eyebright for this purpose.
• Rhinosinusitis. Although there has been interest in using oral eyebright for rhinosinusitis, there is insufficient reliable information about the clinical effects of eyebright for this purpose. More evidence is needed to rate eyebright for these uses.

(Read more about EYEBRIGHT)

POSSIBLY EFFECTIVE

• Migraine headache. Oral feverfew seems to reduce the frequency of migraines and improve migraine-related symptoms. Details: Most clinical research shows that taking feverfew can reduce the frequency of migraine headaches and reduce symptoms of pain, nausea, vomiting, and sensitivity to light and noise (5080,6959,6960,6961,12384,13239,19358,90607). It may be more effective in patients with more frequent migraine attacks (12384). Combination products containing feverfew and other ingredients have also been evaluated, with promising results in most studies (12389,19357,19359,22602,96531,96532,103009,107473). However, some conflicting evidence exists (727,6938,12153,12384). These conflicting findings may reflect differences in the harvested feverfew plants or differences in the bioavailability of commercially prepared feverfew products (12153). Dosing regimens with evidence of benefit include feverfew powder 50-150 mg once daily for up to 4 months (6959,6960,6961,90607) and a carbon dioxide extract of feverfew (MIG-99, Schaper & Brümmer GmbH & Co) 2.08-18.75 mg three times daily for 3 to 4 months (12384,13239).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Prurigo nodularis. It is unclear if topical feverfew is beneficial for patients with this skin condition. Details: Preliminary clinical research in people with prurigo nodularis shows that applying a topical cream containing feverfew (Aveeno Ultra-Calming Cream, Johnson & Johnson) modestly improves pruritus in about 90% of affected patients. However, the cream does not appear to cause complete remission of skin lesions (22601).
• Psoriasis. Although there has been interest in using oral feverfew for psoriasis, there is insufficient reliable information about the clinical effects of feverfew for this purpose.
• Rheumatoid arthritis (RA). It is unclear if oral feverfew is beneficial for patients with RA. Details: Preliminary clinical research in a small number of women with RA shows that taking dried chopped feverfew 70-86 mg daily for 6 weeks does not seem to reduce the symptoms of RA, including pain, stiffness, or grip strength, when compared with placebo (6933).
• Tension headache. Oral feverfew has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Observational research in children and adolescents with tension headache has found that taking a specific combination supplement (Partena) containing feverfew dry extract 150 mg (standardized to 1.2 mg of parthenolides), magnesium 169 mg, coenzyme Q10 20 mg, riboflavin 4.8 mg, and andrographis 100 mg twice daily for 4 weeks and then once daily for 12 weeks is associated with reduced headache frequency, but not pain intensity, when compared to baseline (103009). More evidence is needed to rate feverfew for these uses.

(Read more about FEVERFEW)

POSSIBLY INEFFECTIVE

• Urine drug tests. Drinking water with goldenseal or adding goldenseal tea to urine does not appear to cause a false negative urine drug screen for amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine, or tetrahydrocannabinol (THC). Details: Goldenseal is often promoted to mask illicit drugs in the urine, but drinking one gallon of water with goldenseal or adding goldenseal tea to urine samples does not seem to cause a false negative immunoassay (EMIT and TDx) for cocaine, amphetamines, barbiturates, benzodiazepines, or opiates. It also does not produce a false negative for Microgenics CEDIA DAU assays for amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine, or THC (260,261,52599). Although adding goldenseal tea to urine samples at 15 grams per liter may produce a false-negative EMIT reading for the presence of THC, the adulteration is obvious due to a brownish color in the urine (52599). Some people also claim that goldenseal can cause a false positive on a drug screen. However, goldenseal does not seem to cause false positives for the fluorescent polarization immunoassay (FPIA) or thin-layer chromatography (TLC) assays for amphetamines, opiates, cocaine, methadone, or their metabolites (2590).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using topical goldenseal for acne, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Allergic rhinitis (hay fever). Although there has been interest in using oral goldenseal for allergic rhinitis, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Anorexia nervosa. Although there has been interest in using oral goldenseal for anorexia nervosa, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Atopic dermatitis (eczema). Although there has been interest in using topical goldenseal for atopic dermatitis, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral goldenseal for CFS, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Conjunctivitis. Although there has been interest in using goldenseal as an eye drop for conjunctivitis, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Dandruff. Although there has been interest in using topical goldenseal for dandruff, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Flatulence. Although there has been interest in using oral goldenseal for flatulence, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Gastritis. Although there has been interest in using oral goldenseal for gastritis, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Gingivitis. Although there has been interest in using goldenseal as a mouthwash for gingivitis, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Hemorrhoids. Although there has been interest in using oral goldenseal for hemorrhoids, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Herpes labialis (cold sores). Although there has been interest in using topical goldenseal for herpes labialis, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Menorrhagia. Although there has been interest in using oral goldenseal for menorrhagia, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Otitis media. Although there has been interest in using goldenseal as an ear drop for otitis media, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Peptic ulcers. Although there has been interest in using oral goldenseal for peptic ulcers, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Respiratory tract infections. Although there has been interest in using oral goldenseal for various respiratory tract infections, including influenza, pneumonia, rhinosinusitis, and the common cold, there is insufficient reliable information about the clinical effects of goldenseal for these conditions.
• Tinnitus. Although there has been interest in using goldenseal as an ear drop for tinnitus, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Urinary tract infections (UTIs). Although there has been interest in using oral goldenseal for UTIs, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Uveitis. Although there has been interest in using goldenseal as an eye drop for uveitis, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Vaginitis. Although there has been interest in using oral goldenseal for vaginitis, there is insufficient reliable information about the clinical effects of goldenseal for this purpose.
• Wound healing. Although there has been interest in using topical goldenseal for wound healing, there is insufficient reliable information about the clinical effects of goldenseal for this purpose. There is insufficient reliable information available about the effectiveness of goldenseal for its other uses.

(Read more about GOLDENSEAL)

POSSIBLY EFFECTIVE

• Diabetes. Oral stinging nettle seems to improve glycemic control in patients with diabetes. Details: A meta-analysis of 8 small heterogeneous clinical trials in adults with type 2 diabetes shows that taking stinging nettle 1.5-10 grams in divided doses daily for 8-12 weeks reduces fasting blood glucose (FBG) by 18 mg/dL when compared with placebo (102865). Glycated hemoglobin (HbA1c) was not improved, but the study durations were not adequate to detect an improvement in this measure. Despite positive results on FBG, taking stinging nettle does not seem to improve insulin secretion or measures of insulin sensitivity (91519,102865,108903). Another meta-analysis of 3 small clinical studies in adults with type 2 diabetes shows that taking stinging nettle reduces HbA1c by about 1.3% when compared with placebo. This analysis also suggests stinging nettle reduces post-prandial blood glucose by about 114 mg/dL; however, this is based on a single study. Stinging nettle did not improve fasting blood glucose or insulin resistance in this analysis (111503). The validity of these findings is limited by the low quality and heterogeneity of included studies, as well as unclear dosing. Furthermore, since most research has been conducted in Iran, it is unknown if these findings are generalizable to other geographic locations. Stinging nettle has also been used in combination with other natural medicines. One small clinical study in adults with type 2 diabetes shows that taking a product containing stinging nettle leaf extract 200 mg, milk thistle 200 mg, and Boswellia serrata gum 200 mg three times daily for 3 months reduces FBP by about 28 mg/dL and HbA1c by about 1.5%, compared with a smaller reduction in the placebo group (96742). It is unclear if this effect is due to stinging nettle, the other ingredients, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral stinging nettle is beneficial for hay fever. Details: Taking stinging nettle leaf extract 300 mg 3-7 times daily at the first sign of hay fever symptoms seems to provide subjective improvement (7035). However, adding stinging nettle to conventional allergy medication might not provide any additional benefit. One small clinical study shows that adding stinging nettle tablets (Urtidin, Barij Essence Pharmaceutical Co.) 150 mg four times daily for 1 month to treatment with loratadine and nasal saline rinses does not improve symptoms of allergic rhinitis when compared with placebo with loratadine and nasal saline rinses (96743).
• Anemia. Although there is interest in using oral stinging nettle for anemia, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Asthma. Although there is interest in using oral stinging nettle for asthma, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Benign prostatic hyperplasia (BPH). It is unclear if oral stinging nettle is beneficial for BPH. Details: A meta-analysis of clinical research, including 5 clinical studies and 1,128 patients with BPH, shows that taking stinging nettle root extract 360-600 mg in divided doses daily for 2-12 months improves peak urinary flow rate and symptom scores while modestly reducing prostate volume when compared with control. However, the validity of these results is limited by significant heterogeneity due to the variability in the products used and the specific endpoints investigated (96744). In the largest clinical trial in the analysis, patients took stinging nettle root extract 120 mg three times daily for 6 months (76406). Stinging nettle has also been evaluated in combination products. Clinical research in patients with BPH shows that taking a specific combination product (PRO 160/120, Dr. Willmar Schwabe Pharmaceuticals) containing a specific extract of stinging nettle root (WS 1031) 120 mg plus a specific extract of saw palmetto fruit (WS 1473) 160 mg twice daily for 24-48 weeks seems to improve urinary tract symptoms when compared with control; the effect may last at least 48 weeks after treatment (15195,15551,76409). However, taking a different combination product does not seem to be beneficial. A small clinical study in patients with BPH shows that taking a product containing stinging nettle root extract 240 mg, saw palmetto, pumpkin seed oil, lemon bioflavonoid, and beta-carotene, three times daily for 6 months, does not improve symptoms of BPH (5093).
• Bleeding. Topical stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some preliminary clinical research shows that applying 4 mL of a specific product (Ankaferd blood stopper, Mefar Ilaç Sanayi A.S) containing alpinia, licorice, thyme, stinging nettle, and common grape vine to the affected area reduces bleeding, but does not improve the time for episiotomy repair, when compared with using saline (31010).
• Gingivitis. Stinging nettle in a mouthwash solution has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with moderate gingival inflammation suggests that using 10 mL of mouthwash solution containing a 1:1:1 mixture of stinging nettle, juniper, and yarrow twice daily for 3 months does not reduce plaque or bleeding when compared with control (76443). It is not clear if this effect is due to stinging nettle, the other ingredients, or the combination.
• Gout. Although there is interest in using oral stinging nettle for gout, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Gulf war syndrome. It is unclear if oral stinging nettle is beneficial for Gulf war syndrome. Details: A very small exploratory clinical trial in males with Gulf war syndrome shows that taking stinging nettle leaf (Nature's Way) 1305 mg in two divided doses daily for 30 days modestly improves symptom severity when compared with placebo (108311). The clinical relevance of this finding is limited by the use of an unvalidated scoring scale. Additionally, it appears that most patients had mild, unspecified symptoms at baseline; it is unclear if stinging nettle is beneficial for moderate to severe symptoms.
• Hyperandrogenism. It is unclear if oral stinging nettle is beneficial in patients with hyperandrogenism. Details: Preliminary clinical research in females with hyperandrogenism shows that taking dried extract of stinging nettle root 300-600 mg daily for approximately 4 months decreases total and free testosterone levels, but not menstrual cycle conditions, oily skin, or acne, when compared with taking spironolactone and cyproterone (91520).
• Insect bite. Oral stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a homeopathic after-bite gel, containing stinging nettle, Echinacea, and marsh Labrador tea, on affected areas does not reduce erythema or itching after a mosquito bite when compared with placebo (89235).
• Kidney stones (nephrolithiasis). Although there is interest in using oral stinging nettle for kidney stones, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Myalgia. Although there is interest in using topical stinging nettle for myalgia, there is insufficient reliable information about the clinical effects of stinging nettle for this purpose.
• Osteoarthritis. Small clinical studies suggest that topical stinging nettle may modestly improve pain in patients with osteoarthritis. It is unclear if oral stinging nettle is beneficial. Details: Topically, stinging nettle leaf may have a counterirritant effect which may improve osteoarthritis pain in some patients. A small clinical study in patients ages 45-82 with osteoarthritis of the thumb shows that applying raw stinging nettle leaf to the thumb for 30 seconds daily for 1 week reduces pain and disability when compared with white dead nettle leaf control (12490). However, in another small clinical study in patients with knee osteoarthritis, topical application of raw stinging nettle leaf to the knee for 1 minute daily for 7 days does not seem to be more effective for reducing pain than applying a leaf from a related stingless nettle (76412). Non-raw stinging nettle has also been tried. In a small open-label study, a formulation of stinging nettle extract (Liquid PhytoCaps Nettle Leaf, Gaia Herbs) 13.33% compounded with lipobase oil-in-water emulsion and applied to the affected area twice daily for 2 weeks, modestly improves pain and function in patients with radiologically confirmed osteoarthritis when compared with baseline (76414). The validity of this finding is limited by the lack of a comparator group. Stinging nettle has also been evaluated orally, in combination with other ingredients. A clinical study in adults with knee osteoarthritis shows that taking a specific combination solution (Rosaxan, medAgil Gesundheitsgesellschaft mbH) containing stinging nettle extract 160 mg, rose hip puree 20 grams, devil's claw 108 mg, and vitamin D 200 IU daily for 12 weeks improves symptoms by an additional 28% and pain scores by an additional 33% when compared with placebo (96741). It is unclear if this effect is due to stinging nettle, the other ingredients, or the combination.
• Tinnitus. Oral stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with tinnitus shows that taking a specific product containing stinging nettle, tansy, and rose hip (Neurotec, Rose Pharmed), 100 mg orally daily for 3 months does not improve auditory thresholds when compared with placebo. However, the product improved some subjective symptoms scores, such as perceived loudness and severity scores (110512).
• Urinary tract infections (UTIs). Although there is interest in using oral stinging nettle for UTIs, there is insufficient reliable information about the clinical effects of stinging nettle for this condition. More evidence is needed to rate stinging nettle for these uses.

(Read more about STINGING NETTLE)

POSSIBLY EFFECTIVE

• Allergic rhinitis (hay fever). Oral turmeric seems to improve symptoms in people with allergic rhinitis. Details: A large clinical study in people with allergic rhinitis shows that taking a specific curcumin product (Organika Health Products) 500 mg daily for 2 months reduces nasal symptoms, including sneezing, itching, runny nose, and congestion, when compared with placebo (96138).
• Depression. Most research shows that oral curcumin, a constituent of turmeric, when used at doses of at least 1 gram daily for at least 6 weeks improves symptoms of depression when taken alone or in combination with antidepressant medications. Details: Curcumin appears to be most beneficial for depression in middle aged patients compared to older patients, when taken for at least 6 weeks, and when used at a dose of at least 1 gram daily. In adults with major depressive disorder, a meta-analysis of data from 6 clinical studies, as well as individual studies not included in this analysis, show that taking curcumin 1 gram daily along with an antidepressant moderately improves depression symptoms when compared with placebo (96131,96139). Another meta-analysis of 10 studies shows symptom reductions in patients with major depression when combined with conventional antidepressants, but not when used alone in patients with milder depressive symptoms. However, the quality of the evidence is low (104971). Additionally, a large clinical study in adults with mild-moderate symptoms of depression shows that taking curcumin 750 mg twice daily for 12 months modestly reduces depression symptoms when compared with placebo (114898). When used alone, one clinical study shows that curcumin 1 gram daily for 6 weeks may be similarly effective to fluoxetine 20 mg daily. Taking both products together seems to be more effective than either product alone, increasing the response rate from 65% to 78% (89728). Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that curcumin extract at doses of 500-1000 mg daily is provisionally recommended for monotherapy or adjunctive use in mild to moderate depression (110318).
• Dyspepsia. Oral turmeric may be modestly beneficial for some patients with dyspepsia. In patients with functional dyspepsia, small clinical studies show that oral curcumin, a constituent of turmeric, is similarly effective when compared with the proton-pump inhibitor omeprazole. Details: Clinical research shows that taking turmeric 500 mg four times daily for 7 days can relieve overall symptoms of dyspepsia in 64% more patients than taking placebo (11144). A small, unblinded clinical study in patients with a type of dyspepsia called postprandial distress syndrome shows that taking turmeric 250 mg or 500 mg orally three times daily after meals for 4 weeks is associated with reductions in symptom scores which are similar to those seen with simethicone 60 mg three times daily for 4 weeks. However, the recurrence rate upon stopping therapy was about 14% with simethicone, compared with 43% to 46% with turmeric (104963). In patients with functional dyspepsia, taking the constituent curcumin appears similarly effective when compared with omeprazole, but might not provide further symptom reduction in those also taking famotidine or omeprazole (106063,106801,111599). One small clinical study in Iran shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily in addition to famotidine 40 mg daily for 30 days is no more effective for reducing overall symptoms of dyspepsia, such as abdominal pain, heartburn, bloating, and nausea, when compared with famotidine alone (106063). Another small clinical study in Thailand shows that taking curcumin 500 mg four times daily for 4 weeks is similarly effective for reducing dyspepsia severity and improving satisfaction when compared with an unspecified dose of omeprazole and more effective when compared with placebo (106801). Similarly, a moderate-size clinical study in Thailand shows that taking curcumin 500 mg four times daily for 4 weeks is similarly effective for reducing dyspepsia severity when compared with omeprazole 20 mg daily. However, taking curcumin and omeprazole in combination did not provide further symptom reduction (111599). The validity of these results is limited by the high rate of study dropouts.
• Hyperlipidemia. Research is conflicting on whether oral turmeric, curcumin, or curcuminoids can reduce serum lipids. Any improvement in lipids is likely to be small. Reasons for the conflicting findings may relate to turmeric formulation, duration of treatment, and/or the baseline cholesterol status of the included patients. Details: Results from meta-analyses of clinical research show inconsistent and conflicting results. One large meta-analysis of over 50 clinical studies in healthy adults and those with a variety of conditions shows that supplementation with turmeric or curcumin 80-4000 mg daily for 4-24 weeks reduces total cholesterol by 4 mg/dL, low-density lipoprotein (LDL) cholesterol by 5 mg/dL, and triglycerides by 7 mg/dL and increases high-density lipoprotein (HDL) cholesterol by 2 mg/dL when compared with placebo (112119). Two other meta-analyses of 27 clinical studies agree that taking turmeric, curcumin, or curcuminoids moderately reduce triglyceride levels but suggest that turmeric does not improve total cholesterol when compared with placebo. However, the meta-analyses contradict one another on whether turmeric and its constituents reduce LDL cholesterol or increase HDL cholesterol. (96128,96135). Additionally, a third meta-analysis of 10 clinical trials shows that taking up to 2400 mg daily of curcumin or curcuminoids, from turmeric or isolated sources, for up to 12 weeks, does not significantly improve triglycerides, LDL cholesterol, HDL cholesterol, or total cholesterol (110220).
• Nonalcoholic fatty liver disease (NAFLD). Oral curcumin, a constituent of turmeric, seems to attenuate fat deposition and improve some metabolic parameters in adults with NAFLD. Details: Clinical research shows that taking curcumin daily reduces NAFLD severity in 30% to 79% of patients, compared to 5% to 27.5% of patients receiving placebo. Curcumin also reduces the quantity of additional fat deposition in the liver to 0% to 4.5%, compared to 17.5% to 26% in those taking placebo. Most research shows that taking curcumin also reduces liver enzyme levels, body mass index (BMI), blood glucose levels, glycated hemoglobin (HbA1c), and total cholesterol when compared with placebo. Although some clinical research shows that taking curcumin improves levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, a meta-analysis of clinical research shows that these lipid levels are not improved in patients with NAFLD, specifically (97430,97431,100258,102350,106062,107120,109279,111349,114901). However, another meta-analysis of 14 small, heterogeneous clinical studies in adults with NAFLD, that included some of these studies, shows that taking various doses and forms of turmeric or curcumin modestly reduces liver enzyme levels, improves measures of insulin resistance, reduces waist circumference, and improves LDL, HDL, and triglyceride levels when compared with placebo (111348). A small clinical trial in patients with NAFLD given specific lifestyle recommendations shows that taking curcumin modestly reduces the frequency of metabolic syndrome and fatty liver but does not have beneficial effects on fatty liver-associated indices, adiposity, or the atherogenic index, when compared with placebo (109285). Findings for specific endpoints are mixed between individual studies and may depend on the dose and formulation of curcumin used or the duration of treatment. These studies have used various doses and formulations. In one study, 500 mg of a dispersion formulation equivalent to 70 mg of curcumin daily for 8 weeks was used (97430). Also, 250 mg once daily or 500 mg twice daily of a specific phytosomal formulation (Meriva, Indena) containing curcumin and soy phosphatidylcholine in a 1:2 ratio and standardized to an overall curcuminoid content of 20% was taken for 8 weeks (97431,106062). Another study used 1 gram of powdered turmeric rhizome taken three times daily with meals for 12 weeks (102350). One study used a curcumin-piperine complex (Curcumin C3 complex 500 mg plus Bioperine 5 mg) daily for 8 weeks (107120). One study used curcumin (Arjuna Natural Extract) 500 mg three times daily for 12 weeks (109285). Despite positive results with curcumin in several small clinical studies of patients with NAFLD, there is some concern that curcumin might cause hepatotoxicity in rare cases, especially when highly bioavailable formulations are used in high doses (103633). There is also evidence that the risk for hepatotoxicity with curcumin may be increased in individuals with the HLAB*35:01 allele (109288). Curcumin-induced hepatotoxicity has not been reported in clinical trials of patients with NAFLD, and its potential mechanism is unclear. However, patients seeking to take curcumin for NAFLD should be advised to monitor for symptoms of hepatotoxicity, including abdominal pain, dark urine, fatigue, jaundice, nausea, and pruritus.
• Oral mucositis. Oral curcumin or curcumin-containing mouthwash seem to reduce the development of severe oral mucositis, as well as reduce the severity and pain of oral mucositis, associated with cancer treatment. Details: Clinical research in patients receiving radiotherapy following recent radical surgery for oral cancer shows that taking turmeric (BCM-95, Arjuna Natural Pvt. Ltd., India) during radiotherapy reduces the incidence of severe oral mucositis to 25% or 20% in those taking turmeric 500 mg two or three times daily, respectively, compared with 65% in those taking placebo. The incidences of severe oral pain, dysphagia, and dermatitis were also reduced by at least 50% (105398). A small clinical study in patients receiving chemotherapy with or without head and neck radiotherapy shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 7 weeks improves severity of oral mucositis at weeks 1, 4, and 7 and reduces pain at week 7 when compared with placebo. Effects were more pronounced in those with chemotherapy-induced oral mucositis than radiotherapy-induced oral mucositis (106800). In patients with head and neck cancer receiving radiotherapy, preliminary clinical research shows that swishing with 10 mL of turmeric solution (prepared by dissolving turmeric 400 mg in 80 mL of water) six times daily for 6 weeks delays mucositis and reduces the number of cases of intolerable mucositis by 49% when compared to swishing with 10 mL of povidone-iodine solution twice daily for 6 weeks (89726). Another small clinical study shows that swishing with 10 mL of nanoparticulate curcumin 0.1% mouthwash three times daily for 6 weeks is associated with a 50% lower risk of developing oral mucositis, and a delay of 2 weeks in the onset of mucositis, when compared with benzydamine 0.15% mouthwash (104969). A small clinical study in patients with mucositis due to head and neck radiotherapy shows that taking curcumin nanoparticles (SinaCurcumin, ExirNanoSina) 40 mg daily or using 10 mL of a curcumin 0.1% mouthwash three times daily for up to 21 days improves scores related to pain, burning, ulceration, and erythema when compared with placebo. Results with either oral or topical curcumin were similar (111350).
• Osteoarthritis. Some oral turmeric extracts and combination products containing turmeric seem to improve certain symptoms of knee osteoarthritis. However, it is unclear how turmeric compares to the use of non-steroidal anti-inflammatory drugs (NSAIDs). Details: Several meta-analyses of clinical studies show that turmeric extracts and/or curcuminoid products reduce knee pain and stiffness, improve physical function, and reduce the need for rescue medication when compared with placebo (104970,106792,109280,110222). However, a reduced effect was noted in patients with increasing age or body mass index (104790). The studies evaluated in these meta-analyses are heterogeneous, of low- to moderate-quality, and utilized a variety of products and/or dosing strategies (104970,106792,109280,110222). Small to moderate-sized clinical studies show that specific products (Meriva, Indena; Theracurmin, Theravalues Corp) containing curcumin 90-100 mg twice daily for up to 6 months, or specific turmeric extracts (Turmacin, Natural Remedies Pvt. Ltd.; Curcugen, DolCas Biotech, LLC) 500 mg twice daily for 6-12 weeks, reduce pain and analgesic use and improve functionality when compared with placebo (17953,80988,89721,97424,104148,107118). A specific turmeric extract (CuraMed, EuroPharma USA) 1500 mg daily for 12 weeks improves functionality, but not pain, when compared with placebo (96127). Also, a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina), 40 mg twice daily for 6 weeks, improves pain, stiffness, and physical activity scores and reduces intake of rescue acetaminophen by about 60% when compared with placebo (102349). However, not all turmeric products seem to be effective for improving symptoms of osteoarthritis. One small clinical study shows that taking a specific turmeric extract (B-Turmactive, PLAMECA S.A.) 500 mg daily for one week does not reduce knee pain when compared with placebo (104147). Also, a meta-analysis of clinical research shows that benefits are limited to bio-optimized forms of curcuminoids, and benefits related to pure extracts are lacking (110222). Turmeric has also been compared with conventional treatments for knee osteoarthritis in small meta-analyses, a network meta-analysis, and individual clinical studies. However, the evidence is mixed as to whether turmeric is as effective or more effective than NSAIDs, such as ibuprofen 400 mg taken 2-3 times daily, diclofenac 25-100 mg daily, or chondroprotective drugs (17952,89720,89722,106792,109280,110222,113607). A network meta-analysis comparing 6 interventions in adults with knee osteoarthritis suggests that curcumin monotherapy, curcumin with chondroprotective agents, or curcumin with NSAIDs improves scores related to pain, function, and stiffness while reducing the need for rescue medication and the incidence of adverse events (113607). Individual studies are heterogenous with respect to comparator medication and dosing schedule. Doses included a non-commercial turmeric extract 500 mg 3-4 times daily for 4-6 weeks (17952,89720) or turmeric extract 500 mg twice daily for 3 months (89722). Topical turmeric has also been evaluated. One clinical study shows that applying curcumin topically as a 5% ointment in Vaseline twice daily for 6 weeks reduces pain associated with knee osteoarthritis by a mean of about 11 on a 100-point visual analog scale when compared with placebo (104964). Another clinical study in patients with knee osteoarthritis shows that applying curcumin in a self-nano-emulsifying polyethylene glycol organogel 1.5 grams to the knee twice daily for 8 weeks reduces pain, stiffness, and difficulty with physical function scores by 72%, 62%, and 46%, respectively, when compared to baseline, with improvements superior to placebo for all outcomes (113357). Research also shows that taking specific combination products containing turmeric and other ingredients can improve pain and functionality in patients with osteoarthritis. These combination products have combined turmeric with chondroitin sulfate and glucosamine hydrochloride (CartiJoint Forte, Fidia Farmaceutici SpA); boswellic acid (Curamin, EuroPharma USA; Rhulief); Boswellia serrata (Rhulief); ashwagandha, Boswellia serrata, and zinc (Articulin-F, Eisen Pharmaceutical Co. Pvt. Ltd.); devil's claw and bromelain (AINAT, Laboratoire de Rhumatologie Appliquée); Boswellia serrata, guggul, and valerian (Phytoproflex, OPTM Healthcare); Boswellia serrata and terminalia (LI73014F2, Laila Nutraceuticals); ashwagandha, Boswellia serrata, and ginger (Artrex, Mendar); or extracts of ginger rhizome, devil's claw tuber, Boswellia serrata resin, and celery seed (Tregocel, Max Biocare) (19276,51950,81466,89717,89719,96127,97419,97421,97428,106078)(109280).
• Pruritus. Oral turmeric has been evaluated for the management of pruritus of various etiologies, with promising results. Details: Clinical research in patients with kidney failure shows that taking turmeric 500 mg orally three times daily for 8 weeks decreases symptoms of uremic pruritus by 1.9-fold when compared with placebo (89724). Also, a small clinical study in patients with sulfur mustard-induced chronic pruritus shows that taking a specific combination product (C3 Complex, Sami Labs LTD) containing curcumin 1 gram plus extract from black pepper or long pepper (Bioperine) daily for 4 weeks reduces pruritus severity and improves quality of life when compared with placebo (81120,81176).

POSSIBLY INEFFECTIVE

• Alzheimer disease. Neither oral turmeric nor its constituent curcumin appears to improve cognitive function or attenuate cognitive decline in adults with this condition. Details: A small clinical trial shows that taking the turmeric constituent, curcumin, 1-4 grams daily for 6 months does not improve mental state examination scores when compared with placebo (17096). Furthermore, a meta-analysis of this study and another small clinical study in patients with Alzheimer disease shows that the turmeric group experienced greater cognitive decline when compared with placebo (100261). While this research is limited by small study sizes and heterogeneous patient populations, the current evidence does not support the use of turmeric in patients with this condition.
• Peptic ulcers. Oral turmeric does not seem to improve the healing of peptic or gastric ulcers when compared with placebo or liquid antacids. Details: Some clinical research shows that taking turmeric 2 grams three times daily for 8 weeks does not improve the healing of peptic ulcers when compared with placebo in Vietnamese patients (81444). Also, taking powdered turmeric rhizome 250 mg four times daily for 6 weeks seems to be less effective than a liquid aluminum-magnesium-hydroxide antacid for promoting gastric ulcer healing (81284).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using topical turmeric for acne, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Age-related cognitive decline. Some small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve cognition in elderly patients experiencing cognitive decline. Details: A meta-analysis of three small clinical trials shows that curcumin modestly improves cognition in the elderly (100261). One of these clinical trials shows that taking a specific brand of curcumin (Theracurmin, Theravalues Corp.) 90 mg twice daily for 18 months improves long-term memory and attention when compared with placebo in middle-aged and older adults with or without mild cognitive impairment (96161).
• Amenorrhea. Although there has been interest in using oral turmeric for amenorrhea, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Ankylosing spondylitis. Although there has been interest in using oral turmeric for ankylosing spondylitis, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Anxiety. Some clinical research show that oral curcumin reduces symptoms of anxiety. Details: A meta-analysis of 8 mostly low-quality clinical studies in adults with anxiety symptoms or an anxiety disorder diagnosis shows that taking curcumin 500-1000 mg daily for up to 12 weeks modestly reduces symptoms of anxiety when compared with placebo (114902). The validity of the meta-analysis is limited by the heterogeneity of the included studies, including differences in the patient populations, form and doses curcumin, treatment durations, and types of anxiety scales used. Additionally, all studies were conducted in either Iran or Australia which may limit generalizability of results to other populations.
• Aromatase inhibitor-induced arthralgia. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for aromatase inhibitor-induced arthralgia. Details: A small clinical trial in patients experiencing aromatase inhibitor-induced arthralgia shows that taking curcuminoids as a nanoemulsion (Curcumin C3 Complex, Sabinsa Corporation) 200 mg daily for 3 months does not improve grip strength or joint symptoms when compared with placebo (113345). However, this study may have been underpowered to detect a difference between groups.
• Asthma. Some small clinical studies suggest that oral turmeric, as an adjunct to conventional asthma treatment, does not improve lung function or symptoms in adults and children with asthma. Details: One small clinical study in adults with mild to moderate asthma shows that adjuvant therapy with turmeric as curcumin 500 mg twice daily for 30 days does not improve lung function based on FEV1, or improve symptoms such as dyspnea, wheezing, cough, or tightness, when compared to standard treatment alone (99349). A small clinical trial in children 7-18 years of age with moderate to severe asthma shows that adding turmeric 500-1000 mg (containing 20-40 mg curcuminoids) daily for 6 months to standard therapy does not improve overall asthma symptoms when compared with placebo and standard therapy, although it may decrease the frequency of nighttime awakenings and the use of rescue inhalers (99348). Due to their small sizes and high drop-out rates, these studies may have been underpowered to detect a difference between groups.
• Athletic performance. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for athletic performance. Details: Preliminary clinical research in middle-aged male long-distance runners shows that taking a turmeric extract providing 2 grams of curcumin 95% and piperine 5% daily for 6 weeks does not improve aerobic capacity when compared with placebo (109286).
• Benign prostatic hyperplasia (BPH). It is unclear if oral curcumin, a constituent of turmeric, is beneficial in BPH. Details: A clinical study in patients with BPH shows that taking curcumin 2250 mg once daily along with tamsulosin and finasteride for 6 months improves lower urinary tract symptoms related to storage, but not overall symptoms or symptoms related to voiding, by about 35%, compared with 25% in those receiving tamsulosin and finasteride alone. Periprostatic fat thickness, quality of life, and erectile function also were improved (106799).
• Beta-thalassemia. It is unclear if oral turmeric is beneficial for iron overload in patients with beta-thalassemia. Details: A small clinical study in patients with beta-thalassemia major and iron overload shows that taking turmeric extract containing curcumin 500 mg twice daily for 12 weeks modestly reduces non-transferrin bound iron (NTBI) by 0.6 micromol/L, but not hemoglobin, transferrin saturation, total iron binding capacity, ferritin, or hepcidin, when compared with placebo (99306). Another small clinical study in adult males with beta-thalassemia intermedia and iron overload shows that taking a higher dose of curcumin 500 mg three times daily for 12 weeks modestly reduces serum iron and ferritin turmeric levels and transferrin saturation when compared with placebo (108871).
• Bruises. Although there has been interest in using topical turmeric to alleviate bruising, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Cachexia. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for cancer cachexia. Details: A small clinical trial in patients with cancer anorexia-cachexia syndrome shows that taking curcumin 800 mg twice daily for 8 weeks does not reduce weight loss or improve body composition or handgrip strength when compared with placebo (109283).
• Canker sores. Some preliminary research suggests that topical curcumin, a constituent of turmeric, is beneficial for minor canker sores. Details: Preliminary clinical research in young adults with minor canker sores shows that applying a 2% curcumin oral gel for 6 months reduces ulcer size, pain, and recurrence rate and increases healing rate similarly to 0.1% triamcinolone oral paste (104962). The validity of the study is limited by a lack of investigator blinding and the lack of an intention to treat analysis. Another small clinical study shows that applying a 1% curcumin nanomicelle gel (SinaCurcumin Pharmaceuticals) on lesions three times daily for one week is modestly more effective than applying a 2% curcumin gel for reducing pain and ulcer size (109282). The validity of this finding is limited by the lack of a non-curcumin comparator group.
• Carpal tunnel syndrome. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. It is unclear if topical curcumin, a constituent of turmeric, is beneficial for carpal tunnel syndrome. Details: A moderate-sized clinical study in adults with mild to moderate carpal tunnel syndrome shows that taking a combination product containing turmeric, alpha-lipoic acid, acetyl-L-carnitine, phosphatidylserine, and vitamins C, E, B1, B2, B6, and B12 twice daily for 60 days reduces symptom severity and pain but does not improve measures of hand and wrist function when compared with control (111702). The validity of these effects is limited by a lack of blinding. The study may also be inadequately powered to detect a difference between groups. Additionally, it is unclear if the effects are due to turmeric, other ingredients, or the combination. Topical turmeric has also been investigated. A small clinical study in patients with mild to moderate carpal tunnel syndrome shows that applying a 1% curcuminoid gel (Sinanomin) to the wrists twice daily for 8 weeks modestly decreases symptom severity and improves function when compared with a placebo gel. However, there was no change in electrodiagnostic testing of the injury. All patients also used a night splint (113356).
• Chemotherapy-induced acral erythema. It is unclear if oral or topical turmeric reduces the risk for acral erythema from capecitabine. Details: A small clinical trial in adults with cancer shows that taking turmeric 4 grams daily for 6 weeks starting at the beginning of treatment with capecitabine does not reduce the incidence of acral erythema overall; however, it does seem to reduce acral erythema grade 2 or higher when compared with expected incidence rates (99309). Topical turmeric has also been evaluated. A clinical study in patients with colorectal, gastric, pancreatic, or breast cancer receiving capecitabine shows that applying a specific ointment (Alpha) standardized to contain curcumin extract 0.5% and henna extract 10% to the soles and palms twice daily, beginning on day 1 of chemotherapy and continued for 4 cycles, does not prevent acral erythema or improve World Health Organization severity scores when compared with placebo. A post-hoc analysis suggests that there may have been a trend toward delayed onset and progression; however, this study was not structured to assess these outcomes (108874).
• Chemotherapy-induced constipation. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced constipation. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks does not reduce symptoms of constipation when compared with placebo (107111).
• Chemotherapy-induced diarrhea. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced diarrhea. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks does not reduce symptoms of diarrhea when compared with placebo (107111).
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if oral curcumin reduces CINV. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks modestly reduces symptoms of nausea, but not vomiting, in the second and third months after the start of treatment when compared with placebo (107111).
• Chemotherapy-induced peripheral neuropathy. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced peripheral neuropathy. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks modestly reduces symptoms of chemotherapy-induced peripheral neuropathy over a three-month period when compared with placebo (107111).
• Chronic kidney disease (CKD). It is unclear if oral turmeric is beneficial for CKD. Details: A meta-analysis of four small clinical trials in patients with CKD related to diabetic nephropathy or lupus nephritis shows that taking curcumin or turmeric for 0.5-4 months moderately reduces proteinuria when compared with placebo (109276). Also, a small clinical trial in children and young adults ages 6-25 years with vascular dysfunction related to autosomal dominant polycystic disease (PKD) shows that curcumin powder 25 mg/kg daily for 12 months does not improve vascular function or kidney function when compared with placebo (107117).
• Colorectal adenoma. It is unclear if oral turmeric is beneficial for managing colorectal adenoma. Details: Preliminary clinical research in adults with familial adenomatous polyposis shows that taking curcumin 1500 mg twice daily for 12 months does not reduce the quantity or size of lower intestinal adenomatous polyps when compared with placebo (97427). A very small clinical trial in patients with familial adenomatous polyposis shows that taking 8 capsules daily of a turmeric extract, in a formulation also containing pepper fruit, spirulina, seaweed, and ginger root, for 6 months does not affect total polyp number or burden when compared with placebo. However, both number and burden were modestly reduced in the left colon. Each capsule provided curcuminoids 123.65 mg and turmerones 26.79 mg (110223).
• Colorectal cancer. It is unclear if oral turmeric is beneficial for the prevention or treatment of colorectal cancer. Details: A small clinical trial in patients undergoing chemotherapy following colorectal cancer surgery shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily for 8 weeks modestly improves some measures of quality of life when compared with placebo (107109). In addition, a small clinical study in people at high risk for colorectal cancer, such as those who smoke, shows that taking the turmeric constituent, curcumin, 4 grams daily for 30 days can reduce the number of precancerous rectal aberrant crypt foci (18204). It is not clear if this results in a reduced risk for colorectal cancer.
• Coronary artery bypass graft (CABG) surgery. One small study suggests that oral turmeric may reduce the risk for myocardial infarction after CABG surgery. Details: Preliminary clinical research shows that taking the turmeric constituent, curcuminoids, 4 grams daily in four divided doses, beginning 3 days prior to surgery and continuing for 5 days post-surgery, decreases the relative risk of myocardial infarction following CABG by approximately 56% when compared with placebo (81143).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral turmeric or its constituent, curcumin, is beneficial for reducing symptoms of COVID-19. Details: Small studies have evaluated curcumin as an adjunctive therapy in adults hospitalized with confirmed COVID-19. Patients in these studies also received treatments such as antimicrobials, anti-inflammatory medications, anticoagulants, antiretrovirals, and immunosuppressants (104966,105393,107119). One study shows that adding curcumin reduces the duration of shortness of breath by 6-9 days when compared with patients who received other treatments in combination with probiotics. However, there were no differences in the duration of other symptoms, including fever, cough, or sore throat. Subgroup analyses suggest that taking curcumin may improve oxygenation and reduce the need for supplemental oxygen or ventilation (105393). Another study shows that adding curcumin modestly reduces the time to resolution of COVID-19 symptoms, the length of supplemental oxygen use, and the likelihood for deterioration in the patients' condition when compared with patients who received other treatments alone (104966). A third study shows some benefit of curcumin on fever and cough when compared with baseline; however, it is unclear if any changes were significant when compared with placebo (107119). Doses of curcumin used in these studies include curcumin 525 mg with piperine 2.5 mg (C3 Complex, SamiDirect) twice daily, starting at admission and continuing for 14 days (105393), or a specific nanocurcumin product (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 2 weeks or 240 mg daily in divided doses for 7 days (104966,107119). Limitations of these studies include the small number of patients with severe symptoms, the large number of outcomes evaluated, the inconsistencies in other treatments used, the lack of clarity related to presentation of some results, and, in most cases, a lack of blinding. Turmeric has also been evaluated in adults in the outpatient setting with suspected or confirmed mild to moderate COVID-19. One small clinical study shows that taking curcumin (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 14 days in addition to other COVID-19 treatments (mainly hydroxychloroquine and azithromycin) reduces the duration of cough, chills, myalgia, and smell and taste disturbance, but not dyspnea, fever, sore throat, or others, by 1-2 days when compared with placebo with other treatments (106802). The validity of this study is limited by the lack of confirmatory diagnosis at baseline and lack of consistency with other treatments, as well as the unclear reporting of symptom duration in relation to the initiation of treatment. Another small clinical study in outpatients confirmed to have COVID-19 shows that taking curcumin 1000 mg plus piperine 10 mg (Sami Labs Limited) daily for 14 days modestly improves weakness, but not cough, pain, headache, difficulty breathing, or biochemical indices, when compared with placebo (109278). However, a clinical study in adults with confirmed asymptomatic or mild COVID-19 shows that taking curcumin (curcuRouge®, TheraBioPharma) 360 mg twice daily for 7 days within 5 days of COVID-19 diagnosis does not reduce the risk of fever or oxygen saturation below 96% when compared with placebo (114905). Some research has also examined the effect of turmeric as part of a polyherbal combination. Clinical research in patients hospitalized for moderate COVID-19 symptoms shows that using an Ayurvedic formulation 1776 mg twice daily containing turmeric, ashwagandha, ginger, and Boswellia serrata (BV-4051) for 14 days modestly reduces the duration of illness and reduces the severity of fever, cough, and smell and taste dysfunction when compared to placebo. There was no beneficial effect on other symptoms, including nasal congestion, breathing difficulty, headache, and gastrointestinal symptoms. More than half of the patients were also treated with remdesivir which did not impact the majority of these findings (109899).
• Crohn disease. It is unclear if oral turmeric is beneficial for improving symptoms of active Crohn disease. Details: Some clinical research shows that taking the turmeric constituent, curcumin, 1.08 grams daily for one month, then 1.44 grams daily for one month, can reduce bowel movements, diarrhea, and abdominal pain when compared to baseline in patients with Crohn disease (79730). The validity of these findings is limited by the lack of a comparator group.
• Denture stomatitis. Topical turmeric may be beneficial for treating denture stomatitis. Details: A small clinical study in patients with denture stomatitis shows that applying topical curcumin gel (Curenext, Abbott Laboratories) three times daily for 2 weeks resolves denture stomatitis lesions similarly to clotrimazole ointment (106797).
• Diabetes. Lower quality clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve glycemic control in patients with diabetes. Details: A meta-analysis of small clinical trials in patients with diabetic kidney disease shows that curcumin reduces levels of fasting glucose by approximately 8.3 mg/dL when compared with placebo. Curcumin was used in doses of 66.3-1670 mg daily for 2-6 months (107114). Preliminary clinical research included in the analysis shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 12 weeks reduces fasting blood glucose by about 20 mg/dL (104149). Other meta-analyses of low- to moderate-quality clinical studies in patients with a variety of conditions including type 2 diabetes show that taking turmeric extract, curcumin, or curcuminoids for 4-36 weeks improves glycated hemoglobin (HbA1c) by 0.4-0.7% and reduces fasting glucose by approximately 13 mg/dL when compared with placebo or conventional treatment (106806,108877,113604). The validity of these findings is limited by the heterogeneity of the included studies and broad curcuminoid doses ranging from 46-1500 mg daily. Conversely, other meta-analyses in patients with type 2 diabetes show that curcumin does not reduce HbA1c or insulin levels when compared with placebo (104965,108877,113604).
• Diabetic foot ulcers. It is unclear if oral curcumin is beneficial in patients with diabetic foot ulcers. Details: Preliminary clinical research in patients with grade 3 diabetic foot ulcers shows that taking nanocurcumin 80 mg orally daily for 12 weeks does not improve glycated hemoglobin (HbA1c) or change the rate of ulcer healing when compared with placebo. Taking turmeric did result in modest decreases in fasting blood glucose, insulin levels, and insulin resistance (104972).
• Diabetic nephropathy. It is unclear if oral curcumin is beneficial in patients with diabetic nephropathy. Details: Meta-analyses of two to four small clinical trials in patients with diabetic kidney disease show that curcumin modestly improves serum levels of creatinine, total cholesterol, and fasting glucose, and reduces systolic blood pressure by 4 mmHg, when compared with placebo. However, there was no effect on diastolic blood pressure, proteinuria, or serum levels of other plasma lipids or blood urea nitrogen. Curcumin was used in doses of 66.3-1670 mg daily for 2-6 months (107114). One small study included in this analysis, which evaluated patients receiving hemodialysis, shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 12 weeks reduces fasting blood glucose by about 20 mg/dL when compared with placebo (104149).
• Dysmenorrhea. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in university students aged 18 to 24 in Iran with mild to severe primary dysmenorrhea and premenstrual syndrome (PMS) shows that taking a specific combination product containing curcumin 500 mg plus extract from black pepper 5 mg (C3 Complex, Sami Labs) daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation for 3 consecutive menstrual cycles, does not improve the severity of symptoms when compared with placebo (106805). Conversely, a small clinical study in adults with moderately painful dysmenorrhea shows that taking a single dose of a combination product containing turmeric, Boswellia serrata, and sesame (Rhuleave-K, Arjuna Natural Private Ltd.) 1000 mg at the start of menstruation relieves menstrual cramp pain and reduces pain intensity for up to 6 hours when compared with placebo (112806). However, it is unclear if these effects are due to turmeric, other ingredients, or the combinations.
• Endometriosis. It is unclear if oral turmeric is beneficial for reducing pain due to endometriosis. Details: A small clinical study in adults with endometriosis shows that taking the turmeric constituent, curcumin, 500 mg twice daily for 8 weeks does not affect pain associated with endometriosis or quality of life when compared with placebo (113603).
• Erythema. Although there has been interest in using topical turmeric for reducing erythema, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
• Exercise-induced muscle damage. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for reducing muscle damage from exercise. Details: A meta-analysis of 12 small, lower-quality clinical studies in adults shows that taking curcumin 150-500 mg as a single dose before or after exercise or 180-5000 mg daily for up to 56 days reduces markers of muscle damage (i.e. serum creatine kinase levels) when compared with placebo. Curcumin seems most beneficial for this effect in untrained adults and when administered as a single dose. Additionally, a meta-analysis of 3 of these clinical studies shows that curcumin improves range of motion (114897). The interpretation of these findings is limited by significant heterogeneity.
• Exercise-induced muscle soreness. It is unclear if oral turmeric or its constituent, curcumin, is beneficial for reducing muscle soreness from exercise. Details: A meta-analysis of 12 small, lower-quality clinical studies in trained and untrained adults shows that taking curcumin 150-500 mg as a single dose before or after exercise or 180-5000 mg daily for up to 56 days time reduces muscle soreness when compared with placebo. Subgroup analysis indicated that the largest effect size is observed at 96 hours post-exercise with progressively smaller effect sizes at earlier time points (114897). The interpretation of these findings is limited by significant heterogeneity. Turmeric has also been examined in combination with other ingredients. Clinical research in healthy active adults with moderate to severe exercise-induced muscle pain shows that taking a single, 1000-mg dose of turmeric and Boswellia serrata extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) improves pain relief when compared with placebo, with maximal benefits within about 3 hours. The number of people needed to treat to obtain pain relief of at least 50% over a 6-hour period was 1.1 (109277).
• Gingivitis. Small clinical studies suggest that oral turmeric and turmeric mouthwash may reduce the severity of gingivitis. Turmeric mouthwash appears to be similarly effective to chlorhexidine mouthwash. Details: A meta-analysis of generally preliminary clinical research shows that rinsing with a mouthwash containing curcumin for 3-4 weeks is as effective as rinsing with chlorhexidine for reducing the severity of gingivitis or plaque (106059). Mouthwashes in these studies contained 0.05% to 20% curcumin and were usually used twice daily for 3-4 weeks (81127,89723,106059). One mouthwash contained 0.05% turmeric extract and 0.005% eugenol (89723). Another small clinical trial shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily by mouth after breakfast for 4 weeks reduces the severity of gingivitis and gingival bleeding, but not plaque, when compared with placebo in patients with gingivitis and mild periodontitis (104146).
• Gout. Although there is interest in using oral turmeric for gout, there is insufficient reliable information about the clinical effects of turmeric for this condition.
• Gulf war syndrome. It is unclear if oral curcumin is beneficial in patients with Gulf war syndrome. Details: A small preliminary clinical trial in patients with Gulf war syndrome shows that taking curcumin (Meriva, Indena, S.p.A.) 500 mg twice daily for 30 days reduces overall symptoms, including pain, fatigue, gastrointestinal distress, and others, by 19% when compared with baseline. Taking a higher dose of 2000 mg twice daily for an additional 30 days appears to be no more effective than the lower dose (105395).
• Hearing loss. It is unclear if oral turmeric is beneficial for treating hearing loss. Details: A small clinical study in adults with mild to moderate hearing impairment shows that taking curcumin 500 mg daily for 12 weeks improves some measures of auditory function, such as auditory brain stem response threshold, when compared with placebo (114906).
• Helicobacter pylori. Small clinical studies suggest that oral turmeric is not beneficial for eradicating H. pylori when used alone or in combination with standard triple therapy or famotidine. Details: One small clinical study in patients with H. pylori gastritis shows that taking turmeric 2.1 grams daily for 4 weeks is less effective for eradicating H. pylori than taking an omeprazole-based triple regimen for one week (80957). Another small study in adults with peptic ulcers shows that taking a specific curcumin product (C3 Complex, Sami Labs LTD) 500 mg daily for 7 days, in conjunction with standard triple therapy, does not improve H. pylori eradication rates when compared with standard triple therapy alone. The addition of curcumin increased the resolution of dyspepsia symptoms by an additional 21%, but the clinical significance of this outcome is unclear (97420). In patients with dyspepsia, most of whom tested positive for fecal H. pylori antigen, clinical research shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily in addition to famotidine 40 mg daily for 30 days is no more effective for reducing fecal H. pylori antigen levels than taking famotidine alone (106063).
• Hypertension. It is unclear if oral curcumin is beneficial in patients with hypertension. Details: A meta-analysis of approximately 30 clinical studies in healthy adults or patients with a variety of conditions shows that taking turmeric, curcumin, curcuminoids, or nano-curcumin for 4 to 24 weeks reduces systolic blood pressure by about 2 mmHg and diastolic blood pressure by about 0.8 mmHg when compared with placebo (113602). However, these blood pressure reductions may not be clinically meaningful. In addition, most of the included studies were small and utilized heterogeneous dosing regimens.
• Impaired glucose tolerance (prediabetes). Oral turmeric may modestly improve glucose control in some patients with prediabetes. Details: In overweight or obese individuals with prediabetes, clinical research shows that taking a turmeric extract (BCM95 or Cucugreen; M/s Arjuna Natural Pvt Ltd.) 500 mg daily, providing 95% curcuminoids and at least 65% curcumin, for 90 days, either alone or in combination with zinc 30 mg as zinc gluconate, results in a small reduction in fasting glucose and glycated hemoglobin (HbA1c) when compared with placebo. There was also a small benefit in insulin sensitivity (105391). Other preliminary clinical research in adults with prediabetes shows that taking 500 mg of a combination of turmeric extract and Indian gooseberry extract in a 1:2 ratio along with phosphatidylcholine (EmbliQur) twice daily for 6 months modestly reduces fasting glucose and improves insulin resistance, when compared with placebo. However, changes in most other endpoints were not significantly different from placebo. Each 500 mg capsule contained turmeric extracts 29.86% and turmeric oil 1.27% (113355). The effect of turmeric on progression to type 2 diabetes in patients with prediabetes has also been investigated. Preliminary clinical research shows that taking a turmeric extract containing curcumin 750 mg twice daily for 9 months reduces the percentage of patients with prediabetes who develop type 2 diabetes when compared with placebo (81163).
• Irritable bowel syndrome (IBS). It is unclear if oral turmeric is beneficial for improving symptoms of IBS. Details: Preliminary clinical research in otherwise healthy adults with IBS shows that taking a turmeric extract (Cynara Turmeric, Lichtwer Pharma) 72-144 mg daily for 8 weeks reduces IBS symptoms by about 40% to 60% when compared to baseline (79565). The validity of this finding is limited by the lack of a comparator group. Taking a combination product (CU-FEO, Alfa Wasserman S.p.A.) containing curcumin 42 mg and fennel essential oil 25 mg per capsule twice daily for 60 days improves overall ratings of abdominal pain, abdominal distention, and quality of life by 24% when compared with placebo (97422). It is unclear if these effects are due to turmeric, fennel, or the combination. Observational research suggests that adding a supplement (Enterofytol PLUS) providing curcumin 42 mg and berberine 200 mg twice daily for 2 months to conventional IBS treatment is associated with improvements in symptoms, such as abdominal discomfort, distension, and stool status, by up to 48% when compared with conventional treatment alone. Use of the supplement was also associated with a 64% reduced need for conventional treatments (113354).
• Joint pain. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking capsules of a specific combination product (Instaflex Joint Support, Direct Digital) containing glucosamine sulfate 1500 mg, methylsulfonylmethane 500 mg, white willow bark extract 250 mg, ginger root concentrate 50 mg, Boswellia extract 125 mg, turmeric root extract 50 mg, cayenne 40 m H.U. 50 mg, and hyaluronic acid 4 mg in three divided doses daily for 8 weeks reduces joint pain severity by 37% compared to only 16% with placebo. However, it does not improve joint stiffness or function when compared with placebo (89560). It is unclear if these effects are due to turmeric, other ingredients, or the combination.
• Juvenile idiopathic arthritis (JIA). Although there is interest in using oral turmeric for JIA, there is insufficient reliable information about the clinical effects of turmeric for this condition.
• Knee pain. It is unclear if oral turmeric is beneficial for knee pain. Details: Clinical research in individuals with knee pain not related to existing arthritis shows that taking turmeric extract (TurmXTRA 60N; Inventia Healthcare Ltd. and Laila Nutraceuticals) 250 mg, providing 60% curcuminoids, once daily for 90 days modestly reduces pain associated with walking 80 meters when compared with placebo. The time taken to walk 80 meters and to climb nine steps was reduced by 4-5 seconds (105396).
• Lichen planus. Evidence is conflicting on whether turmeric is beneficial for lichen planus. Details: A meta-analysis of several small, heterogeneous, mostly low-quality clinical and observational studies in adults with oral lichen planus shows that oral or topical curcumin with or without corticosteroids for 2-12 weeks does not improve erythema, lesion size, or pain when compared with control (113605). Similarly, a network meta-analysis of small clinical trials in patients with oral lichen planus shows that applying topical turmeric gel does not improve symptoms, clinical resolution, clinical scores, or reduce pain when compared with other available interventions (111640). However, small individual clinical studies have shown some benefit in using turmeric for lichen planus. A small clinical study shows that taking a specific turmeric extract (Curcumin C3 Complex, Sabinsa Corporation) containing curcuminoids 6000 mg daily in three divided doses for 12 days can reduce erythema and ulceration associated with lichen planus when compared with placebo (81109). Another small clinical study shows that taking a nanocurcumin product (SinaCurcumin, ExirNanoSina) 80 mg orally once daily for 1 month reduces oral lichen planus lesion size, pain, and burning similarly to prednisolone 10 mg taken orally once daily for 1 month (104961).
• Metabolic syndrome. It is unclear if oral turmeric is beneficial for metabolic syndrome. Details: Research is conflicting on how turmeric, curcumin, and other formulations affect various measures of metabolic syndrome. Some clinical research and a meta-analysis of 13 clinical studies in patients with metabolic syndrome show that taking turmeric or curcumin decreases low-density lipoprotein (LDL) cholesterol, waist circumference by 2 cm, fasting blood glucose by 9 mg/dL, and diastolic blood pressure by 3 mmHg and increases high-density lipoprotein (HDL) cholesterol by 5 mg/dL when compared with placebo. However, other research shows that turmeric or curcumin have no effect on body weight, lipids, blood pressure, or blood glucose when compared with placebo (98999,99311,105400,109284,111347,112118). The validity of these effects is limited by high heterogeneity within the included studies and incomplete information about randomization and blinding. Studies have used turmeric, curcumin, and curcumin extract 80-2400 mg, in divided doses, daily for 4-12 weeks, nano-curcumin 80 mg daily for 12 weeks, or calebin A (CurCousin, Sabinsa), which is a constituent of turmeric, 25 mg twice daily for 3 months (98999,99311,105400,109284,111347,112118). Also, taking crude or phosphorylated curcuminoids 1 gram daily for 6 weeks does not improve sleep or reduce weight in these patients (105397).
• Migraine headache. It is unclear if oral curcumin is beneficial for migraine headache. Details: A small clinical trial in females with regular migraines shows that taking curcumin 500 mg twice daily for 8 weeks reduces the severity and duration, but not the frequency, of migraine headaches when compared with placebo. In individuals taking curcumin, the duration of headache per month was reduced by approximately 10.3 hours from baseline (107116).
• Myocardial infarction (MI). It is unclear if oral curcumin is beneficial for reducing myocardial injury following a MI. Details: Clinical research in patients with an acute MI shows that taking curcuminoids 500 mg plus piperine (Bioperine) 5 mg daily (Sami Labs) for 8 weeks does not improve ejection fraction, serum levels of cardiac troponin 1, blood pressure, levels of fasting blood glucose, or kidney function parameters when compared to placebo. However, there were some modest benefits on levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, glycated hemoglobin, and certain liver enzymes such as aspartate aminotransferase (AST) and alkaline phosphatase (ALP) (107115). The validity of this study is limited by its short duration and relatively small sample size.
• Obesity. Oral turmeric might modestly improve weight loss, although any effect is unlikely to be clinically significant. Details: Multiple meta-analyses of small, mostly low-quality clinical studies in adults with a variety of comorbid conditions show that taking various forms and doses of turmeric or curcumin results in an average weight loss of about 0.6-1 kg, a decrease in body mass index (BMI) of about 0.2-0.5 kg/m2, and a decrease in waist circumference of about 1.3 cm when compared with control (102345,111351,111352). A sub-analysis of dose and duration shows that a reduction in waist circumference only occurs with curcumin daily doses above 1000 mg, and duration of treatment longer than 8 weeks (102345).
• Oral submucous fibrosis. Small studies suggest that topical or oral curcumin might be beneficial for oral submucous fibrosis. However, the research is heterogenous with respect to outcomes, comparators, and the turmeric preparations, doses, and routes of administration utilized. Details: A meta-analysis of 3 small clinical trials shows that turmeric modestly improves mouth opening when compared with control. In addition, a systematic review of 11 studies shows that turmeric improves overall symptoms, including mouth opening, tongue protrusion, burning sensation, and cheek flexibility. However, studies were small with short duration and used variable dosing strategies. Most trials have studied oral turmeric 300-400 mg, either alone or with black pepper 100 mg or piperine 5 mg, for 3-6 months. Less commonly, turmeric was provided in lozenge form (105399). Also, a network meta-analysis suggests that the turmeric constituent curcumin with or without piperine is most the effective for reducing tongue protrusion when compared indirectly with various medical and antioxidant therapies; however, this analysis suggests that curcumin does not rank among the most effective interventions for improving mouth opening, burning sensation, or cheek flexibility (113514). Other preliminary clinical research shows that taking a specific oral product containing curcumin 300 mg and piperine 5 mg (Turmix tablets, Sanat Products), three times daily for 12 weeks, improves mouth opening, burning sensation, and tongue protrusion when compared with baseline, but not when compared with an antioxidant product containing alpha-lipoic acid, beta-carotene, copper, lycopene, selenium, and zinc. Mouth opening is further improved by concurrent use of a mouthwash (Turmix mouthwash, Sanat Products), containing 0.1% w/v turmeric extract (standardized to 95% curcumin), with thymol, eucalyptol, clove oil, mentha oil, and tea tree oil, twice daily for 12 weeks (102347). A small clinical study shows that applying topical curcumin gel (Curenext, Abbott Laboratories) 5 mg daily in 3-4 divided doses for 6 weeks, in combination with oral physical therapy, improves mouth opening similarly to using an aloe vera gel in combination with oral physical therapy. However, decreases in burning sensation are greater with aloe gel than curcumin gel (104967). It is not clear whether the gels, oral physical therapy, or the combination of both is responsible for the outcome. Finally, clinical research shows that applying a paste providing turmeric and holy basil 10 grams each, mixed in 10 mL of honey, to the oral mucosa 4 times daily for 3 months modestly improves mouth opening, tongue protrusion, and burning sensation and reduces the presence of fibrous bands when compared with taking a vitamin B supplement. There was no effect on the shape of the uvula (113325).
• Pain (acute). Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with acute musculoskeletal pain shows that taking a specific combination product containing turmeric and Boswellia serrata extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) 1000 mg daily for 7 days is as effective as acetaminophen 1000 mg daily for pain relief, onset of pain relief, and onset of maximal pain relief (109287). This study is limited by its lack of blinding and placebo control. Additionally, the dose of acetaminophen used in this study is below the standard recommended daily dose.
• Periodontitis. There is limited evidence on the oral or topical use of turmeric or its constituent curcumin in patients with periodontitis. Details: A meta-analysis of heterogenous clinical studies in patients with chronic periodontitis suggests that use of local delivery gel products, usually turmeric 2% or a specific product containing curcumin (Curenext), modestly reduces pocket depth when compared with routine products, such as chlorhexidine. However, limited research suggests that curcumin products do not affect plaque or gingivitis measures, and curcumin irrigation does not affect pocket depth based on limited research (107108). A small preliminary clinical study in patients with severe chronic periodontitis shows that placing curcumin gel 2 mg on one side of the mouth along with scaling and root planing (SRP) reduces plaque and probing pocket depth, but not gingival index, when compared with SRP alone (101339). The use of oral curcumin has also been investigated. A small clinical trial in patients with gingivitis and mild periodontitis shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily after breakfast for 4 weeks reduces the severity of gingivitis and gingival bleeding, but not plaque, when compared with placebo (104146).
• Physical performance. It is unclear if oral turmeric may be beneficial for improving physical performance in older adults. Details: A very small clinical study in moderately functioning, sedentary adults over age 65 with low-grade chronic inflammation shows that that taking a specific turmeric extract (Curcumin C3 Complex, Sabinsa Corporation) 500 mg twice daily for 12 weeks does not improve measures of physical function, walking speed, or muscle strength when compared with placebo (111357). However, this study may have been inadequately powered to detect any possible differences between groups.
• Polycystic ovary syndrome (PCOS). Small clinical studies suggest that oral curcumin may improve some metabolic parameters in patients with PCOS, but these improvements may not be considered clinically significant. Details: Clinical research in patients with PCOS shows that taking curcumin 500 mg one to three times daily for 6-12 weeks improves some metabolic parameters (104968,105394,106795). Conversely, a small clinical study in patients aged 18 to 45 with PCOS in Iran shows that taking curcumin 1000 mg daily for 12 weeks modestly reduces fasting glucose but does not improve other metabolic parameters when compared with placebo. Taking curcumin also did not improve testosterone levels or hirsutism scores (111355). Meta-analyses show that taking curcumin modestly decreases body mass index (BMI) and improves measures of glycemic control, including fasting glucose and insulin resistance, and levels of total cholesterol when compared with placebo or metformin alone. However, effects on high-density lipoprotein (HDL) cholesterol levels were mixed and there was no effect on low-density lipoprotein (LDL) cholesterol or triglyceride levels (105394,106795,110219). Other preliminary clinical research shows that taking curcumin decreases plasma dehydroepiandrosterone and fasting plasma glucose levels when compared with placebo (104968). Some clinical research also shows that taking nano-curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 3 months is beneficial in patients already taking metformin 1500 mg daily. Taking curcumin had modest beneficial effects on fasting insulin and insulin resistance, as well as levels of testosterone, LDL cholesterol, HDL cholesterol, and triglycerides, when compared with metformin alone. There was no effect of curcumin on body weight, fasting blood glucose, or other hormones (106060).
• Postoperative pain. Small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly reduce pain in various postoperative recovery settings. Details: One small clinical study in patients undergoing laparoscopic cholecystectomy shows that taking curcumin 2 grams daily reduces postoperative pain, fatigue, and the need for analgesics by the second postoperative week when compared with placebo (81099). In patients undergoing surgery for inguinal hernia and/or hydrocele, taking curcumin 1.2 grams daily for 5 days reduces inflammation and tenderness by the sixth postoperative day when compared with placebo (81206). Curcumin was taken in 3-4 divided doses daily in these studies. Finally, taking a single dose of curcumin 200 mg after surgical removal of impacted third molars modestly reduces acute postoperative pain when compared with taking mefenamic acid 500 mg (99305).
• Premenstrual syndrome (PMS). It is unclear if oral turmeric may be beneficial for improving symptoms of PMS. Details: Some preliminary clinical research in patients with PMS shows that taking curcumin 100 mg twice daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation, improves physical, behavioral, and mood symptoms, as well as overall severity of symptoms, when compared with placebo (97433). Conversely, in university students aged 18 to 24 in Iran with mild to severe PMS and primary dysmenorrhea, a clinical study shows that taking a specific combination product containing curcumin 500 mg plus extract from black pepper 5 mg (C3 Complex, Sami Labs) daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation for 3 consecutive menstrual cycles, does not improve the severity of symptoms when compared with placebo (106805).
• Prostate cancer. It is unclear if oral turmeric is beneficial for the prevention or treatment of prostate cancer. Details: One small clinical study shows that taking curcumin 1.8 grams orally three times daily for 7 days, starting 4 days prior to docetaxel and prednisone treatment and continuing for up to 6 cycles, reduces PSA levels by at least half in 59% of patients when compared to baseline. Also, all patients with measurable lesions showed at least stable disease after treatment, and 40% of patients showed partial response when compared with baseline (96132). It is unclear if the addition of turmeric is beneficial when compared with docetaxel and prednisone alone. In contrast, an additional small clinical trial shows that taking curcumin 6 grams daily for 7 days every 3 weeks, starting four days before docetaxel, does not improve PSA levels or progression-free or overall survival when compared with docetaxel alone (105392).
• Psoriasis. Evidence is limited to one small study of topical use in patients with scalp psoriasis. Details: Preliminary clinical research in adults with scalp psoriasis shows that applying a tonic of turmeric to the scalp twice daily for 9 weeks modestly improves overall symptoms and quality of life when compared with a placebo tonic (97429).
• Quality of life. Some preliminary clinical research suggests that oral curcumin might improve quality of life in patients with various chronic conditions. Details: Small or low-quality clinical trials in various patient populations show that taking curcumin improves at least some measures of quality of life when compared with placebo. Research has been conducted in patients with cancer, sulfur mustard-induced chronic pruritus, benign prostatic hyperplasia (BPH), or irritable bowel syndrome (IBS). Studies have evaluated curcumin 2250 mg once daily for 6 months, a specific combination product (C3 Complex, Sami Labs LTD) containing curcumin 500-1000 mg plus piperine (Bioperine) daily for 4-9 weeks, or a combination product (CU-FEO, Alfa Wasserman S.p.A.) containing curcumin 42 mg and fennel essential oil 25 mg per capsule twice daily for 60 days (81120,81176,97422,106799,107109,107111). Also, in patients with scalp psoriasis, applying a tonic of turmeric to the scalp twice daily for 9 weeks modestly improves quality of life when compared with a placebo tonic (97429).
• Radiation dermatitis. It is unclear if oral or topical turmeric is beneficial for reducing the severity of radiation dermatitis. Details: A meta-analysis of 4 clinical studies in patients with breast cancer shows that taking curcumin 500-2000 mg three times daily for 3-7 weeks or applying curcumin gel 500 mg three times daily for 7 weeks reduces the radiation dermatitis severity score by about 0.5 points (on a 4-point scale) when compared with placebo or other control (111354). The validity of this analysis is limited by the heterogeneity of the included studies. However, a small clinical study in patients with breast cancer shows that taking nanocurcumin 80 mg twice daily during and for up to 2 weeks after treatment does not reduce skin reaction severity overall, but does modestly reduce pain, when compared with taking placebo. Also, there was a small reduction in skin reaction severity near the end of the study. All patients also used aloe vera leaf as part of the hospital protocol (109281). Another small preliminary clinical study in head and neck cancer patients shows that a specific cream (Vicco turmeric cream, Vicco Laboratories) containing turmeric and sandalwood oil, applied 5 times daily during radiation therapy, seems to reduce frequency and severity of radiation dermatitis when compared with baby oil (99307).
• Radiation proctopathy. It is unclear if oral turmeric is beneficial for preventing proctitis or cystitis in patients receiving radiotherapy for prostate cancer. Details: A small clinical study in patients with prostate cancer shows that taking a specific nanocurcumin product (SinaCurcumin, ExirNanoSina) 120 mg daily, for 3 days before and also during a course of radiotherapy, does not reduce the occurrence of proctitis or cystitis when compared with placebo (100259). This study may have been underpowered to detect small treatment effects.
• Respiratory tract infections. Although there is interest in using oral turmeric for various respiratory tract infections, including bronchitis and the common cold, it has not been clinically evaluated.
• Rheumatoid arthritis (RA). Small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve some symptoms of RA. Details: Meta-analyses of small clinical trials in patients with RA show that taking curcumin alone or with other treatments modestly reduces overall RA symptoms, pain, and markers of inflammation when compared with control groups, including placebo or other treatments. However, some research shows that there is no beneficial effect on tender or swollen joint count from the limited available clinical research (109280,111358), while other research shows that there is a benefit (112117). Clinical studies have evaluated curcumin 120-1200 mg daily for 2 weeks to 3 months (11149,18205,96129). The validity of these findings is limited by the small size of the studies, and in some cases, the lack of a comparator group.
• Sarcopenia. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in elderly patients with sarcopenia shows that taking a specific slow-release product containing turmeric, protein, carbohydrate, and fiber (Cureit, Aurea Biolabs), 500 mg orally daily for 3 months, increases handgrip strength by about 1% and distance walked before feeling tired by about 6% when compared with placebo. It also increases weightlifting capacity by about 6% from baseline, compared with a 5% decrease from baseline in those taking placebo (104973). It is unclear whether these small changes are clinically meaningful.
• Schizophrenia. Although there is interest in using oral turmeric for improving cognitive function in patients with schizophrenia, there is insufficient reliable information about the clinical effects of turmeric for this use.
• Sepsis. It is unclear if oral curcumin, a constituent of turmeric, is beneficial in patients with sepsis. Details: A small clinical trial in patients admitted to the intensive care unit (ICU) with sepsis shows that a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina), 80 mg dissolved in water and administered via gastric tube following lavage twice daily for 10 days does not affect length of ICU stay, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, blood pressure, or heart rate when compared with placebo (108873).
• Smoking cessation. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing turmeric 50 mg, ashwagandha, Indian gooseberry, tribulus, bacopa, Albizia lebbeck, licorice, clove, ginger, cowhage, and holy basil (Smotect, Smotect India) daily for 3 months reduces the number of cigarettes smoked by approximately 3 per day when compared with placebo. This product also reduces levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity (112115). However, only data from patients who completed treatment were analyzed, which limits the validity of this study. It is unclear if these effects are due to turmeric, other ingredients, or the combination. A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing turmeric 100 mg, ashwagandha, Indian gooseberry, tribulus, bacopa, Albizia lebbeck, licorice, clove, ginger, cowhage, and holy basil (Smotect, Smotect India) twice daily for 3 months reduces the number of cigarettes smoked by approximately 3 per day when compared with placebo. This product also reduces levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity (112115). However, only data from patients who completed treatment were analyzed, which limits the validity of this study. It is unclear if these effects are due to turmeric, other ingredients, or the combination.
• Stress. It is unclear if oral turmeric is beneficial for reducing occupational stress in healthy adults. Details: A small clinical trial in healthy adults with occupational stress-related anxiety and fatigue shows that taking a specific type of turmeric (CurQfen, Akay Flavours and Aromatics Pvt Ltd.) that contains fenugreek dietary fiber for improved bioavailability at a dose of 500 mg twice daily for 30 days reduces stress and fatigue and improves quality of life when compared with placebo, and also when compared with a standard curcumin supplement with lower bioavailability (99308).
• Stroke. It is unclear if oral turmeric is beneficial for stroke. Details: A small clinical study conducted in Iran in adults with a recent ischemic stroke shows that taking curcumin 500 mg and piperine, a pepper constituent, 5 mg (Sami Lans, India) daily for 12 weeks reduces carotid intima-media thickness, triglycerides, total cholesterol, and systolic and diastolic blood pressure, but does not improve low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or quality-of-life indicators when compared with placebo (113601). The validity of this study is limited by the lack of statistical adjustment for multiple comparisons which can lead studies to erroneously show differences between treatment groups.
• Systemic lupus erythematosus (SLE). There is limited evidence on the oral use of turmeric in adults with lupus nephritis. Details: Preliminary clinical research in adults with lupus nephritis shows that taking turmeric 1.5 grams daily in three divided doses for 3 months reduces systolic blood pressure and improves kidney function when compared to baseline (81104). The validity of this finding is limited by the lack of a comparator group.
• Tuberculosis. It is unclear if oral turmeric is beneficial in patients receiving treatment for tuberculosis. Details: A small clinical study in adults receiving antituberculosis treatment shows that taking a formulation containing turmeric 0.5 grams and Tinospora cordifolia 0.5 grams twice daily for 4 months can reduce levels of Mycobacterium tuberculosis in the sputum and improve lesion healing when compared with antituberculosis treatment alone. Also, liver toxicity associated with the antituberculosis treatment seems to be reduced when administered with this formulation (80424). It is unclear if these effects are due to turmeric, Tinospora cordifolia, or the combination.
• Ulcerative colitis. It is unclear if oral or rectal turmeric, or its constituent, curcumin, is beneficial in adults with ulcerative colitis. Details: Although two small clinical studies in adults with ulcerative colitis show that taking oral turmeric extract 2-3 grams daily for 1-6 months improves the rate of remission and reduces relapse rate (79966,97423), a meta-analysis of these studies and one additional clinical study shows that turmeric does not improve remission rates when compared with placebo (99000). A specific product (Cur-Cure, Bara Herbs Inc) was used in some of these studies. Reasons for the conflicting findings are unclear, but may be due to small patient populations, concerns about blinding, and the inclusion of patients who were also taking immunomodulating drugs. It may also be due to differences in how a study measures remission. A meta-analysis of small clinical studies in patients with mild to moderate ulcerative colitis shows that adding oral curcumin 0.5-3 grams daily to standard treatment for 1-6 months may improve clinical remission rates, but not endoscopic remission rates, when compared with placebo (108872). However, the validity of this finding is limited by the small number of studies that evaluated endoscopic remission. A small clinical study shows that administering an enema form of turmeric extract (NCB-02, Himalaya Drug Company) as 20 mL, containing turmeric extract 140 mg, daily for 8 weeks increases response rate from 50% to about 93% and increases remission rate from about 31% to 71% when compared with placebo in patients with active ulcerative colitis. However, patients using the turmeric extract enema for shorter durations did not improve when compared with placebo (89729). Turmeric has also been investigated in combination with the Mediterranean diet. A small clinical trial shows that taking curcumin (VeNatura Curcumin Supplement) 800 mg twice daily while following the Mediterranean diet for 8 weeks is no more effective for improving ulcerative colitis symptom severity than following the Mediterranean diet without supplemental curcumin (113339).
• Uveitis. It is unclear if oral curcumin is beneficial for uveitis. Details: Observational research in patients with acute non-infectious uveitic macular edema shows that taking a specific hydrophilic curcumin product (Cucrcuwin, Diabec, Alfa Intes) 60 mg twice daily for 6 months, in conjunction with standard corticosteroid treatment, and then alone for an additional 6 months, modestly improves best corrected visual acuity, but not macular thickness or intraocular pressure, when compared with standard treatment alone for 6 months (107110).
• Wound healing. Although there is interest in using topical turmeric for wound healing, there is insufficient reliable information about the clinical effects of turmeric for this condition. More evidence is needed to rate turmeric for these uses.

(Read more about TURMERIC)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). Although there is interest in using topical yarrow for atopic dermatitis, there is insufficient reliable information about the clinical effects of yarrow for this condition.
• Dysmenorrhea. It is unclear of oral yarrow tea is beneficial for improving symptoms of dysmenorrhea. Details: Preliminary clinical research in patients with moderate to severe dysmenorrhea shows that drinking a tea made with yarrow 4 grams three times daily for the first three days of two menstrual cycles modestly reduces dysmenorrhea pain when compared with a placebo tea (105361).
• Gingivitis. A mouthwash containing yarrow has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that using a mouthwash containing a combination of yarrow, juniper, and stinging nettle for 3 months does not improve dental plaque or gingivitis in patients with gingival inflammation when compared with a control group (76443).
• Irritable bowel syndrome (IBS). Oral yarrow has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with mild to moderate IBS shows that taking a capsule containing yarrow, ginger, and Boswellia serrata three times daily for 30 days improves pain by 46% and gastrointestinal symptoms by 60% when compared with placebo. Patients also experienced an improvement in overall mood when compared with placebo (96673). It is not clear if these effects are due to yarrow, the other ingredients, or the combination.
• Multiple sclerosis (MS). It is unclear if oral yarrow is beneficial for patients with MS. Details: A small clinical study in adults with relapsing-remitting MS shows that taking yarrow whole plant extract 250 mg or 500 mg daily in conjunction with conventional treatments for 12 months reduces the annual relapse rate and increases time to first relapse when compared with placebo. Taking yarrow 500 mg daily also reduced disability scores and improved functional scores when compared with either yarrow 250 mg daily or placebo (100346). However, most of the patients enrolled in the study were under 40 years of age, with undefined disease severity.
• Nipple fissures. It is unclear if topical yarrow is beneficial for patients with nipple fissures. Details: Preliminary clinical research in patients with inflamed nipples and/or nipple fissures shows that topical application with yarrow twice daily after breastfeeding for 7 days reduces redness and pain when compared with baseline. Yarrow 30 grams was boiled in 1 liter of water for 10 minutes. The benefits seen with yarrow were not significantly different from topical mountain honey or breast milk, both of which were also beneficial when compared with baseline (105359).
• Oral mucositis. It is unclear if gargling with yarrow is beneficial for oral mucositis. Details: Preliminary clinical research in patients with chemotherapy-induced oral mucositis shows that gargling with 15 mL of a routine solution containing yarrow distillate 50%, 4 times daily for 14 days, reduces symptom severity by 87%, compared with a worsening in severity in those using the routine solution alone. Of those using yarrow, all patients were able to eat solid foods at 14 days compared with about 40% of those using routine treatment alone. About 3.75 grams of yarrow flower was needed for each 7.5 mL of distillate and the solution was held for 3 minutes in the mouth before gargling (106664). It is unclear if the patients were adequately blinded, as the taste of the two solutions may have differed.
• Tonsillitis. Oral yarrow has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children 6-18 years of age with acute non-bacterial tonsillitis shows that taking a specific combination product (Imupret, Bionorica AG) containing yarrow and six other herbal ingredients along with standard care reduces the severity of tonsillitis symptoms when compared with standard care alone. Additionally, taking this combination product improved physician- and patient-rated assessments of general condition when compared with standard care alone (100347). It is not clear if these effects are due to yarrow, other ingredients, or the combination.
• Vaginal candidiasis. It is unclear if intravaginal yarrow is beneficial for vaginal candidiasis. Details: Clinical research in patients with vulvovaginal candidiasis shows that intravaginal application of 5 grams of a cream containing yarrow extract 2% for 7 days modestly reduces Candida growth and improves vulvar erythema and other general symptoms when compared with baseline. However, the cream was less effective overall than vaginal clotrimazole 1% cream (105360).
• Wound healing. It is unclear if topical yarrow is beneficial for wound healing. Details: Clinical research in postpartum adults who have had an episiotomy shows that applying approximately 1 cm of an ointment containing yarrow 5% over the clean and dried suture area twice daily for ten days reduces perineal pain, redness, and edema 1-2 weeks after the procedure when compared with placebo ointment or no treatment. However, using the yarrow ointment did not affect discharge time or reduce the occurrence of dehiscence (96910). More evidence is needed to rate yarrow for these uses.

(Read more about YARROW)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Oral Baikal skullcap 0.5-3.52 grams daily has been used with apparent safety for up to 8 weeks (92776,101738,101739,110023). However, a high quality assessment of safety has not been conducted. A specific product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been associated with an increased risk for liver and lung injury. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination. There is insufficient reliable information available about the safety of Baikal skullcap when used intravenously or topically.

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

(Read more about BAIKAL SKULLCAP)

POSSIBLY UNSAFE ...when used orally. The root, bark, and berries contain high amounts of tannins (6). Large doses may have mineralocorticoid activity (4). The root bark can also contain a carcinogen (5). There is insufficient reliable information available about the safety of bayberry for its other uses.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally or topically because of possible carcinogenic, or mineralocorticoid activities; avoid using (4,5).

(Read more about BAYBERRY)

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

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

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

(Read more about EYEBRIGHT)

LIKELY SAFE ...when used orally and appropriately, short-term. Feverfew has been used safely in studies lasting up to 4 months (6959,6960,6961,13239).

POSSIBLY UNSAFE ...when fresh feverfew leaves are chewed. Chewing raw or unprocessed feverfew leaves can cause oral inflammation, ulceration, swelling of the lips, and sometimes loss of taste (6959).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Feverfew might cause uterine contractions and abortion (12); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about FEVERFEW)

POSSIBLY SAFE ...when used orally and appropriately as a single dose (260,261). There is insufficient reliable information available about the safety of goldenseal when used as more than a single dose.

CHILDREN: LIKELY UNSAFE
when used orally in newborns. The berberine constituent of goldenseal can cause kernicterus in newborns, particularly preterm neonates with hyperbilirubinemia (2589).

PREGNANCY: LIKELY UNSAFE
when used orally. Berberine is thought to cross the placenta and may cause harm to the fetus. Kernicterus has developed in newborn infants exposed to goldenseal (2589).

LACTATION:
LIKELY UNSAFE when used orally. Berberine and other harmful constituents can be transferred to the infant through breast milk (2589). Use during lactation can cause kernicterus in the newborn and several resulting fatalities have been reported (2589).

(Read more about GOLDENSEAL)

POSSIBLY SAFE ...when used orally and appropriately. Stinging nettle root 360-600 mg has been used safely for up to 1 year (5093,11230,15195,76406,96744). ...when used topically and appropriately (12490).

PREGNANCY: LIKELY UNSAFE
when used orally due to possible abortifacient and uterine-stimulant effects (4,6,19).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about STINGING NETTLE)

LIKELY SAFE ...when used orally and appropriately, short-term. Turmeric products providing up to 8 grams of curcumin have been safely used for up to 2 months (10453,11144,11150,17953,79085,89720,89721,89724,89728,101347)(81036,101349,107110,107116,107117,107118,107121,109278,109283,114899) and products providing up to 1500 mg of curcumin daily have been safely used for up to 12 months (114898). Additionally, turmeric in doses up to 3 grams daily has been used with apparent safety for up to 3 months (102350,104146,104148,113357,114906). ...when used topically and appropriately (11148).

POSSIBLY SAFE ...when used as an enema, short-term. Turmeric extract in water has been used as a daily enema for up to 8 weeks (89729). ...when used topically as a mouthwash, short-term. A mouthwash containing 0.05% turmeric extract and 0.05% eugenol has been used safely twice daily for up to 21 days (89723).

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

PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts; turmeric might stimulate the uterus and increase menstrual flow (12).

LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food. There is insufficient reliable information available about the safety of using turmeric in medicinal amounts during lactation.

(Read more about TURMERIC)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Yarrow products that are thujone-free have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912); however, products containing thujone might not be safe. Thujone is a chemical that stimulates the central nervous system and is poisonous in large doses.

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (2,12,100346). Yarrow whole plant extract has been used with apparent safety at a dose of 250-500 mg daily for 12 months (100346). ...when used intravaginally as a cream containing yarrow extract 2% daily for 7 days (105360). There is insufficient reliable information available about the safety of yarrow when applied topically.

PREGNANCY: LIKELY UNSAFE
when used orally; yarrow is believed to be an abortifacient and affect the menstrual cycle (12).

LACTATION:
Insufficient reliable information available; avoid use.

(Read more about YARROW)

ALCOHOL (Ethanol) Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol.  Details In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might increase the risk of bleeding when used concomitantly with anticoagulant and antiplatelet drugs.  Details Preliminary clinical research suggests that taking capsules containing a combination of astragalus, goldthread, and Baikal skullcap daily for 4 weeks inhibits platelet aggregation; the effect seems to be similar to that of aspirin 50 mg daily (33075). It is unclear if this effect is due to Baikal skullcap, other ingredients, or the combination.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of Baikal skullcap with antidiabetes drugs might enhance blood glucose lowering effects.  Details Baicalein, a constituent of Baikal skullcap, has alpha-glucosidase inhibitory activity in vitro (6292). Animal research also suggests that Baikal skullcap enhances the antidiabetic effects of metformin (33408). However, in a small human study, taking Baikal skullcap extract did not enhance the antidiabetic effects of metformin, although it did modestly lower glucose levels during an oral glucose tolerance test (OGTT) (101738). Until more is known, use cautiously.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Baikal skullcap with antihypertensive drugs might have additive effects and increase the risk of hypotension.  Details Animal research suggests that baicalein, a constituent of Baikal skullcap, might lower blood pressure (33374).

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Baikal skullcap and antithyroid drugs may result in additive activity and increase the risk of hypothyroidism.  Details In an animal hyperthyroid model, Baikal skullcap improved levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) (101736). The clinical significance of this effect is unclear.

CNS DEPRESSANTS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties.  Details In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap may increase levels of drugs metabolized by CYP1A2 enzymes.  Details In vitro evidence suggests that constituents of Baikal skullcap inhibit the activity of CYP1A2 (33346,33484). This effect has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might increase levels of drugs metabolized by CYP2C19 enzymes.  Details In vitro evidence suggest that wogonin, a constituent of Baikal skullcap, modestly inhibits the activity of CYP2C19 enzymes (33484). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of large amounts of Baikal skullcap might interfere with hormone replacement therapy, due to competition for estrogen receptors.  Details In vitro evidence suggests that Baikal skullcap has estrogenic activity (16061).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might reduce lithium excretion and increase serum levels of lithium.  Details Baikal skullcap is thought to have diuretic properties, which may reduce lithium excretion (5541). The dose of lithium might need to be decreased.

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, Baikal skullcap might alter the levels and clinical effects of OATP substrates.  Details Some pharmacokinetic research shows that baicalin, a constituent of Baikal skullcap, can decrease plasma levels of rosuvastatin. The mechanism is thought to involve stimulation of the activity of the organic anion-transporting polypeptide 1B1 (OATP1B1), which transports rosuvastatin into the liver. This decreases plasma levels of the drug, but increases levels at the site of action in the liver. The degree to which rosuvastatin levels are affected depends on the OATP1B1 haplotype of the individual (16395). Baikal skullcap might also affect other OATP1B1 substrates (16396,16397,16398).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might increase levels of drugs transported by P-glycoprotein.  Details In vitro and animal research suggests that baicalein, oroxylin A, and wogonin, constituents of Baikal skullcap, can inhibit P-glycoprotein (33372,33395,33440,33462). This effect has not been reported in humans.

(Read more about BAIKAL SKULLCAP)

(Read more about BAYBERRY)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, eyebright might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal research suggests that eyebright lowers blood glucose levels (49393).

(Read more about EYEBRIGHT)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might have additive effects and increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.  Details Laboratory research suggests that feverfew may inhibit platelet aggregation (6935,6936,6942,6943,6944,6945,6951). Additionally, in one case report, a 36-year-old patient taking feverfew 2400 mg daily for 3 months experienced vaginal bleeding and a prolonged menstrual cycle, with a modest increase in partial thromboplastin time (PTT) and prothrombin time (PT) (107472).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP1A2.  Details Laboratory research shows that feverfew might inhibit CYP1A2 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP2C19.  Details Laboratory research shows that feverfew might inhibit CYP2C19 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP2C8.  Details Laboratory research shows that feverfew might inhibit CYP2C8 (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, feverfew might increase levels of drugs metabolized by CYP2C9.  Details Laboratory research shows that feverfew might inhibit CYP2C9 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP2D6.  Details Laboratory research shows that feverfew might inhibit CYP2D6 (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 = D Theoretically, feverfew might increase levels of drugs metabolized by CYP3A4.  Details Laboratory research shows that feverfew might inhibit CYP3A4 (12479,19361). So far, this interaction has not been reported in humans.

(Read more about FEVERFEW)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, goldenseal might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.  Details Goldenseal contains berberine. In vitro and animal research shows that berberine can inhibit platelet aggregation (33660,33694). However, this effect 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, goldenseal might increase the risk of hypoglycemia when used with antidiabetes drugs.  Details Goldenseal contains berberine. Clinical research shows that berberine can lower blood glucose levels (20579,34247,34265,34282). However, this effect has not been reported with goldenseal.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, goldenseal might increase the risk of hypotension when taken with antihypertensive drugs.  Details Goldenseal contains berberine. Animal research shows that berberine can have hypotensive effects (33692,34308). Also, an analysis of clinical research shows that taking berberine in combination with amlodipine can lower systolic and diastolic blood pressure when compared with amlodipine alone (91956). However, this effect has not been reported with goldenseal.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, goldenseal might increase the sedative effects of CNS depressants.  Details Goldenseal contains berberine. Animal research shows that berberine can have sedative effects (13519,33650,33664,33692). However, this effect 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, goldenseal might increase serum levels of drugs metabolized by CYP2C9.  Details In vitro research shows that goldenseal root extract can modestly inhibit CYP2C9. This effect may be due to its alkaloid constituents, hydrastine and berberine (21117). However, this effect has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Goldenseal might increase serum levels of drugs metabolized by CYP2D6.  Details Clinical and in vitro research shows that goldenseal can significantly inhibit CYP2D6 enzymes, potentially increasing levels of drugs metabolized by CYP2D6 (13536,16848,35907).

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, goldenseal might increase serum levels of drugs metabolized by CYP2E1.  Details In vitro research shows that goldenseal root extract can inhibit the activity of CYP2E1 (94140). However, this effect 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 Goldenseal might increase serum levels of drugs metabolized by CYP3A4.  Details Most clinical and in vitro research shows that goldenseal inhibits CYP3A4 enzyme activity and increases serum levels of CYP3A4 substrates, such as midazolam (6450,13536,21117,91740,111725). However, in one small clinical study, goldenseal did not affect the levels of indinavir, a CYP3A4 substrate, in healthy volunteers (10690,93578). This is likely due to the fact that indinavir has a high oral bioavailability, making it an inadequate probe for CYP3A4 interactions (13536,91740) and/or that it is primarily metabolized by hepatic CYP3A, while goldenseal has more potential to inhibit intestinal CYP3A enzyme activity (111725). Both goldenseal extract and its isolated constituents berberine and hydrastine inhibit CYP3A, with hydrastine possibly having more inhibitory potential than berberine (111725).

DEXTROMETHORPHAN (Robitussin DM, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, goldenseal might increase serum levels of dextromethorphan.  Details Goldenseal contains berberine. A small clinical study shows that berberine can inhibit cytochrome P450 2D6 (CYP2D6) activity and reduce the metabolism of dextromethorphan (34279).

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Goldenseal might increase serum levels of digoxin, although this effect is unlikely to be clinically significant.  Details Clinical research shows that goldenseal modestly increases digoxin peak levels by about 14% in healthy volunteers. However, goldenseal does not seem to affect other pharmacokinetic parameters such as area under the curve (AUC) (15132). This suggests that goldenseal does not cause a clinically significant interaction with digoxin. Digoxin is a P-glycoprotein substrate. Some evidence suggests that goldenseal constituents might affect P-glycoprotein; however, it is unclear whether these constituents inhibit or induce P-glycoprotein.

LOSARTAN (Cozaar) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, goldenseal might decrease the conversion of losartan to its active form.  Details Goldenseal contains berberine. A small clinical study shows that berberine inhibits cytochrome P450 2C9 (CYP2C9) activity and reduces the metabolism of losartan (34279). However, this effect has not been reported with goldenseal.

METFORMIN (Glucophage) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, goldenseal might reduce blood levels of metformin.  Details In vitro research shows that goldenseal extract decreases the bioavailability of metformin, likely by interfering with transport, intestinal permeability, or other processes involved in metformin absorption. It is unclear which, if any, of metformin's transporters are inhibited by goldenseal. Goldenseal does not appear to alter the clearance or half-life of metformin (105764).

OSELTAMIVIR (Tamiflu) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, goldenseal might reduce the therapeutic effects of oseltamivir by decreasing its conversion to its active form.  Details In vitro evidence suggests that goldenseal reduces the formation of the active compound from the prodrug oseltamivir (105765). The mechanism of action and clinical relevance is unclear.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, goldenseal might increase or decrease serum levels of P-glycoprotein (P-gp) substrates.  Details There is conflicting evidence about the effect of goldenseal on P-gp. In vitro research suggests that berberine, a constituent of goldenseal, modestly inhibits P-gp efflux. Other evidence suggests that berberine induces P-gp. In healthy volunteers, goldenseal modestly increases peak levels of the P-gp substrate digoxin by about 14%. However, it does not seem to affect other pharmacokinetic parameters such as area under the curve (AUC) (15132). This suggests that goldenseal is not a potent inhibitor of P-gp-mediated drug efflux. Until more is known, goldenseal should be used cautiously with P-gp substrates.

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, goldenseal might increase the sedative effects of pentobarbital.  Details Animal research shows that berberine, a constituent of goldenseal, can prolong pentobarbital-induced sleeping time (13519). However, this effect has not been reported with goldenseal.

TACROLIMUS (Prograf) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, goldenseal might increase serum levels of tacrolimus.  Details Goldenseal contains berberine. In a 16-year-old patient with idiopathic nephrotic syndrome who was being treated with tacrolimus 6.5 mg twice daily, intake of berberine 200 mg three times daily increased the blood concentration of tacrolimus from 8 to 22 ng/mL. Following a reduction of tacrolimus dosing to 3 mg daily, blood levels of tacrolimus decreased to 12 ng/mL (91954).

(Read more about GOLDENSEAL)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, stinging nettle might have additive effects with antidiabetes drugs.  Details Clinical research shows that stinging nettle might decrease blood glucose levels in patients with diabetes (91519,102865).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining stinging nettle with diuretic drugs may have additive effects.  Details Animal research suggests that the above ground parts and roots of stinging nettle may have a diuretic effect (1,4,11,76402).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, stinging nettle might reduce excretion and increase levels of lithium.  Details Animal research suggests that stinging nettle has diuretic and natriuretic properties, which could alter the excretion of lithium (76402). The dose of lithium might need to be decreased.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D There is some concern that stinging nettle might decrease the effects of anticoagulant drugs such as warfarin.  Details Stinging nettle contains a significant amount of vitamin K (19). When taken in large quantities, this might interfere with the activity of warfarin.

(Read more about STINGING NETTLE)

ALKYLATING AGENTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.  Details In vitro research suggests that curcumin, a constituent of turmeric, inhibits mechlorethamine-induced apoptosis of breast cancer cells by up to 70%. Also, animal research shows that curcumin inhibits cyclophosphamide-induced tumor regression (96126). However, some in vitro research shows that curcumin does not affect the apoptosis capacity of etoposide. Also, other laboratory research suggests that curcumin might augment the cytotoxic effects of alkylating agents. Reasons for the discrepancies may relate to the dose of curcumin and the specific chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have on alkylating agents.

AMLODIPINE (Norvasc) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Taking turmeric with amlodipine may increase levels of amlodipine.  Details Animal research shows that giving amlodipine 1 mg/kg as a single dose following the use of turmeric extract 200 mg/kg daily for 2 weeks increases the maximum concentration and area under the curve by 53% and 56%, respectively, when compared with amlodipine alone (107113). Additional animal research shows that taking amlodipine 1 mg/kg with a curcumin 2 mg/kg pretreatment for 10 days increases the maximum concentration and area under the curve by about 2-fold when compared with amlodipine alone (103099).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Turmeric may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.  Details Curcumin, a constituent of turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271). Furthermore, two case reports have found that taking turmeric along with warfarin or fluindione was associated with an increased international normalized ratio (INR) (89718,100906). However, one clinical study in healthy volunteers shows that taking curcumin 500 mg daily for 3 weeks, alone or with aspirin 100 mg, does not increase antiplatelet effects or bleeding risk (96137). It is possible that the dose of turmeric used in this study was too low to produce a notable effect.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking turmeric with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research and case reports suggest that curcumin, a turmeric constituent, can reduce blood glucose levels in patients with diabetes (79692,79984,80155,80313,80315,80476,80553,81048,81219). Furthermore, clinical research in adults with type 2 diabetes shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg decreased postprandial glucose levels for up to 24 hours when compared with glyburide alone, despite the lack of a significant pharmacokinetic interaction (96133). Other clinical studies in patients with diabetes show that taking curcumin daily can reduce blood glucose levels when compared with placebo (104149,114898,114900).

ANTITUMOR ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.  Details In vitro and animal research shows that curcumin, a constituent of turmeric, inhibits doxorubicin-induced apoptosis of breast cancer cells by up to 65% (96126). However, curcumin does not seem to affect the apoptosis capacity of daunorubicin. In fact, some research shows that curcumin might augment the cytotoxic effects of antitumor antibiotics, increasing their effectiveness. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effects, if any, antioxidants such as turmeric have on antitumor antibiotics.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase or decrease levels of drugs metabolized by CYP1A1. However, research is conflicting.  Details Most in vitro and animal research suggests that the turmeric constituent, curcumin, INHIBITS CYP1A1, primarily in the liver (15823,21495,80876,81411). However, some evidence from in vitro research suggests that curcumin may INDUCE CYP1A1 in the intestines (21500).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.  Details In vitro and animal research show that the turmeric constituent, curcumin, inhibits CYP1A2 (15823,21497,81304). However, other in vitro research suggests that curcumin does not significantly affect CYP1A2 (22000).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric might increase levels of drugs metabolized by CYP3A4.  Details In vitro and animal research show that turmeric and its constituents curcumin and curcuminoids inhibit CYP3A4 (21497,21498,21499). Also, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking turmeric and cancer medications that are CYP3A4 substrates, including everolimus, ruxolitinib, ibrutinib, and palbociclib, and bortezomib (111644). In another case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels after consuming turmeric powder at a dose of 15 or more spoonfuls daily for ten days prior. It was thought that turmeric increased levels of tacrolimus due to CYP3A4 inhibition (93544). Conversely, other in vitro research suggests that turmeric induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans.

DOCETAXEL (Taxotere) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase blood levels of oral docetaxel.  Details Animal research suggests that the turmeric constituent, curcumin, enhances the oral bioavailability of docetaxel (80999). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

ESTROGENS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, large amounts of turmeric might interfere with hormone replacement therapy through competition for estrogen receptors.  Details In vitro research shows that curcumin, a constituent of turmeric, displaces the binding of estrogen to its receptors (21486).

GLYBURIDE (Diabeta, others) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking turmeric and glyburide in combination might increase the risk of hypoglycemia.  Details Clinical research shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 diabetes. While maximal blood concentrations of glyburide were not affected, turmeric modestly decreased postprandial glucose levels for up to 24 hours when compared to glyburide alone, possibly due to the hypoglycemic effect of turmeric demonstrated in animal research (96133).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs.  Details There is concern that turmeric might cause hepatotoxicity, especially when highly bioavailable formulations are used in high doses (103633,107122,109288,110221).

LOSARTAN (Cozaar) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase the effects of losartan.  Details Research in hypertensive rats shows that taking turmeric can increase the hypotensive effects of losartan (110897).

METHOTREXATE (Trexall, others) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might have additive effects when used with hepatotoxic drugs such as methotrexate.  Details In one case report, a 39-year-old female taking methotrexate, turmeric, and linseed oil developed hepatotoxicity (111644).

NORFLOXACIN (Noroxin) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase the effects and adverse effects of norfloxacin.  Details Animal research shows that taking curcumin, a turmeric constituent, can increase blood levels of orally administered norfloxacin (80863).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase blood levels of OATP4C1 substrates.  Details In vitro research shows that the turmeric constituent curcumin competitively inhibits OATP4C1 transport. This transporter is expressed in the kidney and facilitates the renal excretion of certain drugs (113337). Theoretically, taking turmeric might decrease renal excretion of OATP substrates.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.  Details In vitro and animal research shows that curcuminoids and other constituents found in turmeric can inhibit P-glycoprotein expression and activity (21472,21473,21474,21475,21476,21477,21478,21479,21480)(21482,21484,111644).

PACLITAXEL (Abraxane, Onxol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.  Details Clinical research in adults with breast cancer receiving intravenous paclitaxel suggests that taking turmeric may modestly alter paclitaxel pharmacokinetics. Patients received paclitaxel on day 1, followed by either no treatment or turmeric 2 grams daily from days 2-22. Pharmacokinetic modeling suggests that turmeric reduces the maximum concentration and area under the curve of paclitaxel by 12.1% and 7.7%, respectively. However, these changes are not likely to be considered clinically relevant (108876). Conversely, animal research suggests that curcumin, a constituent of turmeric, enhances the oral bioavailability of paclitaxel (22005). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

SULFASALAZINE (Azulfidine) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Turmeric might increase the effects and adverse effects of sulfasalazine.  Details Clinical research shows that taking the turmeric constituent, curcumin, can increase blood levels of sulfasalazine by 3.2-fold (81131).

TACROLIMUS (Prograf) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric might increase the effects and adverse effects of tacrolimus.  Details In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting at the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to cytochrome P450 3A4 (CYP3A4) inhibition (93544). In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4 (21497,21498,21499).

TALINOLOL Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Turmeric may reduce the absorption of talinolol in some situations.  Details Clinical research shows that taking curcumin for 6 days decreases the bioavailability of talinolol when taken together on the seventh day (80079). The clinical significance of this effect is unclear.

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, turmeric might reduce the levels and clinical effects of tamoxifen.  Details In a small clinical trial in patients with breast cancer taking tamoxifen 20-30 mg daily, adding curcumin 1200 mg plus piperine 10 mg three times daily reduces the 24-hour area under the curve of tamoxifen and the active metabolite endoxifen by 12.8% and 12.4%, respectively, as well as the maximum concentrations of tamoxifen, when compared with tamoxifen alone. However, in the absence of piperine, the area under the curve for endoxifen and the maximum concentration of tamoxifen were not significantly reduced. Effects were most pronounced in patients who were extensive cytochrome P450 (CYP) 2D6 metabolizers (107123).

TOPOISOMERASE I INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric has antioxidant effects. There is some concern that this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.  Details In vitro research shows that curcumin, a constituent of turmeric, inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71% (96126). However, other in vitro research shows that curcumin augments the cytotoxic effects of camptothecin. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agents. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Turmeric might increase the risk of bleeding with warfarin.  Details One case of increased international normalized ratio (INR) has been reported for a patient taking warfarin who began taking turmeric. Prior to taking turmeric, the patient had stable INR measurements. Within a few weeks of starting turmeric supplementation, the patient's INR increased to 10 (100906). Additionally, curcumin, the active constituent in turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271), which may produce additive effects when taken with warfarin.

(Read more about TURMERIC)

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking yarrow with lithium might increase the levels and adverse effects of lithium.  Details Animal research shows that yarrow has diuretic activity (106018). Theoretically, due to these potential diuretic effects, yarrow might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

(Read more about YARROW)

General ...Orally, Baikal skullcap seems to be well-tolerated. There is currently a limited amount of information on the adverse effects of intravenous and topical Baikal skullcap.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, erythema, nausea, pruritus, and vomiting.
Intravenously: Skin reactions.
Topically: Dermatitis.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity and hypersensitivity pneumonitis have been reported with a specific combination product (Limbrel, Primus Pharmaceuticals) containing extracts of Baikal skullcap and catechu.

Cardiovascular ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, elevated triglyceride levels occurred in 1 of 10 patients who received 400 mg every 8 hours and 2 of 10 patients treated with 600 mg every 8 hours, compared with 0 of 10 patients who received 200 mg every 8 hours and 0 of 6 patients who received placebo. Triglyceride elevations were considered mild and resolved after discontinuation (110023).

Dermatologic ...Orally, taking Baikal skullcap may cause erythema and pruritus (105867). Intravenously, Baikal skullcap as part of a Tanreqing injection has been associated with reports of skin reactions in some pediatric patients (96281).
Topically, several cases of allergic contact dermatitis have been reported after applying sunscreen containing Baikal skullcap extract (105869,105870). Allergic contact dermatitis has also been reported after applying a facial cream (Resveratrol BE, Skinceuticals) containing Baikal skullcap root extract 0.5% and resveratrol 1%. Patch testing identified a positive reaction to both ingredients (110024). Baikal skullcap-induced dermatitis appears to respond to treatment with a topical corticosteroid and calcineurin inhibitor (105870).

Gastrointestinal ...Orally, use of Baikal skullcap has been associated with epigastric pain, abdominal pain, constipation, diarrhea, nausea, and vomiting (101738,105867).

Hepatic ...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of acute liver damage. There have been at least five published reports of liver damage associated with this product. In all cases, the patients were females aged 54-68 years taking doses of 250-500 mg twice daily for 1-3 months. Signs and symptoms included jaundice, pruritus, abdominal pain, fever, rash, and elevated serum bilirubin and liver transaminase levels. All patients fully recovered and levels normalized within 3 months after discontinuation (18009,96282). In addition to these published case reports, approximately 30 liver-related adverse events have been reported to the manufacturer of this product (18009). The mechanism of hepatotoxicity is unclear (18009,18010); it is estimated that the incidence of hepatotoxicity with this product is around 1 in 10,000, although the actual incidence is unknown (18010). In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.
Hepatotoxicity has also been reported in two patients taking a specific dietary supplement (Move Free Advanced, Reckitt Benckiser) containing Baikal skullcap, black catechu, glucosamine, chondroitin, and hyaluronic acid (33460) and in a patient taking Baikal skullcap, elderflower, horseradish, and white willow (101737). The investigators determined that the hepatotoxicity was likely caused by Baikal skullcap in these cases (33460,101737). Additionally, cases of liver injury are reported in 4 of 37 patients taking various Kampo formulations containing Baikal skullcap and other herbs daily. Patients presented with elevated liver function tests 7 to 38 days after consumption (112179). It is unclear if this adverse effect is from Baikal skullcap, other ingredients, or the combination.
In a small study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, liver transaminase elevations occurred in 2 of 10 patients who received 400 mg every 8 hours for 6 days, compared with 0 of 6 patients who received placebo. No patients receiving either 200 mg or 600 mg every 8 hours experienced liver transaminase elevations. The elevations were considered mild and resolved after discontinuation (110023).

Pulmonary/Respiratory ...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of hypersensitivity pneumonitis. Symptoms include fever, chills, headache, cough, chronic bronchitis, shortness of breath, weight loss, and fatigue. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.

Renal ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, proteinuria of undefined severity occurred in 1 of 10 patients who received 200 mg every 8 hours for 6 days, 3 of 10 patients who received 400 mg every 8 hours for 6 days, and 5 of 10 patients who received 600 mg every 8 hours for 6 days, compared with 1 of 6 patients who received placebo. The proteinuria was considered mild and resolved after discontinuation (110023).

(Read more about BAIKAL SKULLCAP)

General ...Orally, bayberry can cause gastrointestinal irritation, vomiting, and liver damage, possibly due to its tannin content. It can also act as an irritant and sensitizer (6).

Dermatologic ...Orally, bayberry can act as an irritant and sensitizer (6).

Gastrointestinal ...Orally, bayberry can cause gastrointestinal irritation and vomiting, possibly due to its tannin content (6).

Hepatic ...Orally, bayberry can cause liver damage, possibly due to its tannin content (6).

Immunologic ...Airborne bayberry pollen is a common cause of allergic respiratory symptoms (33888,33916).

Pulmonary/Respiratory ...Airborne bayberry pollen is a common cause of allergic respiratory symptoms (33888,33916).

(Read more about BAYBERRY)

General ...Orally, eyebright is generally well tolerated when used in food amounts. Topically, eyebright might be unsafe due to the potential for contamination.

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

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

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

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

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

(Read more about EYEBRIGHT)

General ...Orally, feverfew is generally well tolerated. Chewing fresh feverfew leaves is more likely to cause mouth ulceration and other adverse effects of the mouth, lips, and tongue when compared with commercial feverfew preparations.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, constipation, diarrhea, flatulence, heartburn, and nausea. Skin rash may occur in sensitive individuals.
Topically: Dermatitis in sensitive individuals.

Cardiovascular ...Orally, feverfew has been associated with palpitations in one patient in a clinical study (6959).

Dermatologic ...Orally, feverfew can cause skin rash (12383). Topically, allergic contact dermatitis can occur (6958,42856,42891). Allergic reactions to feverfew may be more likely in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Gastrointestinal ...Orally, feverfew can cause gastrointestinal symptoms such as heartburn, nausea, diarrhea, constipation, abdominal pain and bloating, and flatulence (6938,6959,12383,22602). Oral numbness has also been reported when feverfew has been taken sublingually in combination with ginger (22602). The traditional method of feverfew administration-chewing fresh feverfew leaves-can result in mouth ulceration, inflamed oral mucosa and tongue, swelling of the lips, and occasionally, loss of taste (6935,6959). Mouth ulceration might result from direct contact with feverfew leaves during chewing, possibly attributable to the sesquiterpene lactone constituent (6959). Some researchers suggest that mouth ulceration is a systemic effect, but one study using dried feverfew capsules reported a higher incidence of mouth ulcers in subjects taking placebo than feverfew (6935,6959,6960).

Genitourinary ...Orally, feverfew has been associated with menstrual changes in one patient in a clinical study (6959) and in one case report involving a 36-year-old patient taking 800 mg of feverfew three times daily for 3 months (107472).

Immunologic ...Orally and topically, feverfew may cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Musculoskeletal ...Orally, feverfew has been associated with joint stiffness in two patients in a clinical study (6959). Discontinuation of oral feverfew after long-term use may cause "post-feverfew syndrome", which includes symptoms such as muscle and joint stiffness (6959,12153).

Neurologic/CNS ...Discontinuation of oral feverfew after long-term use may cause "post-feverfew syndrome", which includes symptoms such as anxiety, headaches, and insomnia (6959,12153).

Other ...Orally, feverfew may cause weight gain (12383).

(Read more about FEVERFEW)

General ...There is limited reliable information available about the safety of goldenseal when used in more than a single dose. Berberine, a constituent of goldenseal, is generally well tolerated when used orally.
Most Common Adverse Effects:
Orally: Berberine, a constituent of goldenseal, can cause abdominal distension, abdominal pain, bitter taste, constipation, diarrhea, flatulence, headache, nausea, and vomiting.

Dermatologic ...Orally, berberine, a constituent of goldenseal, may cause rash. However, this appears to be rare (34285). A case of photosensitivity characterized by pruritic, erythematous rash on sun-exposed skin has been reported in a 32-year-old female taking a combination product containing goldenseal, ginseng, bee pollen, and other ingredients. The rash resolved following discontinuation of the supplement and treatment with corticosteroids (33954). It is not clear if this adverse effect is due to goldenseal, other ingredients, or the combination.

Endocrine ...A case of severe, reversible hypernatremia has been reported in an 11-year-old female with new-onset type 1 diabetes and diabetic ketoacidosis who took a goldenseal supplement (52592).

Gastrointestinal ...Orally, berberine, a constituent of goldenseal, may cause diarrhea, constipation, flatulence, vomiting, abdominal pain, abdominal distention, and bitter taste (33648,33689,34245,34247,34285,91953). Theoretically, these effects may occur in patients taking goldenseal. However, this hasn't been reported in clinical research or case reports.

Neurologic/CNS ...Orally, berberine, a constituent of goldenseal, may cause headache when taken in a dose of 5 mg/kg daily (33648). Theoretically, this may occur with goldenseal, but this hasn't been reported in clinical research or case reports.

(Read more about GOLDENSEAL)

General ...Orally, stinging nettle seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea.
Topically: Contact with the raw plant causes itching, rash, and stinging.

Dermatologic ...Topically, fresh stinging nettle leaves and stalk can cause localized rash, itching, and stinging (12490,76399,76412,76414,76417,76428,76448,96746). Usually, short exposure to stinging nettle results in a transient urticarial reaction and a stinging sensation which may persist for more than 12 hours (76399,76414,76417,96746). In one report, a patient placed a fresh stinging nettle leaf on the tongue to suck out the sap of the leaf. Severe tongue edema, pain, and urticaria developed within 5 minutes. Symptoms continued for several hours after the leaf was removed (15197). In another case report, a young couple intoxicated with methamphetamine fell and laid in a stinging nettle bush for 20 minutes, after which urticaria and pain continued for 2-3 weeks, and a heightened sensitivity to cold persisted for several months (96746).

Endocrine ...A case of gynecomastia has been reported for a 33-year-old male who consumed stinging nettle tea 2 cups daily for one month prior to symptom onset. The condition subsided one month after discontinuing stinging nettle tea (76410).
There have been two cases of galactorrhea associated with the consumption of stinging nettle for one month (76410,108902). In one case, a 33-year-old female consuming stinging nettle tea showed high levels of estradiol and low levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). The levels of these hormones normalized 6 weeks after discontinuing stinging nettle tea (76410). In the other case report describing a 30-year-old female self-treating with stinging nettle 500 mg daily, hormone levels were not reported; however, a mammogram showed scattered areas of fibroglandular density and benign-appearing calcifications. This patient had complete resolution of symptoms 1 week after discontinuation of stinging nettle (108902).

Gastrointestinal ...Orally, stinging nettle root can cause gastrointestinal complaints, including diarrhea and constipation (1,7,11230). Stinging nettle above ground parts may cause mild gastrointestinal discomfort when taken on an empty stomach (7035). Stinging nettle juice may cause diarrhea (1). One patient taking a combination product containing stinging nettle root extract and pygeum bark extract (Prostatonin, Pharmaton) experienced continual gastrointestinal pain and hyperperistalsis. It is not clear if this effect was due to stinging nettle or pygeum (70230).

Genitourinary ...There is a case report of decreased ejaculatory volume associated with an herbal blend product containing stinging nettle root extract, saw palmetto extract, pumpkin seed oil extract, lemon bioflavonoid extract, and beta-carotene (5093). It is unclear if this was due to stinging nettle, other ingredients, or the combination.

Hepatic ...A case of idiosyncratic drug-induced liver disease (DILI) is reported in a 36-year-old female who presented with abdominal pain after 1 month of taking an herbal liver detox tea containing stinging nettle and other ingredients. Remarkable laboratory values included elevated liver enzymes, alkaline phosphatase, and total bilirubin. The patient received a loading dose of N-acetylcysteine and was hospitalized for 12 days (112178). However, it is unclear if the adverse effect was due to the stinging nettle, other ingredients, or the combination.

Other ...Orally, stinging nettle root can cause sweating (1,7).

(Read more about STINGING NETTLE)

General ...Orally and topically, turmeric is generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, dyspepsia, diarrhea, distension, gastroesophageal reflux, nausea, and vomiting.
Topically: Curcumin, a constituent of turmeric, can cause contact urticaria and pruritus.

Cardiovascular ...Orally, a higher dose of turmeric in combination with other ingredients has been linked to atrioventricular heart block in one case report. It is unclear if turmeric caused this adverse event or if other ingredients or a contaminant were the cause. The patient had taken a combination supplement containing turmeric 1500-2250 mg, black soybean 600-900 mg, mulberry leaves, garlic, and arrowroot each about 300-450 mg, twice daily for one month before experiencing atrioventricular heart block. Heart rhythm normalized three days after discontinuation of the product. Re-administration of the product resulted in the same adverse effect (17720).

Dermatologic ...Following occupational and/or topical exposure, turmeric or its constituents curcumin, tetrahydrocurcumin, or turmeric oil, can cause allergic contact dermatitis (11146,79270,79470,79934,81410,81195). Topically, curcumin can also cause rash or contact urticaria (79985,97432,112117). In one case, a 60-year-old female, with no prior reactivity to regular oral consumption of turmeric products, developed urticaria after topical application of turmeric massage oil (97432). A case of pruritus has been reported following topical application of curcumin ointment to the scalp for the treatment of melanoma (11148). Yellow discoloration of the skin has been reported rarely in clinical research (113356). Orally, curcumin may cause pruritus, but this appears to be relatively uncommon (81163,97427,104148,114899). Pitting edema may also occur following oral intake of turmeric extract, but the frequency of this adverse event is less common with turmeric than with ibuprofen (89720). A combination of curcumin plus fluoxetine may cause photosensitivity (89728).

Gastrointestinal ...Orally, turmeric can cause gastrointestinal adverse effects (107110,107112,112118), including constipation (81149,81163,96135,113355), flatulence and yellow, hard stools (81106,96135), nausea and vomiting (10453,17952,89720,89728,96127,96131,96135,97430,112117,112118), diarrhea or loose stool (10453,17952,18204,89720,96135,110223,112117,112118,114898,114899), dyspepsia (17952,89720,89721,96161,112118), gastritis (89728), distension and gastroesophageal reflux disease (18204,89720), abdominal fullness and pain (81036,89720,96161,97430,114898,114899), epigastric burning (81444), and tongue staining (89723).

Hepatic ...Orally, turmeric has been associated with liver damage, including non-infectious hepatitis, cholestasis, and hepatocellular liver injury. There have been at least 70 reports of liver damage associated with taking turmeric supplements for at least 2 weeks and for up to 14 months. Most cases of liver damage resolved upon discontinuation of the turmeric supplement. Sometimes, turmeric was used concomitantly with other supplements and medications (99304,102346,103094,103631,103633,103634,107122,109288,110221). The Drug-Induced Liver Injury Network (DILIN) has identified 10 cases of liver injury which were considered to be either definitely, highly likely, or probably associated with turmeric; none of these cases were associated with the use of turmeric in combination with other potentially hepatotoxic supplements. Most patients (90%) presented with hepatocellular pattern of liver injury. The median age of these case reports was 56 years and 90% identified as White. In these case reports, the carrier frequency on HLAB*35:01 was 70%, which is higher than the carrier frequency found in the general population. Of the ten patients, 5 were hospitalized and 1 died from liver injury (109288).
It is not clear if concomitant use with other supplements or medications contributes to the risk for liver damage. Many case reports did not report turmeric formulation, dosing, or duration of use (99304,103094,103631,103634,109288). However, at least 10 cases involved high doses of curcumin (250-1812.5 mg daily) and the use of highly bioavailable formulations such as phytosomal curcumin and formulations containing piperine (102346,103633,107122,109288,110221).

Neurologic/CNS ...Orally, turmeric has been associated with headache and vertigo (81163,114898).

Psychiatric ...Orally, the turmeric constituent curcumin or a combination of curcumin and fluoxetine can cause giddiness, although this event seems to be uncommon (81206,89728).

Renal ...Orally, turmeric has been linked to one report of kidney failure, although the role of turmeric in this case is unclear. A 69-year-old male developed kidney failure related to calcium oxalate deposits in the renal tubules following supplementation with turmeric 2 grams daily for 2 years as an anti-inflammatory for pelvic pain. While turmeric is a source of dietary oxalates, pre-existing health conditions and/or chronic use of antibiotics may have contributed to the course of disease (113343).

Other ...There is a single case report of death associated with intravenous use of turmeric. However, analysis of the treatment vial suggests that the vial contained only 0.023% of the amount of curcumin listed on the label. Also, the vial had been diluted in a solution of ungraded polyethylene glycol (PEG) 40 castor oil that was contaminated with 1.25% diethylene glycol. Therefore the cause of death is unknown but is unlikely to be related to the turmeric (96136).

(Read more about TURMERIC)

General ...Orally and intravaginally, yarrow seems to be well tolerated.
Most Common Adverse Effects:
Topically: Dermatitis.

Dermatologic ...Topically, yarrow can cause atopic or allergic dermatitis or urticaria due to its sesquiterpene lactone content (52558,68385,77007). Yarrow has also been reported to cause phototoxic and photo-allergic dermatitis and airborne contact dermatitis (68385).
Intravaginally, aggravated facial acne was reported by 1 of 40 patients in a clinical trial (105360).

Endocrine ...Intravaginally, an early menses was reported by 1 of 40 patients in a clinical trial (105360).

Genitourinary ...Intravaginally, aggravated vaginal pruritus and dryness were reported by 1 of 40 patients in a clinical trial (105360).

Immunologic ...Topically, yarrow can cause atopic or allergic dermatitis or urticaria due to its sesquiterpene lactone content (52558,68385,77007,96911). It has also been reported to cause phototoxic and photo-allergic dermatitis and airborne contact dermatitis (68385). In one 44-year-old female, handling yarrow flowers resulted in rhinitis and asthma (96911).

(Read more about YARROW)