Healthy Pitta by Banyan Botanicals

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there is interest in using oral Asparagus racemosus for anxiety, there is insufficient reliable information about the clinical effects of Asparagus racemosus for this condition.
• Athletic performance. It is unclear if oral Asparagus racemosus is beneficial for improving athletic performance. Details: In recreationally trained males, taking Asparagus racemosus 500 mg daily for 8 weeks during bench press training increases the number of repetitions before exhaustion, and allows a greater increase in training loads, when compared with placebo (106413).
• Bronchitis. Although there is interest in using oral Asparagus racemosus for bronchitis, there is insufficient reliable information about the clinical effects of Asparagus racemosus for this condition.
• Cancer. Although there is interest in using oral Asparagus racemosus for cancer, there is insufficient reliable information about the clinical effects of Asparagus racemosus for this purpose.
• Dementia. Although there is interest in using oral Asparagus racemosus for dementia, there is insufficient reliable information about the clinical effects of Asparagus racemosus for this condition.
• Diabetes. Although there is interest in using oral Asparagus racemosus for diabetes, there is insufficient reliable information about the clinical effects of Asparagus racemosus for this condition.
• HIV/AIDS. Although there is interest in using oral Asparagus racemosus for HIV/AIDS, there is insufficient reliable information about the clinical effects of Asparagus racemosus for this condition.
• Lactation. Oral Asparagus racemosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In mothers who have to supplement their breast milk or who have infants with below normal weight gain, taking an herbal mixture containing Asparagus racemosus as 2 teaspoons twice daily for 4 weeks does not increase breast milk production, infant weight gain velocity, or prolactin levels (32588). Per 100 grams, the herbal mixture contained Asparagus racemosus 15 grams, dill 1 gram, morning glory 1 gram, licorice 2.5 grams, cumin 0.5 grams, and panchatrinamol 1 gram. Another small clinical study in postpartum mothers in India shows that consuming Asparagus racemosus in the form of 1 daily granola bar that contains Asparagus racemosus and other ingredients (Shavari Bar, Act Life Sciences Ltd.) for 4 days starting the day after delivery increases breast milk volume by about 15 mL and shortens the time to breast fullness when compared with placebo (111721). However, it is unclear whether any improvement is clinically significant, especially in the longer term. Additionally, the dose of Asparagus racemosus was not specified which limits the interpretation of these results.
• Muscle strength. It is unclear if oral Asparagus racemosus is beneficial for improving muscle strength. Details: A very small clinical study in physically active postmenopausal patients shows that taking Asparagus racemosus 1000 mg daily for 6 weeks improves hand grip strength, but not knee extensor strength, when compared with placebo (110736).
• Sexual desire. Although there is interest in using oral Asparagus racemosus for sexual desire, there is insufficient reliable information about the clinical effects of Asparagus racemosus for this purpose.
• Tuberculosis. Although there is interest in using oral Asparagus racemosus for tuberculosis, there is insufficient reliable information about the clinical effects of Asparagus racemosus for this condition. More evidence is needed to rate Asparagus racemosus for these uses.

(Read more about ASPARAGUS RACEMOSUS)

POSSIBLY EFFECTIVE

• Kidney stones (nephrolithiasis). Although some research disagrees, most clinical research shows that taking chanca piedra might improve clearance and decrease the size of kidney stones. However, it seems that disease severity, stone location, and chanca piedra dose and/or formulation may alter the likelihood of benefit. Details: Preliminary clinical research in adults with kidney stones shows that taking a specific chanca piedra product (Uriston) 2 grams orally daily for up to 3 months after undergoing 1-3 extracorporeal shock wave lithotripsy sessions increases clearance of kidney stones within 30-60 days by 1-2 times that of control (41224). Other preliminary clinical research in patients with kidney stones smaller than 10 mm also shows that drinking a chanca piedra tea, prepared with 4.5 grams of dried extract in 250 mL boiled water, twice daily for 12 weeks decreases the number of kidney stones by 38% and kidney stone size by 40% when compared with baseline (99849). However, a small clinical trial in adults with kidney stones failed to demonstrate beneficial effects from chanca piedra extract 450 mg three times daily orally for 3 months (41202). Some subgroup and other analyses also suggest that chanca piedra may be more effective in patients with hyperoxaluria or hyperuricosuria at baseline or those with smaller kidney stones of less than 6 mm or 10 mm (41224,99849,102692). Preliminary clinical research also shows that, in patients taking chanca piedra leaf extract 225 mg with magnesium stearate 152 mg and vitamin B6 2 mg twice daily for 3 months, stone-free status occurs in about 55% of patients with middle or upper kidney stones and about 14% of those with lower stones when compared with baseline (102692).

LIKELY INEFFECTIVE

• Hepatitis B. Most clinical research shows that oral chanca piedra is not effective for treating hepatitis B. Details: Despite preliminary clinical research suggesting that chanca piedra may be beneficial in patients with hepatitis B (41287), multiple follow-up clinical trials show that taking chanca piedra 200-900 mg three times daily for 1-6 weeks is not effective for treating hepatitis B, decreasing the duration of acute hepatitis B, or decreasing levels of hepatitis B surface antigen (HBsAg) (3924,3925,41180,41242,41255,41259,41294,41318).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abdominal pain. Although there has been interest in using oral chanca piedra for abdominal pain, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Anemia of chronic disease. Although there has been interest in using oral chanca piedra for anemia of chronic disease, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Asthma. Although there has been interest in using oral chanca piedra for asthma, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Benign prostatic hyperplasia (BPH). Oral chanca piedra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with BPH, some of whom were already receiving treatment for their symptoms, shows that taking a specific product containing water-soluble extracts of chanca piedra, boldo, goldenrod, fireweed, and spiny restharrow (Fluxonorm, Omega Pharma) for 30 days improves lower urinary tract symptom scores by about 50% when compared with baseline. Maximum urinary flow rate and quality of life were also improved when compared with baseline (106432). The validity of these findings is limited by the lack of a comparator group.
• Colic. Although there has been interest in using oral chanca piedra for colic, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Diabetes. It is unclear if oral chanca piedra is beneficial in patients with diabetes. Details: Preliminary clinical research in patients with types 2 diabetes shows that taking chanca piedra extract 12.5 grams orally twice daily for 7 days does not affect fasting or postprandial blood glucose levels when compared with baseline. The extract was prepared as 25 grams boiled in 200 mL of water (41186). The validity of this study is limited by the lack of a comparator group.
• Gallbladder disease. Although there has been interest in using oral chanca piedra for gallbladder disease, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Gastric cancer. Although there has been interest in using oral chanca piedra for gastric cancer, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Gonorrhea. Although there has been interest in using oral chanca piedra for gonorrhea, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Hangover. It is unclear if oral chanca piedra is beneficial in patients with hangover. Details: Preliminary clinical research in a small number of healthy adults shows that taking a standardized extract of chanca piedra (PHYLLPRO, Biotropics Malaysia Berhad) 375 mg orally twice daily for 10 days prior to heavy alcohol consumption may improve alcohol clearance, but does not improve hangover symptom scores or mood scores, when compared with placebo (99846). However, the study may have been inadequately powered to detect a difference between groups.
• Hypertension. It is unclear if oral chanca piedra is beneficial in patients with hypertension. Details: Preliminary clinical research in patients with hypertension shows that taking chanca piedra 1.6 grams orally three times daily for 10 days does not reduce systolic or diastolic blood pressure when compared with baseline (3928). The validity of this study is limited by the lack of a comparator group.
• Intestinal parasite infection. Although there has been interest in using oral chanca piedra for intestinal parasite infection, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Lymphedema. Although there has been interest in using oral chanca piedra for lymphedema, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Malaria. Although there has been interest in using oral chanca piedra for malaria, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Miscarriage. Although there has been interest in using oral chanca piedra for miscarriage, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Osteoarthritis. It is unclear if topical chanca piedra is beneficial in patients with osteoarthritis. Details: Preliminary clinical research in patients with knee osteoarthritis shows that topical application of a chanca piedra gel with phonophoresis once daily for 10 days reduces pain and improves function when compared with placebo gel. Pain was reduced by 78%, compared with a reduction of 44% in those using the placebo gel, and patients using chanca piedra were able to walk 62 meters farther in 6 minutes when compared with placebo gel (102691).
• Premature ejaculation. Oral chanca piedra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with premature ejaculation shows that taking a specific combination product containing chanca piedra, cardamom, vitamin B6, tribulus, tryptophan, thiamine, and winter savory (Eiacumev, Farmaceutica MEV) orally once daily for 3 months improves premature ejaculation severity scores and increases time to ejaculation when compared with sexual counseling. Time to ejaculation increased by around 30 seconds when compared with control (97016). The validity of this study is limited by the lack of randomization and placebo-control.
• Pruritus. Although there has been interest in using oral chanca piedra for pruritus, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Respiratory tract infections. Although there has been interest in using oral chanca piedra for respiratory tract infections, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Sexual dysfunction. Although there has been interest in using oral chanca piedra for sexual dysfunction, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Solid tumors. Although there has been interest in using oral chanca piedra for solid tumors, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Tonsillopharyngitis. Oral chanca piedra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with tonsillopharyngitis shows that taking chanca piedra 50 mg and black seed 360 mg orally three times daily for 7 days moderately relieves pain when compared with placebo (36199).
• Urinary tract infections (UTIs). Although there has been interest in using oral chanca piedra for UTIs, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Vaginitis. Although there has been interest in using oral chanca piedra for vaginitis, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose.
• Vertigo. Although there has been interest in using oral chanca piedra for vertigo, there is insufficient reliable information about the clinical effects of chanca piedra for this purpose. More evidence is needed to rate chanca piedra for these uses.

(Read more about CHANCA PIEDRA)

POSSIBLY EFFECTIVE

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

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about FENNEL)

POSSIBLY EFFECTIVE

• Burns. Topical gotu kola seems to improve the rate of burn healing. Details: Clinical research shows that applying a cream containing gotu kola 3% once daily to second degree burns increases the rate of re-epithelialization and complete healing by about 7 days when compared with silver sulfadiazine (SSD) 1% cream. Gotu kola cream also seems to reduce dryness, itching, irritation, and scar severity when compared with SSD (97027). Other research in adults with second degree burns shows that applying a gauze dressing containing gotu kola 5% and aloe 2.5%, covered with absorbent cotton wool and changed every 3 days, reduces time to healing by 1.5 days and length of hospital stay by 1.7 days when compared with the use of a gauze dressing containing chlorhexidine acetate 0.5% (97028).
• Venous insufficiency. Oral gotu kola seems to improve symptoms of venous insufficiency. Details: Clinical research shows that taking gotu kola or a specific extract of gotu kola (Centellase) 60-180 mg daily orally for 4-8 weeks seems to improve measures of circulation and decrease symptoms such as edema in patients with venous insufficiency (6887,9786,11063,11064,11066,11070,52894,52909).

POSSIBLY INEFFECTIVE

• Cognitive function. Oral gotu kola does not seem to be beneficial for cognitive function. Details: A meta-analysis of a small number of generally moderate quality clinical trials shows that taking a single dose of gotu kola, alone or in combination with other ingredients, does not improve cognitive function when compared with placebo (105334). In one study, gotu kola was taken in combination with ginkgo and docosahexaenoic acid (DHA) for 4 months by healthy, cognitively intact older adults (52880).
• Radiation dermatitis. Topical gotu kola does not seem to reduce symptoms of radiation dermatitis. Details: Clinical research in females undergoing radiotherapy for breast cancer shows that applying a cream containing gotu kola extract 7% once daily during and up to 4 weeks following radiotherapy does not reduce the severity of dermatitis when compared with no treatment or applying a moisturizing cream (102792).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Oral gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy, middle-aged females shows that applying a topical emulsion containing extracts of gotu kola 3% and Indian gooseberry 3% twice daily for 60 days improves skin hydration, some measures of skin wrinkles, and elasticity of the cheek (but not the eye) when compared with placebo (111571). It is unclear if these effects are due to gotu kola, Indian gooseberry, or the combination.
• Alzheimer disease. Although there is interest in using oral gotu kola for Alzheimer disease, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Anal fissures. It is unclear if topical gotu kola is beneficial for anal fissures. Details: In patients with chronic anal fissures who are using standard dietary and hygiene treatments, preliminary clinical research shows that taking gotu kola extract 60 mg twice daily for 8 weeks and locally applying an ointment containing gotu kola does not reduce the mean time to bleeding cessation when compared with standard treatments alone. However, pain may be modestly improved. Also, gotu kola was less effective than an unspecified flavonoid mixture used both orally and topically (105332).
• Atherosclerosis. It is unclear if oral gotu kola is beneficial for slowing the progression of atherosclerotic plaques. Details: Some preliminary clinical research shows that taking gotu kola extract 60 mg orally three times daily for 12 months helps stabilize low-density atherosclerotic plaques when compared with placebo (11062,11069). Gotu kola has also been evaluated in combination with a specific maritime pine bark product (Pycnogenol, Horphag Research). A non-randomized clinical trial shows that taking gotu kola 225 mg and Pycnogenol 150 mg in two divided doses daily for 3 months reduces plaque height and length and increases plaque echogenicity and stability when compared to control (97030). Another non-randomized clinical study in adults with atherosclerotic plaques and no other cardiovascular risk factors shows that taking gotu kola extract 100 mg and Pycnogenol 100 mg daily for up to 4 years reduces plaque progression and increases plaque echogenicity when compared with Pycnogenol alone or no treatment at all. Taking gotu kola and Pycnogenol is also associated with a reduced rate of clinical vascular events, including angina, myocardial infarction, minor transient ischemic attacks (TIAs), and minor strokes when compared with taking Pycnogenol alone or receiving no treatment at all (97029). It is unclear how these outcomes would compare to the use of gotu kola alone.
• Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral gotu kola for ADHD, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Atopic dermatitis (eczema). Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying an ointment containing 5% each of the extracts of heart's ease, gotu kola, and Oregon grape twice daily for 4 weeks does not improve eczema when compared with a base cream. However, patients with eczema on skin exposed to cold weather might experience some improvement (67372).
• Depression. Although there is interest in using oral gotu kola for depression, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Diabetic foot ulcers. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with deep diabetic foot ulcers, preliminary clinical research shows that applying a cream (WH-1 cream) containing 1.25% of gotu kola and Plectranthus amboinicus extracts in a 4:1 ratio twice daily for 2 weeks after surgical debridement is as effective as the use of a standard hydrocolloid fiber wound dressing for improving wound size. However, when compared with baseline, changes in wound size were not statistically significant (105335).
• Diabetic microangiopathy. It is unclear if oral gotu kola is beneficial for diabetic microangiopathy. Details: Preliminary clinical research shows that taking gotu kola extract 60 mg orally twice daily for 6-12 months helps increase measures of circulation and decrease edema in patients with diabetic microangiopathy (11065,11068,52917).
• Dry skin. It is unclear if topical gotu kola is beneficial for dry skin. Details: In patients with dry skin associated with type 2 diabetes, clinical research shows that topical application with 0.25 grams of a gotu kola 1% ointment twice daily, either alone or with oral gotu kola 1100 mg twice daily, for 28 days does not improve dry skin when compared with placebo. However, in a sub-group of patients with well-controlled diabetes, the combination of oral and topical gotu kola modestly improved dry skin (105329). Additionally, a small clinical study in individuals with dry skin due to working with synthetic and natural dyes shows that application of a gotu kola 2% ceramide-based cream to the hands and arms twice daily for 4 weeks improves skin barrier hydration, as measured by hydration of the stratum corneum and skin acidity, when compared to baseline. These improvements were similar to those seen with a ceramide 5% cream (109554). As the gotu kola cream was formulated with ceramide, it is unclear if these findings are due to gotu kola, ceramide, or the combination.
• Epilepsy. Although there is interest in using oral gotu kola for epilepsy, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Generalized anxiety disorder (GAD). It is unclear if oral gotu kola is beneficial for GAD. Details: In patients with GAD, preliminary clinical research shows that taking gotu kola extract 500 mg twice daily for 60 days reduces symptoms of anxiety, depression, and stress by 22% to 26% when compared with baseline (105333). The validity of these findings is limited by the lack of a comparator group.
• Hemorrhoids. It is unclear if topical gotu kola is beneficial for hemorrhoids. Details: Preliminary clinical research in patients with chronic hemorrhoids, as well as patients with acute symptoms following a hemorrhoidectomy or surgical treatment for hemorrhoidal thrombosis, shows that taking gotu kola extract (Centella complex) 60 mg twice daily for 15 weeks and locally applying an ointment (Proctocella) containing gotu kola, arnica, and aloe, in conjunction with standard treatments, does not reduce the mean time to bleeding cessation when compared with standard treatments alone. Anal irritation was modestly improved in the patients with chronic hemorrhoids and in those undergoing treatment for hemorrhoidal thrombosis, but not in those that had undergone a hemorrhoidectomy (105336).
• Herpes zoster (shingles). Although there is interest in using oral gotu kola for shingles, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Hypertension. It is unclear if oral gotu kola is beneficial for hypertension. Details: Preliminary clinical research in patients with hypertension shows that drinking a tea made by boiling gotu kola 4 grams in 250 mL water three times daily for 3 days modestly reduces systolic and diastolic blood pressure when compared with baseline. After consuming the tea, about 40% of patients had normal or high-normal systolic blood pressure and 77% had optimal or normal diastolic blood pressure, compared with 0% and 45%, respectively, prior to consumption (105330). The validity of these findings is limited by the lack of a comparator group.
• Hypertrophic scars. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that topical use of a specific silicone gel (Bangkok Botanica) containing 15% extracts of gotu kola, onion, aloe, and paper mulberry, starting 2 weeks after surgery and continuing for 6 months, moderately improves the height and pliability of the post-surgical hypertrophic scar when compared with a silicone placebo gel. There was no effect on pigmentation or vascularity (102793). It is unknown whether any benefit is related to gotu kola, other ingredients, or their combination.
• Idiopathic interstitial pneumonia. Oral gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small observational registry study in males less than 65 years old with idiopathic interstitial pneumonia has found that taking a specific gotu kola extract (Centellicum; Horphag Research) 225 mg three times daily in combination with a standardized extract of maritime pine bark (Pycnogenol, Horphag Research) 50 mg three times daily for 8 months is associated with a modest improvement in Karnofsky Performance Scale scores and a reduction in fatigue when compared with pirfenidone (108862). However, the validity of these findings is limited by the unblinded, non-randomized nature of the study.
• Keloids. It is unclear if oral or topical gotu kola are beneficial for keloids. Details: There is some early evidence that applying a specific extract of gotu kola (Madecassol) topically might help reduce keloids and hypertrophic scarring (13558). Gotu kola has also been taken orally for keloids. Preliminary clinical research in patients at high risk for keloids shows that taking a specific extract of gotu kola (Centellicum, Horphag Research Ltd) 450 mg daily for 4 weeks starting on the second week after surgery seems to improve scar homogeneity and regularity (99756). However, the reliability of these results is limited because patients in this study were not randomized or blinded to different interventions.
• Laser skin resurfacing. It is unclear if topical gotu kola is beneficial for recovery from laser skin resurfacing. Details: A small clinical trial shows that applying a gel containing gotu kola extract (ECa 233) 0.05% four times daily for 7 days, then twice daily for 3 months, improves wound healing following laser resurfacing for facial acne. Redness returned to baseline levels by day 7, in contrast to day 28 on the side treated with a placebo gel. The general wound appearance and crusting were also improved on the side on which the gotu kola extract gel was applied (102794).
• Osteoarthritis. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large, single-blind clinical study in adults with knee osteoarthritis causing moderate pain shows that applying a specific cream (TMP-4) containing extracts of gotu kola leaf, sesame seed, soybean, and mangosteen peel four times daily for 4 weeks provides similar improvement in pain scores when compared with diclofenac 1% gel. Topical TMP-4 cream also seems to improve knee stiffness, stair climbing, and mobility similarly to diclofenac gel. However, patient impression of overall improvement was higher with diclofenac (110128). The validity of this study is limited by inadequate blinding.
• Scarring. It is unclear if topical gotu kola is beneficial for scarring or tenderness from scarring. Details: Preliminary clinical research in patients without a history of keloid formation suggests that applying a specific cream (Alpha Centella, not available in the US) containing gotu kola and Bulbine frutescens extracts twice daily for 6-8 weeks following suture removal might help to reduce scarring (11072). Also, a large clinical study in adults who underwent carpal tunnel release surgery shows that applying gotu kola cream 1% three times daily for 6 months after suture removal marginally improves self-reported scar tenderness pain when compared with control, and modestly improves scarring scores when compared to baseline (112425). However, the interpretation of these findings is limited by patient-reported outcomes and insufficient validity of the scar scoring tool in this population.
• Skin grafts. Although there is interest in using topical gotu kola for skin graft recovery, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Stretch marks (striae gravidarum). It is unclear if oral gotu kola is beneficial for stretch marks; topical gotu kola has only been evaluated in combination with other ingredients. Details: Preliminary clinical research in females with stretch marks shows that taking a specific extract of gotu kola (Centellicum, Horphag Research Ltd) 225 mg three times daily for 6 weeks increases skin thickness, elasticity, and perfusion when compared with a stretch mark minimizer cream (Clarins) and regular control cream (99757). The validity of these results is limited by the fact that patients were not randomized or blinded to the different interventions. Gotu kola has also been evaluated topically in combination with other ingredients. Preliminary clinical research shows that applying a specific mixture of gotu kola, vitamin E, and collagen-elastin hydrolysates in a cream (Trofolastin, not available in the US) daily during the second and third trimesters reduces stretch marks when compared with a placebo cream (13559). Another small clinical study shows that applying a specific mixture of gotu kola, vitamin E, essential fatty acids, hyaluronic acid, elastin, and menthol in an ointment (Verum, not available in the US) helps decrease the formation of stretch marks during pregnancy when compared with placebo (11073). Other preliminary clinical research in patients without previous striae shows that applying a specific formula containing hydroxyprolisilane C, rosehip oil, gotu kola triterpenes, and vitamin E (Velastisa Antiestrías, ISDIN) twice daily, beginning at week 10-14 and continuing throughout pregnancy, decreases the severity of both new and old stretch marks and the incidence of stretch marks when compared with placebo (92507). It is unclear if the effects seen in these studies are due to gotu kola, other ingredients, or the combinations.
• Systemic lupus erythematosus (SLE). Although there is interest in using oral gotu kola for SLE, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Tonsillitis. Although there is interest in using oral gotu kola for tonsillitis, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Venous thromboembolism (VTE). It is unclear if oral gotu kola is beneficial for VTE prevention. Details: Preliminary clinical research shows that gotu kola decreases edema and improves measures of circulation in patients traveling on airplanes for more than 3 hours when compared to a control group receiving no treatment (11067). However, it is unknown if these changes reduce the incidence of clots.
• Wound healing. Although there is interest in using topical gotu kola for wound healing, there is insufficient reliable information about the clinical effects of gotu kola for this purpose.
• Wrinkled skin. It is unclear if topical gotu kola is beneficial for wrinkled skin. Details: Small, low-quality studies in healthy adults suggest that topical formulations of gotu kola extract or the constituent asiaticoside 0.1% or 0.2% applied 1-3 times daily have shown modest benefit for wrinkled skin. Cream or gel formulations were used for 12 weeks for periorbital wrinkles and a lipstick was used for 8 weeks for lip wrinkles. However, the extent of benefit is not clear and meta-analyses are limited to a very small number of studies with varied comparator groups, including placebo, vehicle, tretinoin 0.02%, and Pueraria mirifica extract (106639). More evidence is needed to rate gotu kola for these uses.

(Read more about GOTU KOLA)

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

(Read more about MADDER)

POSSIBLY EFFECTIVE

• Diabetes. Oral Tinospora cordifolia seems to reduce glycated hemoglobin and fasting blood glucose in adults with type 2 diabetes. Details: A meta-analysis of 2 moderate-sized clinical trials in adults with type 2 diabetes shows that taking Tinospora cordifolia extract 500 mg or 1500 mg daily for 9 or 26 weeks, respectively, reduces glycated hemoglobin by 0.5% when compared with no additional medicine. Additionally, meta-analysis of 2 small to moderate-sized clinical trials in adults with type 2 diabetes shows that taking Tinospora cordifolia extract 1500 mg daily for 26 weeks as tablets or as a decoction 5 mL daily for 9 weeks reduces fasting blood glucose by 4 mg/dL when compared with placebo or no additional medicine (111503). However, all studies were conducted in India; it is unclear if these findings can be extrapolated to other geographic locations.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral Tinospora cordifolia extract is beneficial in patients with allergic rhinitis. Details: One small clinical trial in patients with allergic rhinitis shows that taking a specific Tinospora cordifolia aqueous stem extract (Tinofend, Verdure Sciences) 300 mg three times daily for 8 weeks decreases sneezing, as well as nasal itching, discharge, and obstruction, when compared with placebo (15085).
• Asthma. Although there has been interest in using oral Tinospora cordifolia for asthma, there is insufficient reliable information about the clinical effects of Tinospora cordifolia for this purpose.
• Athletic performance. It is unclear if oral Tinospora cordifolia extract is effective for improving athletic performance. Details: One small clinical study in healthy males shows that taking Tinospora cordifolia stem powdered extract 150-300 mg daily for 28 days improves speed during cycling and hand grip strength when compared to baseline; however, these improvements are not significant when compared with placebo (92230).
• Cancer. Although there has been interest in using oral Tinospora cordifolia for cancer, there is insufficient reliable information about the clinical effects of Tinospora cordifolia for this purpose.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral Tinospora cordifolia for COVID-19, there is insufficient reliable information about the clinical effects of Tinospora cordifolia for this purpose.
• Diabetic foot ulcers. It is unclear if oral Tinospora cordifolia is beneficial in patients with diabetic foot ulcers. Details: One small clinical study in patients with diabetic foot ulcers shows that taking Tinospora cordifolia extract (dose unknown), in conjunction with standard treatment, for one month reduces the total number of debridements by 24% and the extent of phagocytosis in the wound when compared with placebo plus standard treatment. However, Tinospora cordifolia does not appear to improve the wound severity, size, or depth when compared with placebo (92227).
• Gout. Although there has been interest in using oral Tinospora cordifolia for gout, there is insufficient reliable information about the clinical effects of Tinospora cordifolia for this purpose.
• Hepatitis. Although there has been interest in using oral Tinospora cordifolia for hepatitis, there is insufficient reliable information about the clinical effects of Tinospora cordifolia for this purpose.
• Hyperlipidemia. Although there has been interest in using oral Tinospora cordifolia for hyperlipidemia, there is insufficient reliable information about the clinical effects of Tinospora cordifolia for this purpose.
• Hypertriglyceridemia. It is unclear if oral Tinospora cordifolia extract is beneficial in patients with hypertriglyceridemia. Details: One small clinical study in patients with hypertriglyceridemia shows that taking Tinospora cordifolia stem extract 3 grams daily for 14 days reduces levels of triglycerides and low-density lipoprotein (LDL) cholesterol by around 170 mg/dL and 25 mg/dL, respectively, while increasing high-density lipoprotein (HDL) cholesterol levels by 12 mg/dL when compared to baseline. Patients in a control group taking metformin saw smaller improvements in these lipid levels, although a statistical comparison between Tinospora cordifolia and metformin was not reported (106846).
• Osteoarthritis. Oral Tinospora cordifolia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in adults with osteoarthritis shows that taking a specific Ayurvedic formulation (shunthi-guduchi) containing Tinospora cordifolia 440 mg, Indian gooseberry 1000 mg, and ginger 200 mg, with or without Boswellia serrata 600 mg, in divided doses daily for 24 weeks improves pain and functionality as effectively as celecoxib or glucosamine sulfate (89557). However, the clinical validity of these results is limited by the lack of a placebo control. Also, it is unclear if these findings are due to Tinospora cordifolia, other ingredients, or the combination.
• Peptic ulcers. Although there has been interest in using oral Tinospora cordifolia for peptic ulcers, there is insufficient reliable information about the clinical effects of Tinospora cordifolia for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral Tinospora cordifolia for RA, there is insufficient reliable information about the clinical effects of Tinospora cordifolia for this purpose.
• Scabies. It is unclear if topical Tinospora cordifolia lotion is beneficial in patients with scabies. Details: One small clinical study in children and young adults shows that topical application of Tinospora cordifolia lotion 3 days weekly for 2 weeks is as effective as permethrin 5% lotion for clearing the symptoms of scabies. At 28 days from the initiation of treatment, complete cure occurs in 70% of patients applying Tinospora cordifolia, compared with 50% of patients applying permethrin (92220).
• Sexual desire. Although there has been interest in using oral Tinospora cordifolia for increasing sexual desire, there is insufficient reliable information about the clinical effects of Tinospora cordifolia for this purpose. More evidence is needed to rate Tinospora cordifolia for these uses.

(Read more about TINOSPORA CORDIFOLIA)

POSSIBLY SAFE ...when used appropriately in healthy individuals. Asparagus racemosus 500 mg daily has been used with apparent safety for 8 weeks in male recreational athletes (106413).

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

(Read more about ASPARAGUS RACEMOSUS)

POSSIBLY SAFE ...when taken orally in doses of up to 2 grams daily for up to 3 months (3924,3928,41180,41186,41224,41287,41294,41318,98846,107946). There is insufficient reliable information available about the safety of chanca piedra when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used during pregnancy or in those trying to become pregnant. Animal research shows that chanca piedra, particularly at high doses, may have contraceptive effects or may increase the risk of low birth weight or birth defects (41183,41316,41317); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about CHANCA PIEDRA)

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

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

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

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

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

(Read more about FENNEL)

POSSIBLY SAFE ...when used topically and appropriately. Gotu kola has been used safely in a cream or ointment for up to 10 weeks (11072,11073,67372,102792,105329,105335). An emulsion containing gotu kola extract 3% and other ingredients has been applied safely to the skin twice daily for up to 60 days (111571). ...when used orally and appropriately. Gotu kola extract has been used with apparent safety in doses of up to 180 mg daily for up to 12 months or 1000 mg daily for 60 days. Dried gotu kola has been used with apparent safety in doses of up to 2200 mg daily for 4 weeks (6887,11062,11063,11064,11065,11066,11067,11068,11069,11070)(11071,99756,99757,99758,105329,105332,105333). A specific gotu kola extract (Centellicum, Horphag Research Ltd) 450-675 mg daily has been used with apparent safety for up to 6 weeks (99756,99757).

PREGNANCY: POSSIBLY SAFE
when used topically and appropriately (11073,13559). There is insufficient reliable information available about the safety gotu kola when used orally during pregnancy; avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about GOTU KOLA)

LIKELY UNSAFE ...when used orally. It is potentially carcinogenic and mutagenic (2,18,19). There is insufficient reliable information available about the safety of madder when used topically.

PREGNANCY: UNSAFE
when used orally because it may be a potential menstrual stimulant and a genotoxin (2,19).

LACTATION: UNSAFE
when used orally because it is a potential genotoxin (2,19). It also can cause red-colored breast milk (2).

(Read more about MADDER)

POSSIBLY SAFE ...when the stem extract is used orally and appropriately, short-term. Tinospora cordifolia aqueous stem extract has been used with apparent safety at a dose of 900 mg daily for up to 8 weeks (15085). Powdered stem extract has also been used with apparent safety at a dose of up to 3 grams daily for up to 2 weeks or a dose of 1500 mg daily for up to 26 weeks (92230,106846,111503). There is insufficient reliable information available about the safety of other parts of Tinospora cordifolia when used orally or when any part of the plant is used topically.

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

(Read more about TINOSPORA CORDIFOLIA)

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, asparagus racemosus root might increase diuresis and electrolyte loss when used with diuretic drugs.  Details Animal studies show that asparagus racemosus root has diuretic effects when used in high doses (106417). This effect has not been reported in humans.

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, Asparagus racemosus root could reduce excretion and increase levels of lithium.  Details Animal research suggests that Asparagus racemosus root has diuretic properties when used in high doses (106417). Therefore, it might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

(Read more about ASPARAGUS RACEMOSUS)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, chanca piedra might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs.  Details In vitro research suggests that methyl brevifolincarboxylate, a constituent isolated from chanca piedra, can inhibit platelet aggregation (41234). This effect has not been reported in humans.

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, concomitant use with antidiabetes drugs might affect glucose control and increase the risk of hypoglycemia.  Details Animal research suggests that chanca piedra can have hypoglycemic effects (19,41226,41280,41305,41306,41307). However, a small clinical study in adults with diabetes shows that chanca piedra extract 25 grams orally daily for 1 week does not lower fasting or postprandial blood glucose levels (41186).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, concomitant use of chanca piedra with antihypertensive drugs might have additive blood pressure lowering effects.  Details Animal research suggests that chanca piedra can decrease blood pressure (41245). However, this effect was not observed in most hypertensive patients treated with chanca piedra for 10 days (3928).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of chanca piedra with diuretics might increase diuresis.  Details Some preliminary clinical research in adults with hypertension shows that chanca piedra has diuretic properties (3928). However, higher quality research in adults with kidney stones shows taking chanca piedra does not increase urine volume when compared with placebo (41202). Until more is known, use cautiously in patients taking diuretic drugs.

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, chanca piedra might reduce excretion and increase levels of lithium.  Details Some preliminary clinical research in adults with hypertension shows that chanca piedra has diuretic properties (3928). However, higher quality research in adults with kidney stones shows that taking chanca piedra does not increase urine volume when compared with placebo (41202). Until more is known, use cautiously in patients taking lithium. The dose of lithium might need to be decreased.

NOREPINEPHRINE (Levophed) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, chanca piedra may reduce the effects of norepinephrine.  Details Animal research suggests that methyl brevifolincarboxylate, a constituent isolated from chanca piedra, can reverse blood vessel contraction caused by norepinephrine (41215).

(Read more about CHANCA PIEDRA)

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

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

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

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

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

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

(Read more about FENNEL)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking gotu kola might increase the sedative effects of CNS depressants.  Details In vitro research suggests that gotu kola may have sedative effects via binding of GABA receptors (6887,11071).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking gotu kola with hepatotoxic drugs might have additive adverse effects.  Details There are at least four case reports of hepatotoxicity associated with the use of gotu kola. However, more information is needed to determine if gotu kola was the causative factor in these cases (13182,92506).

(Read more about GOTU KOLA)

(Read more about MADDER)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = A Theoretically, Tinospora cordifolia might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Clinical research in adults with type 2 diabetes shows that Tinospora cordifolia can reduce fasting blood glucose and glycated hemoglobin (111503). Additionally, animal research shows that Tinospora cordifolia has hypoglycemic effects (15079,15080,15082,15083,106847).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Tinospora cordifolia might increase levels of drugs metabolized by CYP1A2.  Details In vitro research shows that Tinospora cordifolia extract inhibits CYP1A2 at high concentrations (98225). However, 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, Tinospora cordifolia might increase levels of drugs metabolized by CYP2C19.  Details In vitro research shows that Tinospora cordifolia extract inhibits CYP2C19 at high concentrations (98225). However, 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, Tinospora cordifolia might increase levels of drugs metabolized by CYP2C9.  Details In vitro research shows that Tinospora cordifolia extract inhibits CYP2C9. Animal research shows that Tinospora cordifolia extract 400 mg/kg twice daily for 14 days reduces the clearance and increases plasma levels of glyburide, a CYP2C9 substrate (98225). However, 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, Tinospora cordifolia might increase levels of drugs metabolized by CYP2D6.  Details In vitro research shows that Tinospora cordifolia extract inhibits CYP2D6 at high concentrations (98225). However, this interaction has not been reported in humans.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Tinospora cordifolia might reduce the effectiveness of immunosuppressants.  Details In vitro and animal research shows that Tinospora cordifolia has immunostimulant effects (15081,15086,15089).

(Read more about TINOSPORA CORDIFOLIA)

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

(Read more about ASPARAGUS RACEMOSUS)

General ...Orally, chanca piedra seems to be well tolerated. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Abdominal pain, nausea, vomiting.

Gastrointestinal ...Orally, use of chanca piedra can cause abdominal pain, nausea, and vomiting (99849,107946).

Ocular/Otic ...Orally, chanca piedra was associated with cases of visual impairment in one clinical trial (107946).

Other ...Orally, chanca piedra was associated with cases of fatigue in one clinical trial (107946).

(Read more about CHANCA PIEDRA)

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

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

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

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

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

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

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

(Read more about FENNEL)

General ...Orally and topically, gotu kola seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastric irritation and nausea.
Topically: Eczema.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity.

Dermatologic ...Topically, gotu kola may cause eczema (10277,10278). Also, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (4,6887,9789,52875,52887,52896,52902). One specific gotu kola product (Blasteostimulina,Almirall, S. A.) has been reported to cause allergic contact dermatitis. However, not all patients with reactions to this product are sensitive to gotu kola; some patients are sensitive to neomycin, another ingredient in the product (52875). Madecassol ointment (Rona Laboratories Limited) is another gotu kola product that has resulted in allergic contact dermatitis. Controlled testing suggests that this product can cause this adverse effect in about 8% of patients (9789). Centellase cream has also caused allergic contact dermatitis in at least two cases (52887,52888).

Gastrointestinal ...In some patients, gotu kola can extract cause gastrointestinal upset and nausea (780,6887,52894).

Hepatic ...There is concern that gotu kola may cause liver toxicity in some patients. There are at least four case reports of hepatotoxicity associated with gotu kola; however, hepatotoxic contaminants cannot be ruled out, as laboratory analysis was not conducted on the products used. Additionally, the doses of gotu kola used in these cases were not reported (13182,92506). In a clinical trial where liver function was monitored, taking gotu kola 120 mg daily for 6 months was not associated with changes in liver function (11065).
In one case of hepatotoxicity, a 61-year-old female developed elevated liver transaminase and total bilirubin levels after taking gotu kola tablets for 30 days. Liver biopsy showed granulomatous acute hepatitis. Months later, the patient took gotu kola again and developed elevated liver transaminases after 2 weeks. In another case, a 52-year-old female developed symptoms of hepatitis and increased liver transaminases after taking gotu kola for 3 weeks. Biopsy indicated chronic hepatitis and granulomas, areas of necrosis, and cirrhotic transformation. Liver function normalized after discontinuation of gotu kola. In a third case, a 49-year-old female developed symptoms of hepatitis after taking gotu kola for 2 months. Biopsy revealed granulomatous hepatitis. Liver function normalized after discontinuation of gotu kola (13182). In a fourth case, a 15-year-old female taking an unknown dose of gotu kola and lymecycline for 6 weeks for acne experienced acute liver failure with abdominal pain and vomiting, as well as elevated liver transaminases, bilirubin, international normalized ratio (INR), and prothrombin. Liver function returned to normal after both products were discontinued (92506).

Immunologic ...Topically, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (4,6887,9789,52875,52887,52896,52902). One specific gotu kola product (Blasteostimulina, Almirall, S. A.) has been reported to cause allergic contact dermatitis in some patients. However, not all patients who react to this product are sensitive to gotu kola; some are sensitive to neomycin, another ingredient in the product (52875). Madecassol ointment (Rona Laboratories Limited) is another gotu kola product that has resulted in allergic contact dermatitis. Controlled testing suggests that this product can cause this adverse effect in about 8% of patients (9789). Centellase cream has also caused allergic contact dermatitis in at least two cases (52887,52888).

Psychiatric ...A case of night eating syndrome has been reported for a 41-year-old female who had been taking a gotu kola tincture (dose not specified) for 2 years. Symptoms resolved after gotu kola use was discontinued (52878).

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General ...There is currently a limited amount of information available about the adverse effects of madder. Orally, madder can cause red colored urine, saliva, and perspiration (2). There is some concern that madder can stain contact lenses. Advise patients to be cautious (6002).
Topically, contact dermatitis has been reported while handling madder (20044).

Dermatologic ...Orally, madder can cause red-colored perspiration (2).

Gastrointestinal ...Orally, madder can cause red-colored saliva (2).

Genitourinary ...Orally, madder can cause red-colored urine (2).

Immunologic ...A case of contact dermatitis has been reported in a woman who handled madder while working in the garden (20044).

Ocular/Otic ...There is some concern that madder can stain contact lenses (6002).

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General ...Orally, Tinospora cordifolia seems to be well tolerated. Topically, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Headache and nasal pain.
Topically: Burning, erythema, and pruritus.
Serious Adverse Effects (Rare):
Orally: Liver injury has been reported.

Dermatologic ...Topically, Tinospora cordifolia has been reported to cause pruritus, erythema, and burning (92220).

Hepatic ...Orally, liver injury is reported after consumption of Tinospora cordifolia. In 2 case series, autoimmune hepatitis, acute hepatitis, worsening of chronic liver disease, or acute liver failure is reported in 49 patients after consuming various forms and doses of Tinospora cordifolia alone or in combination with other ingredients for a median of 42-90 days. Of these patients, 2 required a liver transplant and 4 died (110533,110534).
Liver injury is also reported in patients taking combination supplements containing Tinospora cordifolia. One case reports a 50-year-old female who presented with a 2-week history of constant right upper quadrant abdominal pain, nausea, loss of appetite, and fatigue, along with severely elevated alanine transaminase (ALT) and aspartate aminotransferase (AST), after taking a specific combination product containing Tinospora cordifolia 900 mg, stinging nettle 600 mg, and quercetin 600 mg (HistaEze) daily for 4 to 5 weeks (112404). Another case reports a 54-year-old female who developed acute hepatitis with elevated ALT, AST, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin after consuming a multi-ingredient product containing approximately 1900 mg of Tinospora cordifolia and 11 other Ayurvedic herbals daily for 2.5 months (112405). In both cases, liver function returned to normal within 3 months of discontinuing the supplement (112404,112405). It is unclear whether the liver injury in these cases is due to Tinospora cordifolia, other ingredients, or the combination.

Neurologic/CNS ...Orally, Tinospora cordifolia has been reported to cause headache in a clinical trial (15085).

Pulmonary/Respiratory ...Orally, Tinospora cordifolia extract has been reported to cause nasal pain in a clinical trial (15085).

(Read more about TINOSPORA CORDIFOLIA)