Pitta Digest [Discontinued] by Banyan Botanicals

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

Amenorrhea. Although there has been interest in using oral cassia cinnamon for amenorrhea, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
Angina. Although there has been interest in using oral cassia cinnamon for angina, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
Common cold. Although there has been interest in using oral cassia cinnamon for the common cold, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
Diabetes. Several clinical trials have evaluated oral cassia cinnamon for type 2 diabetes, but results are conflicting. Details: Some clinical studies and meta-analyses of cassia cinnamon have found significant benefits in patients with diabetes (11347,17011,21914,21918,89646,89649,111692), while others have not (14344,16010,17689,21915,21916,89650). Results from meta-analyses are also mixed with respect to lowering fasting blood glucose and lipid levels (89647,108264). Meta-analyses including more than 1500 adults with type 2 diabetes show that taking cassia cinnamon 120 mg To 14.4 grams daily for 4-18 weeks reduces fasting blood glucose by an average of 25 mg/dL, total cholesterol by 16 mg/dL, low-density lipoprotein (LDL) cholesterol by 9 mg/dL, and triglycerides by 30 mg/dL, and increases high-density lipoprotein (HDL) cholesterol by 2 mg/dL (89647,111692). Analyses included studies examining either extract or powder, and two of the studies included used an unspecified type of cinnamon. In contrast, a more recent meta-analysis of studies limited to cassia cinnamon ground bark powder 1-2 grams daily for 40-90 days shows no benefit on fasting blood glucose or lipid levels (108264). Evidence regarding cassia cinnamon's effect on glycated hemoglobin (HbA1c) is mixed, with one meta-analysis of 15 clinical studies suggesting that it moderately lowers HbA1c, while other studies suggest that it does not, although some of the studies were too short to detect a change (89647,108264,111692). One meta-analysis found that cassia cinnamon was most beneficial for adults with HbA1c of 8% or higher (111692). The individual studies included in the meta-analyses were also small, and very heterogenous in relation to dose, duration, use of conventional medications, and diabetes control at baseline (89647,108264). Cassia cinnamon has also been evaluated in combination with other ingredients. A study in treatment-naïve adults newly diagnosed with type 2 diabetes shows that taking a combination product containing cassia cinnamon extract 100 mg, black seed extract, and ficin extract (NW Low-Glu) 4-5 times daily for 12 weeks reduces HbA1c by 0.6-0.8% and 2-hour postprandial glucose by 25-35 mg/dl when compared to baseline, with similar findings when compared with metformin. However, there were no notable differences in fasting blood glucose, insulin resistance, and beta cell function (111710). It is unclear if these effects are due to cassia cinnamon, other ingredients, or the combination. In patients with type 1 diabetes, clinical research shows that taking cassia cinnamon daily does not improve fasting blood glucose, HbA1c, insulin sensitivity, or the rate of hypoglycemic episodes (16010,89648).
Diarrhea. It is unclear if oral cassia cinnamon is beneficial for diarrhea. Details: A moderate-sized clinical study in adults with diarrhea shows that taking cinnamon water extract 1200 mg twice daily for 8 weeks increases colonic transit time by about 10 hours but does not improve other symptoms of diarrhea including percentage of bowel movements with diarrhea, Bristol stool scale score, abdominal pain, bowel urgency, or abdominal distension when compared with placebo (111712).
Dyslipidemia. It is unclear if oral cassia cinnamon is beneficial for dyslipidemia. Details: A meta-analysis of 12 clinical studies in adults with metabolic syndrome, polycystic ovary syndrome (PCOS), nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, prediabetes, and overweight or obesity shows that taking cassia cinnamon daily for 2-4 months reduces total cholesterol by 7 mg/dL, triglycerides by 9 mg/dL, and low-density lipoprotein (LDL) cholesterol by 6 mg/dL but does not increase high-density lipoprotein (HDL) cholesterol. Subgroup analysis suggests that cassia cinnamon improves lipid profiles of Asian patients but not European or American patients. Additionally, higher doses appear to regulate lipid profiles better, and cassia cinnamon doses above 1.5 grams daily increase high-density lipoprotein cholesterol by about 2.5 mg/dL. Subgroup analysis also shows that cassia cinnamon only reduces triglycerides for patients with metabolic syndrome and increases HDL cholesterol for patients with PCOS but does not impact total cholesterol for those with type 2 diabetes (111709).
Erectile dysfunction (ED). Although there has been interest in using oral cassia cinnamon for ED, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
Hypertension. Although there has been interest in using oral cassia cinnamon for hypertension, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
Impaired glucose tolerance (prediabetes). The effects of cassia cinnamon in patients with impaired glucose tolerance are unclear; results from clinical research are conflicting. Details: A small clinical study in patients with impaired glucose tolerance shows that taking cassia cinnamon powder 6 grams twice daily for 12 weeks does not improve fasting plasma glucose or insulin sensitivity when compared with placebo (96280). However, another clinical study in overweight or obese patients with impaired fasting blood glucose shows that taking a dried aqueous extract of cassia cinnamon 250 mg twice daily for 12 weeks reduces fasting blood glucose by about 12 mg/dL when compared with baseline, but does not affect fasting insulin levels (93118). Another preliminary clinical trial in overweight or obese patients with impaired glucose tolerance shows that taking two capsules of a specific combination product, (Glycabiane, PiLeJe) containing cassia cinnamon extract 228 mg, chromium chloride 10 mcg, and carnosine 100 mg per capsule, daily for 4 months decreases fasting blood glucose by 6.5 mg/dL but has no effect on glycated hemoglobin (HbA1c), insulin sensitivity, or body weight, when compared with placebo (94234). It is unclear whether these effects are due to cassia cinnamon, ingredients, or the combination.
Mosquito repellent. It is unclear if topical cassia cinnamon is beneficial as a mosquito repellent. Details: Preliminary clinical research suggests that applying a cream containing cassia cinnamon oil 5% to the skin provides protection from mosquito bites. However, the repellency of this cream appears to decrease more quickly over time compared to MeiMei cream (containing citronella and geranium oils) and Repellan S aerosol (containing 19% N,N-diethyl-m-toluamide (DEET)) (59580).
Muscle cramps. Although there has been interest in using oral cassia cinnamon for muscle cramps, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
Nausea and vomiting. Although there has been interest in using oral cassia cinnamon for nausea and vomiting, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose.
Obesity. It is unclear if oral cassia cinnamon is beneficial for weight loss. Details: A meta-analysis of 7 clinical studies shows that cassia cinnamon reduces body mass index (BMI) when compared with placebo (111692). However, preliminary clinical research in a small number of patients with overweight or obesity and impaired glucose tolerance shows that taking two capsules of a specific combination product (Glycabiane, PiLeJe) containing cassia cinnamon extract 228 mg, chromium chloride 10 mcg, and carnosine 100 mg per capsule, daily for 4 months does not decrease body weight, BMI, fat mass, or lipid levels when compared with placebo (94234). A very small clinical study in healthy adults shows that drinking a single dose of cinnamon infusion containing 2 grams of powdered cinnamon served along with breakfast does not increase energy expenditure, diet-induced thermogenesis, respiratory quotient, or lipid and carbohydrate oxidation and does not affect appetite responses including hunger, fullness, desire to eat, macronutrient intake, and food intake throughout the day when compared with control. Furthermore, cassia cinnamon intake reduces feelings of satiety and increases energy intake in the first meal after the intervention when compared with control (111707). The validity of these findings is limited by a lack of blinding.
Polycystic ovary syndrome (PCOS). It is unclear if oral cassia cinnamon is beneficial for patients with PCOS. Details: A small observational study in adults with PCOS suggests that taking cinnamon 500 mg three times daily for 8 weeks is associated with decreased body weight, body mass index, insulin resistance, and testosterone but does not appear to alter levels of luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone (DHEA), insulin, or lipids when compared with placebo (113514).
Stroke. It is unclear if oral cassia cinnamon is beneficial for stroke prevention. Details: Preliminary clinical research in patients with a mild ischemic stroke or transient ischemic attack shows that taking cinnamon (Chinese herbal formula granules, Guangdong Yifang Pharmaceutical Co, Ltd) 5 grams with aspirin 100 mg daily for 90 days, starting within 24 hours of the ischemia, reduces the percentage of patients with a recurrent stroke to 3%, compared with 15% of those taking aspirin plus placebo. There were also modest improvements in levels of plasma lipids, glucose, and glycated hemoglobin, as well as a reduced likelihood of identifying unstable or severe plaques on carotid ultrasound (108265). The use of cassia cinnamon, specifically, was not confirmed; however, this species of cinnamon is commonly used in traditional Chinese medicine, as indicated in the study.
Urinary incontinence. Although there has been interest in using oral cassia cinnamon for urinary incontinence, there is insufficient reliable information about the clinical effects of cassia cinnamon for this purpose. More evidence is needed to rate cassia cinnamon for these uses.

CELERY

Anxiety. It is unclear if oral celery seed extract is beneficial in patients with anxiety. Details: A small clinical study in Iranian adults with hypertension on standard antihypertensive therapy shows that taking celery seed extract 1.34 grams daily for 4 weeks reduces symptoms of anxiety and depression when compared with placebo (112409). However, it is unclear if these benefits can be extrapolated to patients in geographic locations other than Iran.
Depression. It is unclear if oral celery seed extract is beneficial in patients with depression. Details: A small clinical study in Iranian adults with hypertension on standard antihypertensive therapy shows that taking celery seed extract 1.34 grams daily for 4 weeks reduces symptoms of anxiety and depression when compared with placebo (112409). However, it is unclear if these benefits can be extrapolated to patients in geographic locations other than Iran.
Diabetes. It is unclear if oral celery seed extract is beneficial in patients with diabetes. Details: A small clinical study in adults with type 2 diabetes shows that taking celery seed powder 250 mg three times daily for 12 weeks does not improve fasting blood glucose, fasting insulin, insulin resistance, total cholesterol, low-density lipoprotein or high-density lipoprotein cholesterol, triglycerides, or blood pressure when compared with placebo (112411). However, the study may have been inadequately powered to detect a difference between groups.
Dysmenorrhea. Oral celery seed has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical trial in female college students shows that taking a specific combination product containing celery seed, saffron, and anise extracts (SCA, Gol Daro Herbal Medicine Laboratory) 500 mg three times daily for 3 days, starting at the beginning of bleeding or pain, reduces severity and duration of pain symptoms associated with menstruation when compared with placebo (17214). It is not clear if these effects are due to celery, other ingredients, or the combination.
Dyspepsia. Oral celery seed has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical trial in adults with functional dyspepsia conducted in Iran shows that taking celery seed powder 500 mg daily with bishop's weed 500 mg daily spread over three doses after meals for 4 weeks reduces patient-reported dyspepsia symptom severity when compared with domperidone. Taking celery and bishop's weed also reduces patient-reported symptom frequency when compared to baseline (112410). However, it is unclear if these effects are due to celery, bishop's weed, or the combination, or if results can be extrapolated to patients in geographic locations other than Iran. The interpretation of these results is also limited by the lack of a placebo group.
Gout. Oral celery has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small, open-label clinical study in patients with gout shows that taking a specific combination product (GoutFigher, Max Biocare) containing celery seed extract 600 mg, devil's claw root extract 300 mg, sour cherry extract 200 mg, and other ingredients twice daily for 45 days reduces pain, joint inflammation, and uric acid levels when compared to baseline (106488). The validity of these findings is limited by the lack of a control group. Additionally, it is unclear if these findings are due to celery, other ingredients, or the combination.
Headache. Although there has been interest in using oral celery for headache, there is insufficient reliable information about the clinical effects of celery for this purpose.
Hypertension. It is unclear if oral celery seed extract is beneficial in patients with hypertension. Details: A small clinical study in Iranian adults with hypertension on standard antihypertensive therapy shows that taking celery seed extract 1.34 grams daily for 4 weeks reduces daytime systolic blood pressure by about 12 mmHg compared to less than 1 mmHg with placebo. Celery seed extract also reduces night-time blood pressure, diastolic blood pressure, and mean arterial pressure, but does not impact the heart rate (110755). However, it is unclear if these benefits can be extrapolated to patients in geographic locations other than Iran.
Impaired glucose tolerance (prediabetes). It is unclear if oral celery leaf extract is beneficial in patients with prediabetes. Details: A small clinical study in elderly patients with prediabetes shows that taking celery leaf extract 250 mg three times daily for 12 days reduces postprandial plasma glucose levels, but not insulin levels, when compared to baseline (99572). Although a control group was included in the study, statistical comparisons between treatment and control groups were not reported.
Mosquito repellent. It is unclear if topical celery seed extract is beneficial for use as a mosquito repellant. Details: One small clinical study shows that applying gel formulations containing celery seed extract 5% to 25% can repel mosquitos in a dose-dependent manner for up to 4.5 hours. These formulations show similar repellant action when compared with DEET-containing formulations and appear to be superior to commercial repellants without DEET (40988). Celery extract has also been evaluated in combination with other ingredients. Two clinical studies show that application of a specific formulation (G10, E.A.R. Samunpri) containing celery seed extract 5%, along with vanillin, eucalyptus oil, orange oil, and citronella oil, seems to repel mosquitos for up to 4.5 hours comparably to other commercial products, including DEET 25% and Insect Block 28 (41049,41052). It is unclear if these findings are due to celery, other ingredients, or the combination.
Osteoarthritis. Oral celery seed has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small, open-label clinical study in patients with mild knee osteoarthritis shows that taking a specific combination product (Tregocel, Max Biocare) providing celery seed 1000 mg, Boswellia serrata resin extract 1000 mg, devil's claw 1000 mg, ginger rhizome 330 mg, and curcumin 180 mg daily for 36 weeks reduces pain, improves functional capacity, and increases walking distance when compared to baseline (106078). The validity of these findings is limited by the lack of a control group. Additionally, it is unclear if these findings are due to celery, other ingredients, or the combination.
Rheumatoid arthritis (RA). Although there has been interest in using oral celery juice for RA, there is insufficient reliable information about the clinical effects of celery for this purpose.
Sexual dysfunction. It is unclear if oral celery seed powder is beneficial in females with sexual dysfunction. Details: One small clinical study in females with sexual dysfunction shows that taking celery seed powder 500 mg three times daily for 6 weeks improves sexual dysfunction symptom scores, primarily due to patient-rated improvements in sexual desire, arousal, lubrication, and pain, when compared with placebo (106486).
Urinary tract infections (UTIs). Although there has been interest in using oral celery juice for UTIs, there is insufficient reliable information about the clinical effects of celery for this purpose. More evidence is needed to rate celery for these uses.

CORIANDER

Anorexia. Although there has been interest in using oral coriander to stimulate appetite in patients with anorexia, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Anxiety. Although there has been interest in using oral coriander for anxiety, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Constipation. Oral coriander has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in nursing home residents with constipation shows that taking one cup of a specific tea (Smooth Move, Traditional Medicinals) containing senna leaf 1080 mg and 920 mg of a proprietary blend of coriander fruit, licorice root, fennel, orange peel, cassia cinnamon, and ginger daily for 28 days can increase the number of bowel movements when compared with placebo (46196). It is unclear if this effect is due to coriander, other ingredients, or the combination.
Diabetes. Although there has been interest in using oral coriander for diabetes, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Diarrhea. Although there has been interest in using oral coriander for diarrhea, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Dyspepsia. Although there has been interest in using oral coriander for dyspepsia, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Epilepsy. Although there has been interest in using oral coriander for epilepsy, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Flatulence. Although there has been interest in using oral coriander for flatulence, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Insomnia. Although there has been interest in using oral coriander for insomnia, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Intestinal parasite infection. Although there has been interest in using oral coriander for intestinal parasite infection, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Irritable bowel syndrome (IBS). Oral coriander has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with IBS shows that taking 30 drops of a combination product containing total extracts of coriander, lemon balm, and spearmint (Carmint, Pour Sina) three times daily after meals for 8 weeks, in addition to standard treatment with loperamide or psyllium, reduces abdominal pain and discomfort when compared with standard treatment alone (19535). It is unclear if these effects are due to coriander, other ingredients, or the combination.
Lactation. Although there has been interest in using oral coriander to stimulate lactation, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Osteoarthritis. Although there has been interest in using oral coriander for osteoarthritis, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Rheumatoid arthritis (RA). Although there has been interest in using oral coriander for RA, there is insufficient reliable information about the clinical effects of coriander for this purpose.
Skin irritation. It is unclear if oral coriander seed oil is beneficial in patients with skin irritation. Details: A small clinical study in Caucasian females aged 18-65 years with sensitive and reactive skin shows that taking a specific coriander seed oil product (Sepibliss, Seppic Inc.) 200 mg daily for 8 weeks reduces redness and itching after exposure to skin stress tests and improves patient-rated perceptions of skin sensitivity and reactivity when compared with placebo (111131).
Tinea pedis. It is unclear if topical coriander oil is beneficial in patients with tinea pedis. Details: A small clinical study in adults with tinea pedis shows that applying coriander oil 6% ointment (Oleum Coriandri e Semine; Caesar & Loretz GmbH) twice daily to affected areas for 28 days is approximately 20% more effective for eliminating clinical signs of infection, as rated by patients and clinicians, when compared with applying the ointment alone (97874). More information is needed to rate coriander for these uses.

CUMIN

Diabetes. It is unclear if oral cumin is beneficial in patients with diabetes. Details: Two small clinical studies in adults with type 2 diabetes show that taking cumin essential oil 25-100 mg by mouth daily for 8-12 weeks reduces fasting blood glucose, glycated hemoglobin (HbA1c), serum insulin, and diabetes-associated inflammatory markers when compared with placebo (111368,111370). However, meta-analyses of studies in patients with and without type 2 diabetes show conflicting results. One analysis of seven clinical trials shows that taking cumin essential oil 25-300 mg daily for up to 24 weeks does not improve fasting plasma glucose, HbA1c, or other markers of glycemic control when compared with a control group (106516). Another meta-analysis evaluating eight clinical trials, including all seven assessed in the previous analysis, shows that cumin essential oil has a large effect on both fasting plasma glucose and HbA1c when compared with control (106517). These discrepant findings may be due to the inclusion of an additional trial in the second analysis or different methods for pooling study results.
Dyslipidemia. It is unclear if oral cumin is beneficial in patients with dyslipidemia. Details: A meta-analysis of six clinical trials including 376 individuals with or without hyperlipidemia shows that taking cumin reduces levels of total cholesterol by around 11 mg/dL and low-density lipoprotein (LDL) cholesterol by around 7 mg/dL when compared with control or placebo. Cumin also increases high-density lipoprotein (HDL) cholesterol levels by around 3 mg/dL, but does not affect triglyceride levels. A sub-analysis of dosages and dosage forms shows that cumin essential oil 25-100 mg daily or cumin powder 3 grams daily were beneficial, while lower doses of the powder or essential oil and all doses of cumin extract did not affect lipid levels. Patients included in the available research were either overweight or obese or had been diagnosed with type 2 diabetes or non-alcoholic steatohepatitis (NASH) (100162). It is not clear what effect, if any, cumin has in patients with diagnosed dyslipidemia.
Hypertriglyceridemia. Small clinical studies suggest that oral cumin extract or essential oil does not seem to reduce triglyceride levels in patients with hypertriglyceridemia, although it may improve other lipid parameters. Details: A meta-analysis of two small clinical trials in adults with either type 2 diabetes or non-alcoholic steatohepatitis (NASH) who also have hypertriglyceridemia shows that taking cumin extract 225 mg daily for 6 months or cumin essential oil 25 mg daily for 3 months modestly reduces levels of total cholesterol and low-density lipoprotein (LDL) cholesterol and modestly increases levels of high-density lipoprotein (HDL) cholesterol when compared with placebo. However, taking cumin does not improve triglyceride levels (100162).
Impaired glucose tolerance (prediabetes). It is unclear if oral cumin is beneficial in patients with prediabetes. Details: A small clinical trial in adults with prediabetes shows that taking cumin essential oil 75 mg daily for 10 weeks does not improve fasting blood glucose, glycated hemoglobin (HbA1c), or measures of insulin resistance but does seem to reduce body weight, body mass index (BMI), and low-density lipoprotein (LDL) cholesterol and increase high-density lipoprotein (HDL) cholesterol when compared with placebo (111369).
Irritable bowel syndrome (IBS). Although there has been interest in using oral cumin for IBS, there is insufficient reliable information about the clinical effects of cumin for this purpose.
Metabolic syndrome. It is unclear if oral cumin essential oil is beneficial in patients with metabolic syndrome. Details: A small clinical trial in adults with metabolic syndrome shows that taking cumin essential oil 75 mg three times daily for 8 weeks does not improve body weight, blood pressure, glycemic control, or lipid levels when compared with placebo (104143).
Nonalcoholic steatohepatitis (NASH). Although there has been interest in using oral cumin for NASH, there is insufficient reliable information about the clinical effects of cumin for this purpose.
Obesity. Small clinical studies suggest that oral cumin essential oil or powder may reduce body weight and body mass index (BMI) in overweight or obese individuals. Details: One small clinical study in overweight and obese individuals maintaining their usual diet and physical activity shows that taking cumin essential oil 100 mg three times daily for 8 weeks reduces weight by 1.3 kg and BMI by 0.5 kg/m2 when compared with placebo. The effect of cumin was similar to that of orlistat 120 mg three times daily. Cumin, but not orlistat, improved plasma insulin levels and insulin sensitivity; however, it did not affect insulin resistance, thyroid function, or plasma glucose or lipid levels (100160). Another small clinical study in overweight or obese females shows that taking cumin powder 1.5 grams in 150 mL of low-fat yogurt twice daily with meals as part of a calorie-restrictive diet for 3 months increases weight loss by an additional 2 kg when compared with yogurt and a calorie-restrictive diet alone. Intake of cumin also improved BMI, fat mass, waist circumference, and blood lipid levels, but did not affect fasting blood glucose levels (100161). More evidence is needed to rate cumin for these uses.

FENNEL

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.

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.

Dyslipidemia. Oral Indian gooseberry seems to be beneficial for dyslipidemia. Details: Meta-analyses of 12 small clinical studies in healthy adults or patients with dyslipidemia, diabetes, hypertension, or metabolic syndrome show that taking Indian gooseberry fruit extract or powder 0.5-3 grams daily or Indian gooseberry fruit 12 grams daily for 2-12 weeks reduces total cholesterol by around 39 mg/dL, low-density lipoprotein (LDL) cholesterol by around 15-34 mg/dL, and triglycerides by around 22-52 mg/dL when compared with control groups. Results are conflicting whether Indian gooseberry increases high-density lipoprotein (HDL) cholesterol (111567,111568). Subgroup analysis suggests that Indian gooseberry is more effective at doses greater than 1 gram daily and in adults with triglycerides above 150 mg/dL (111568). Clinical research in patients with dyslipidemia shows that taking Indian gooseberry whole fruit extract (Tri-low, Arjuna Natural Ltd.) 500 mg twice daily for 12 weeks reduces triglyceride and low-density lipoprotein (LDL) cholesterol levels by 34% and 20%, respectively, compared with 15% and 5%, respectively, in patients taking placebo (99238).
Gastroesophageal reflux disease (GERD). Oral Indian gooseberry seems to be beneficial for reducing symptoms of GERD. Details: Clinical research in adults who have had non-erosive symptoms of GERD for at least 3 months shows that taking Indian gooseberry fruit extract 1000 mg twice daily for 4 weeks reduces the frequency and severity of heartburn and regurgitation by about 63% and 50%, respectively, compared with reductions of 24% and 5%, respectively, in patients taking placebo (99240).

Aging skin. Oral Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy, middle-aged females shows that drinking 50 mL of a juice containing Indian gooseberry extract 30-60 mg and lingonberry extract 25-50 mg daily for 12 weeks improves skin elasticity, thickness, wrinkles, and hydration when compared with placebo (102856). It is unclear if these effects are due to Indian gooseberry, lingonberry, or the combination. Another small clinical study in healthy, middle-aged females shows that applying a topical emulsion containing extracts of Indian gooseberry 3% and gotu kola 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 Indian gooseberry, gotu kola, or the combination.
Androgenic alopecia. Topical Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In individuals with self-perceived hair loss, preliminary clinical research shows that applying a hair product containing Indian gooseberry modestly improves hair growth rate and density, as well as hair thinning, when compared with baseline. Patients used a leave-in product containing Indian gooseberry (Saberry), coconut water solids (Cococin), gamma-L-glutamyl-selenomethionine (Peptiselect), and other ingredients as 3.5 mL in females and 2 mL in males, once daily for 3 months (105353).
Cancer. Although there is interest in using oral Indian gooseberry for cancer, there is insufficient reliable information about the clinical effects of Indian gooseberry for this purpose.
Cardiovascular disease (CVD). It is unclear if oral Indian gooseberry is beneficial for the prevention of CVD. Details: A meta-analysis of 9 small clinical studies in adults who are healthy or have CVD risk factors shows that taking Indian gooseberry fruit extract or powder 500-1500 mg daily for 2-12 weeks reduces low-density lipoprotein (LDL) cholesterol by around 15 mg/dL, very low-density lipoprotein (VLDL) cholesterol by around 5 mg/dL, triglycerides by around 22 mg/dL, and high-sensitivity C-reactive protein when compared with control groups. However, the meta-analysis suggests that Indian gooseberry does not improve high-density lipoprotein (HDL) cholesterol, systolic blood pressure, or diastolic blood pressure (111567). The validity of these findings is limited by small sample sizes and considerable heterogeneity among the included studies.
Coronavirus disease 2019 (COVID-19). It is unclear if oral Indian gooseberry is beneficial for the treatment of COVID-19 in hospitalized adults. Details: A small clinical trial in adults hospitalized with COVID-19 shows that receiving Indian gooseberry powder 2 grams twice daily for 10 days does not impact RT-PCR positivity rate at day 10 when compared with placebo. Additionally, there were no clear trends in clinical improvement in patients receiving Indian gooseberry when compared with placebo. All patients in this study also received oral hydroxychloroquine and lopinavir/ritonavir (110012).
Diabetes. Several small or limited-quality clinical studies suggest that oral Indian gooseberry may modestly improve glycemic control and blood lipid levels in patients with type 2 diabetes. Details: A moderate-sized, open-label study in adults with newly-diagnosed type 2 diabetes and dyslipidemia shows that taking Indian gooseberry extract, standardized to 10% beta-glucogallin, 2 grams daily for 90 days reduces glycated hemoglobin (HbA1c), fasting blood glucose, and postprandial blood glucose when compared to baseline, with superior effects on fasting blood glucose and postprandial blood glucose when compared with metformin 500 mg (111569). A smaller clinical study in patients with type 2 diabetes on stable doses of metformin shows that taking Indian gooseberry fruit extract (Capros, Natreon Inc) 500 mg twice daily for 12 weeks reduces HbA1c by around 0.5% and improves low-density lipoprotein (LDL) cholesterol, triglyceride, and high-density lipoprotein (HDL) levels when compared with placebo. Taking a lower dose, 250 mg twice daily, does not seem to improve HbA1c but has a modest effect on lipid levels (105356). Another small clinical study in patients with type 2 diabetes using various antidiabetes drugs shows that taking powdered Indian gooseberry fruit 1 gram, 2 grams, or 3 grams daily for 3 weeks modestly reduces fasting and 2-hour postprandial blood glucose levels and improves lipid levels when compared to baseline (105355). The validity of these findings is limited by the lack of a comparator group.
Hangover. It is unclear if oral Indian gooseberry is beneficial for hangover prevention. Details: A small clinical trial shows that taking Indian gooseberry leaf extract (Phyllpro) 750 mg daily for 10 days prior to alcohol intoxication modestly reduces some hangover symptoms 10 hours later, including nausea, headache, lack of appetite, and dizziness, when compared with placebo. Blood alcohol levels after 12 hours were also reduced. However, the overall hangover score was not significantly different between groups (99846).
Hepatitis B. Although there is interest in using oral Indian gooseberry for hepatitis B, there is insufficient reliable information about the clinical effects of Indian gooseberry for this condition.
Hypercholesterolemia. Small studies suggest that oral Indian gooseberry might help to reduce low-density lipoprotein (LDL) cholesterol levels. Details: Preliminary clinical research shows that taking Indian gooseberry might reduce levels of LDL cholesterol in patients with hypercholesterolemia. One preliminary clinical study shows that taking Indian gooseberry 50 grams for 4 weeks decreases LDL cholesterol by 15% when compared to baseline (2077). Other preliminary clinical research shows that taking Indian gooseberry fruit extract (Amlamax, Arjuna Natural Ltd.) 500 mg or 1000 mg daily for 6 months reduces levels of LDL cholesterol by about 13% when compared with baseline (99241). Also, one small study shows that taking an Indian gooseberry fruit juice powder 500 mg daily for 6 weeks modestly decreases LDL cholesterol and triglyceride levels when compared with baseline (99242). Some preliminary clinical research also shows that Indian gooseberry reduces LDL cholesterol in obese individuals. One small study shows that taking Indian gooseberry fruit extract (Capros, Natreon Inc.) 500 mg twice daily for 12 weeks reduces LDL cholesterol by 16 mg/dL in this population when compared to baseline (92515). However, the validity of these studies is limited by the lack of comparator groups.
Hypertension. It is unclear if oral Indian gooseberry is beneficial for hypertension. Details: In patients with uncontrolled hypertension using standard therapies, clinical research shows that taking Indian gooseberry dried fruit powder 500 mg three times daily for 8 weeks reduces systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 16% and 12%, respectively, from baseline, which is significantly greater than reductions seen with placebo. The frequency of response to treatment, based on a reduction in SBP or DBP of at least 10 mmHg or 5 mmHg, respectively, was also increased from up to 50% to at least 83% of patients (105352). However, other clinical research in adults with cardiovascular risk factors shows that taking Indian gooseberry 500-1500 mg twice daily for 2-12 weeks does not reduce SBP or DBP more than placebo (105354,111567).
Irritable bowel syndrome (IBS). Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small, open-label study of adults with IBS shows that taking 7 grams of an Unani medicinal product called Jawarish Shahi, containing Indian gooseberry, terminalia, coriander, cardamom, and willow bark, twice daily for 45 days reduces the severity of IBS, as measured by improvements in abdominal pain and distension, bowel habits, and quality of life, when compared to baseline (111570). The validity of these findings is limited by insufficient blinding and the lack of a comparator group. It is unclear if these effects are due to Indian gooseberry, other ingredients, or the combination.
Metabolic syndrome. It is unclear if oral Indian gooseberry is beneficial for metabolic syndrome. Details: Preliminary clinical research in adults with metabolic syndrome shows that taking a specific Indian gooseberry extract (Capros, Natreon Inc.) 250 mg twice daily for 12 weeks reduces total cholesterol by nearly 10%, low-density lipoprotein (LDL) cholesterol by 15%, and triglycerides by 10%, and increases high-density lipoprotein (HDL) cholesterol by about 7% when compared with placebo. Additionally, taking this product as 500 mg twice daily reduces total cholesterol by 14%, LDL cholesterol by 26%, and triglycerides by 19%, and increases HDL cholesterol by 22% when compared with placebo. Both doses also seem to improve markers of endothelial function, oxidative stress, and systemic inflammation (102857).
Obesity. It is unclear if oral Indian gooseberry is beneficial for improving weight loss or metabolic parameters in adults with obesity. Details: Preliminary clinical research in overweight or obese individuals shows that taking Indian gooseberry fruit extract (Capros, Natreon Inc.) 500 mg twice daily for 12 weeks reduces low-density lipoprotein (LDL) cholesterol by 16 mg/dL when compared to baseline. However, there was no effect on other lipids or on blood pressure, body weight, or body mass index (92515). The validity of these findings is limited by the lack of a comparator group.
Oral mucositis. It is unclear if oral Indian gooseberry is beneficial in patients with radiation-induced mucositis. Details: A retrospective observational study in patients with head and neck cancer receiving radiotherapy suggests that rinsing the mouth with Indian gooseberry 1% and povidone-iodine twice daily is associated with delayed development of mucositis and intolerable mucositis and a decreased incidence of intolerable mucositis when compared with povidone-iodine alone (111566). The validity of these findings is limited by the retrospective study design.
Osteoarthritis. Oral Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with knee osteoarthritis suggests that specific Ayurvedic formulas containing Indian gooseberry may be equivalent to glucosamine sulfate 2 grams daily or celecoxib 200 mg daily for reducing pain. Two capsules containing Indian gooseberry 166.66 mg/capsule, ginger 33.33 mg/capsule, and Tinospora cordifolia 73.33 mg/capsule, with or without Boswellia serrata 100 mg/capsule, taken three times daily for 24 weeks, were used. All four treatments reduced active pain by about 28% to 38%, functional pain by 19% to 29%, and functional difficulty by 18% to 25%, with no significant between-group differences in the observed improvements (89557). It is not clear if these effects are due to Indian gooseberry, the other ingredients, or the combination.
Periodontitis. It is unclear if subgingival Indian gooseberry is beneficial for periodontitis. Details: Clinical research in patients with chronic periodontitis shows that the subgingival application of a sustained-release Indian gooseberry fruit 10% gel following scaling and root planing does not affect plaque or gingivitis development over 2-3 months when compared with placebo. However, there was a modest benefit on periodontal destruction based on probing pocket depth (105358).
Vitiligo. Oral Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with vitiligo shows that taking 1 tablet containing Indian gooseberry 100 mg, vitamin E 10 mg, and carotenoids 4.7 mg orally 3 times daily for 6 months, in combination with conventional topical therapy and/or phototherapy, increases re-pigmentation in the head, neck, and trunk and decreases signs of inflammation when compared with conventional treatment alone (92513). More evidence is needed to rate Indian gooseberry for these uses.

LICORICE

Atopic dermatitis (eczema). Some clinical research suggests that topical licorice seems to improve symptoms of atopic dermatitis. Details: Applying gel formulations containing 1% or 2% licorice root extract three times daily for 2 weeks seems to reduce erythema by 35% to 61%, edema by 57% to 84%, and itching by 44% to 73%. The 2% gel seems to be more effective than the 1% gel (59732).
Canker sores. Some clinical research suggests that topical licorice patches and mouth rinses seems to reduce ulcer size and pain in patients with recurrent aphthous stomatitis. Details: Clinical research shows that applying an oral patch containing licorice 0.015-0.229 mg/kg for 16 hours each day for 8 days does not affect ulcer healing time, but reduces ulcer size and post-stimulus pain, when compared with placebo (59769). A small clinical study also shows that applying bioadhesive hydrogel patches containing 1% licorice extract reduces the pain, as well as the diameter of necrosis and inflammatory halo of recurrent canker sores, when compared to baseline (59781). Mouth rinses containing licorice have also been used. One clinical study shows that swishing a diphenhydramine and 5% licorice extract solution around the mouth for about 3 minutes four times daily until the sores have healed reduces the average time to healing by 1.5 days when compared to a solution containing diphenhydramine alone. Pain was reduced by up to 69% more in those using licorice extract (104564). Another small clinical study shows that gargling with licorice extract four times daily for 2 days has a large beneficial effect on pain and ulcer size when compared with using a placebo gargle. The licorice extract was made by boiling licorice root 40 grams in one liter of water for 30 minutes and cooled (110319). In addition, preliminary clinical research shows that gargling with warm water containing deglycyrrhizinated licorice powder 200 mg four times daily for 7 days improves pain in 75% of patients by day one and results in complete healing in 75% of patients by day three (59857).
Endotracheal intubation-related adverse effects. Some clinical research suggests that using licorice as a gargle or lozenge prior to endotracheal intubation can reduce adverse effects like sore throat and cough. Details: A meta-analysis of 5 clinical trials in patients undergoing elective surgical procedures shows that topical use of licorice, either as a gargle or lozenge, prior to endotracheal intubation reduces the risk for sore throat by 56% and reduces the risk for cough by 39% when compared with a control group at 24 hours post-extubation (100985). One clinical study included in this analysis shows that sucking on a single lozenge (Sualin, Hamdard Pharma) containing licorice extract 97 mg beginning 30 minutes prior to intubation reduces the risk for cough immediately after extubation by 56% when compared with a sugar candy lozenge. However, it doesn't seem to reduce cough at 30 minutes, 12 hours, or 24 hours post-extubation. This lozenge also appears to reduce the risk for sore throat by about 32% at 12 and 24 hours post-extubation, but not immediately or 30 minutes after extubation (25670). Additional clinical studies included in the meta-analysis show that gargling with fluid prepared with licorice 0.5 grams for at least one minute beginning 5 minutes prior to endotracheal intubation reduces the incidence and severity of post-extubation sore throat and coughing when compared with a water control (26464,59793).

Acne. Topical licorice 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 acne associated with mask wearing shows that topical application of a combination of licorice root extract 0.3%, calendula 4%, and snail secretion filtrate 40% (AI complex) to the face twice daily for 12 weeks modestly reduces inflammatory, but not non-inflammatory or total, acne lesions when compared with placebo. There was no difference in overall treatment success, defined as at least almost clear skin or a large improvement (110322). It is unclear if any benefits are due to licorice, other ingredients, or the combination.
Addison disease. Although there has been interest in using oral licorice for Addison disease, there is insufficient reliable information about the clinical effects of licorice for this condition.
Adrenal insufficiency. Although there has been interest in using oral licorice for adrenal insufficiency, there is insufficient reliable information about the clinical effects of licorice for this condition.
Allergic rhinitis (hay fever). It is unclear if using a licorice-containing nasal irrigation suspension improves symptoms in patients with allergic rhinitis. Details: A clinical study in patients with allergic rhinitis shows that using a nasal irrigation suspension containing licorice extract 900 mg daily for 1 month improves symptoms such as nasal blockage, rhinorrhea, sneezing, postnasal discharge, and olfactory disturbance when compared with baseline (108569). Although the study also utilized mometasone 2 mg nasal spray and isotonic saline nasal irrigation as comparators, symptom improvement was observed in all three groups, and there was no statistical comparison of outcomes between groups.
Antipsychotic-induced hyperprolactinemia. Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in females with risperidone-induced hyperprolactinemia shows that taking a combination of licorice and peony (Peony-Glycyrrhiza Decoction; PGD) 45 grams daily for 4 weeks reduces prolactin levels to a similar extent as bromocriptine (59775). However, another study shows that taking the same product at the same dose for 16 weeks has no effect on prolactin levels in females with antipsychotic-induced hyperprolactinemia when compared with placebo. Although the prolactin-related adverse event questionnaire total score was moderately improved, there was no effect on clinically meaningful symptoms or menstrual resumption (97219). Both studies show no effect on psychotic symptoms (59775,97219). Preliminary clinical research in male patients with antipsychotic-induced hyperprolactinemia shows that taking an herbal extract containing licorice and peony (shakuyaku-kanzo-to) 2.5 grams three times daily reduces prolactin levels after 4 weeks, but does not have a significant effect on prolactin levels 4 weeks after treatment cessation (59907).
Bleeding. Topical licorice might reduce bleeding when used in combination with other ingredients; its effect when used alone is unclear. Details: Some preliminary clinical research shows that topically applying 4 mL of a specific product (Ankaferd Blood Stopper, Mefar Ilaç Sanayi A.S.) containing licorice, Alpinia, thyme, stinging nettle, and common grape vine reduces bleeding, but does not improve the surgical time for episiotomy repair, when compared with saline (31010). Other preliminary clinical research shows that ampules of this same product placed in empty alveolus for up to 20 minutes reduces bleeding in postsurgical dental patients with increased bleeding tendency (31002).
Cancer-related pain. It is unclear if oral licorice is beneficial for pain in patients with cancer. Details: Preliminary clinical research shows that taking a 1:1 combination of licorice root and peony root, along with a Taiwanese tonic vegetable soup comprised of lily bulb, lotus seed, and jujube fruit, reduces pain levels in terminal cancer patients when compared with patients consuming only the soup or the regular hospital diet (59770).
Chronic fatigue syndrome (CFS). Although there has been interest in using oral licorice for CFS, there is insufficient reliable information about the clinical effects of licorice for this condition.
Colic. Although there has been interest in using oral licorice for colic, there is insufficient reliable information about the clinical effects of licorice for this condition.
Coronavirus disease 2019 (COVID-19). Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients hospitalized in Egypt with moderate COVID-19 shows that administering oral licorice extract 300 mg (standardized to contain glycyrrhizin 60 mg) once daily and Boswellia serrata extract 300 mg twice daily for 14 days, along with following an institution-based COVID-19 treatment protocol, may modestly improve mortality and time to recovery when compared with patients receiving the standard protocol alone. The standard treatment protocol included acetaminophen, azithromycin, vitamin C, zinc, and enoxaparin (108579). It is unclear if any effect is due to licorice, Boswellia serrata, or the combination.
Dental caries. It is unclear if oral licorice is beneficial for the prevention of dental caries. Details: One clinical study in adults shows that swishing 15 mL of a solution containing licorice extract 1% once nightly before bed for 5 days may reduce the acid production of cavity-causing bacteria, which may modestly reduce cavity risk, when compared with using a saline solution (108567). The validity of this study is limited by the short duration of treatment and follow-up.
Dental plaque. It is unclear if licorice toothpaste or mouthwash is beneficial for reducing plaque. Details: Preliminary clinical research shows that using 0.25% or 0.50% glycyrrhizin-containing toothpaste twice daily does not reduce the amount of plaque, gingivitis, or bleeding in patients with proper dental hygienic measures when compared with the same toothpaste without glycyrrhizin (59812). Also, other preliminary clinical research shows that using glycyrrhizin-containing mouthwash for 3 days does not significantly reduce plaque levels (59855).
Depression. It is unclear if adding oral licorice to standard treatment is beneficial for improving depression. Details: A very small, nonblinded clinical study in hospitalized adults with major depressive disorder shows that adding licorice extract 1400 mg daily, standardized to glycyrrhizin 7% to 8%, to standard treatment for 2 weeks improves depression rating scores when compared with baseline, although these improvements were numerically similar to those seen with standard treatment alone. Patients in the treatment group also took oral magnesium citrate 300 mg daily to prevent magnesium depletion. The validity of this finding is limited due to the small size of the study, short duration of treatment, and unclear reporting (108575).
Diabetes. Although there has been interest in using oral licorice for diabetes, there is insufficient reliable information about the clinical effects of licorice for this condition.
Dry mouth. It is unclear if rinsing the mouth with licorice is beneficial for dry mouth in people on hemodialysis. Details: Preliminary clinical research in hemodialysis patients with dry mouth shows that rinsing with a licorice mouthwash containing 8.34 grams of licorice concentrate per 500 mL of water with every meal for 10 days does not affect salivary flow rate, but reduces subjective feelings of dry mouth by about 28%, when compared with a water-based mouthwash and control group (97220).
Dysmenorrhea. It is unclear if oral licorice is beneficial for reducing pain. Details: Preliminary clinical research shows that taking a syrup providing licorice extract 750 mg twice daily for the first 5 days of the menstrual cycle reduces pain as effectively as ibuprofen 400 mg every 8 hours in patients with moderate or severe dysmenorrhea (104558).
Dyspepsia. Oral licorice might improve symptoms of dyspepsia when used in combination with other ingredients; its effect when used alone is unclear. Details: Various combination products manufactured by Steigerwald Arzneimittelwerk GmbH have been evaluated for dyspepsia. Two specific combination products containing licorice root (Iberogast; STW-5-S) seem to improve symptoms of dyspepsia. The combinations include licorice plus milk thistle, peppermint leaf, German chamomile, caraway, celandine, angelica, and lemon balm either with (Iberogast) or without clown's mustard plant (STW-5-S) 1 mL three times daily for 4 weeks (19532). A meta-analysis of studies using the Iberogast product shows that taking 1 mL orally three times daily over a period of 4 weeks reduces severity of acid reflux, epigastric pain, cramping, nausea, and vomiting when compared with placebo (13089). Also, using a preparation containing clown's mustard plant, German chamomile, peppermint, caraway, licorice, and lemon balm (STW 5-II) 1 mL three times daily for up to 12 weeks improves dyspepsia symptoms in 40% more patients when compared with placebo (12724).
Familial Mediterranean fever. It is unclear if oral licorice is beneficial for familial Mediterranean fever. Details: Preliminary clinical research shows that taking a combination of licorice, andrographis, Siberian ginseng, and schisandra (ImmunoGuard, Inspired Nutritionals) four tablets three times daily for one month reduces the duration, frequency, and severity of attacks of familial Mediterranean fever in children when compared with placebo (12382). It is unclear if these effects are due to licorice, other ingredients, or the combination.
Helicobacter pylori. It is unclear if oral licorice is beneficial for Helicobacter pylori eradication. Details: Some preliminary clinical research shows that adding licorice (D-Reglis, Iran Darouk Pharmaceutical Co.) 380 mg twice daily to conventional clarithromycin-based triple therapy for 14 days improves eradication rate by an additional 21% when compared with conventional treatment alone. However, any additional benefit might be limited to patients with peptic ulcer disease (97221). Other preliminary clinical research shows that taking a combination of licorice extract 100 mg and Lactobacillus paracasei HP7 in 150 mL of fermented milk daily for 8 weeks does not increase eradication rates when compared with fermented milk alone, although it may improve gastrointestinal symptom scores, decrease the gastric load of Helicobacter pylori, and improve some measures of inflammation when compared to baseline (100984).
Hepatitis. Evidence for the use of intravenous licorice in the management of hepatitis B and C is mixed. Details: In some preliminary clinical research, a specific glycyrrhizin-containing intravenous preparation (Stronger Neominophagen C, Minophagen Pharmaceutical Co. Ltd.) appears to reduce mortality due to viral hepatitis by about 50% (3250). Other clinical research suggests that this same product reduces serum alanine aminotransferase (ALT) in hepatitis C patients but does not improve hepatitis C virus (HCV)-RNA levels (3247,59712,59721,59920). When used long-term, this preparation seems to reduce the risk of hepatocellular carcinoma in hepatitis C patients when compared to long-term use of other supplements, such as vitamin K (59905). This product has been used in various doses: 40 or 100 mL, containing 2 mg glycyrrhizin, 1 mg cysteine, and 20 mg of glycine per mL of solution, administered daily for 4-8 weeks, followed by 40 or 100 mL 2-7 times weekly for 2-16 weeks, has been used (3250,59905,59915); 40-120 mL diluted in 100 mL of 5% glucose solution and administered three times weekly for 4 weeks (59712,59721); 100 mL, which contained 200 mg glycyrrhizin, administered undiluted six times weekly for 4 weeks (59721); or 60 mL administered three times weekly for 16 weeks (59920). Other research shows that this preparation reduces ALT, aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) in patients with hepatitis B virus (59915). Oral licorice has not been evaluated for this purpose.
Hypercholesterolemia. It is unclear if oral licorice is beneficial for improving cholesterol. Details: Preliminary clinical research shows that taking licorice root extract 0.1 grams daily for one month reduces plasma total cholesterol levels by 5%, plasma low-density lipoprotein (LDL) cholesterol levels by 9%, and plasma triglyceride levels by 14% when compared with baseline in patients with moderate hypercholesterolemia (59725). The validity of these findings is limited by the lack of a comparator group.
Hyperkalemia. It is unclear if oral licorice is beneficial for reducing potassium levels. Details: Some clinical research in adults with diabetes and hypoaldosteronism suggests that taking glycyrrhizin 150 mg daily decreases potassium levels when compared with calcium polystyrene sulfonate (59897). Also, one very small clinical study in patients with anuria shows that taking glycyrrhetinic acid 1 gram daily for 2 weeks seems to decrease plasma potassium, but does not improve blood pressure, when compared with placebo (59723).
IgA vasculitis. Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small retrospective study in patients aged 5-36 years with newly diagnosed IgA vasculitis shows that taking compound glycyrrhizin (Eisai Pharmaceutical Co, Ltd) three times daily along with loratadine, calcium, vitamin C, rutin, and other unspecified conventional treatments is associated with an improvement in cutaneous purpura symptoms and time to symptom regression when compared with placebo. After 1 month, the rate of complete resolution and time to regression in the treatment group was 82% and 5 days, respectively, compared with 65% and 8 days, respectively, in the placebo group. Compound glycyrrhizin contained glycyrrhizin, glycine, and methionine and was dosed by age, with a dose of 25 mg daily in those 12 years or younger and 50 mg daily in those over 12 years (108580).
Irritable bowel syndrome (IBS). Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that a formulation containing licorice root, slippery elm bark, lactulose, and oat bran daily for 2 weeks improves stool consistency and increases bowel movement frequency by 20% in individuals with constipation-predominant IBS when compared to baseline. Symptoms of abdominal pain, bloating, straining, and global severity might also be reduced (35462). The validity of these findings is limited by the lack of a comparator group. Additionally, it is unclear if any benefits are due to licorice, other ingredients, or the combination.
Lichen planus. It is unclear if intravenous licorice is beneficial for lichen planus. Details: A very small clinical study shows that intravenous administration of 0.2% glycyrrhizin solution, 40 mL daily for 4 weeks, improves clinical symptoms of oral lichen planus in a greater percentage of patients with chronic hepatitis C when compared with dental cleaning (59903). There is no evidence suggesting that oral licorice is beneficial.
Liver cancer. Although there has been interest in using oral or intravenous licorice preparations for liver cancer, there is insufficient reliable information about the clinical effects of licorice for this condition.
Melasma. Topical licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a topical cream (Clariderm Clear, Stiefel Laboratories Inc.) containing 7% licorice, emblica, and belides twice daily for 60 days is as effective as a cream containing 2% hydroquinone for lightening the skin in patients with melasma (59824). It is unclear if this effect is due to licorice, other ingredients, or the combination.
Menopausal symptoms. It is unclear if oral licorice is beneficial for reducing hot flash frequency or severity. Details: In one preliminary clinical study, taking licorice root extract 330 mg orally three times daily for 8 weeks modestly reduces the frequency of hot flashes by about 1.3 per day and the severity of hot flashes by about 40% when compared with placebo (94659). However, another preliminary clinical study shows that taking a specific licorice root extract (D-Reglis, Iran Darouk Pharmaceutical Co.) 650 mg orally daily for 90 days does not reduce the number or severity of hot flashes when compared to baseline (25694).
Muscle cramps. It is unclear if oral licorice is beneficial for muscle cramps due to cirrhosis or hemodialysis. Details: Preliminary clinical research shows that taking a specific combination of licorice and peony (shakuyaku-kanzo-to) might reduce muscle cramps in patients with hepatic cirrhosis or in patients undergoing hemodialysis when compared to baseline (13550,13551,13552). This combination was taken as 6-7.5 grams daily in up to three divided doses for 2-4 weeks in two studies (13550,13552). In a third study, the combination was taken as 2.5 grams during hemodialysis with self-administration at the onset of muscle cramping (13551).
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral licorice is beneficial for NAFLD. Details: A small clinical trial in females with NAFLD shows that taking licorice extract (Shirin Darou Company, Shiraz, Iran) 500 mg twice daily for 12 weeks improves some measures of liver health and glycemic control when compared with placebo. Modest improvements occurred in levels of alanine aminotransferase, as well as in measures of insulin resistance and severity of liver steatosis based on ultrasonographic evaluation. There were no effects on body mass index (BMI), plasma lipids, fasting blood glucose, or other liver enzymes. All patients were also given weight loss and healthy lifestyle advice (110320). Preliminary clinical research shows that taking licorice root extract 2 grams daily for 2 months reduces liver function enzyme levels in patients with NAFLD when compared to pre-treatment (59841). It is unclear if this reduction is clinically significant.
Obesity. It is unclear if oral licorice is beneficial for weight loss. Details: Preliminary clinical research shows that taking a specific licorice flavonoid oil (Glavonoid) 300 mg daily for 8 weeks has no effect on weight or body fat when compared with placebo in obese patients (17727).
Oral mucositis. It is unclear if oral or topical licorice is beneficial for the prevention or treatment of chemotherapy- or radiation-induced oral mucositis. Details: In patients with head and neck cancer undergoing chemoradiation, preliminary clinical research shows that using oral and topical licorice powder twice daily in addition to conventional treatments for 6 weeks reduces the overall incidence of mucositis and also reduces the risk of developing severe oral mucositis to 15.5%, compared with 20% in those using topical honey and 43% in those using conventional treatments alone. Licorice treatment consisted of yastimadhu powder 5 grams mixed in honey for topical application in the mouth, as well as yastimadhu capsule 500 mg twice daily orally (104562). A small clinical trial in patients with head and neck cancer and oral mucositis currently undergoing radiation therapy shows that applying a mucoadhesive film containing licorice to the upper lip mucosal surface four times daily for 4 weeks, in conjunction with standard oral care, improves pain scores, mucositis grading, and ulcer size when compared with placebo film (108572). The validity of this finding is limited due to the short duration of treatment and exclusion of patients with severe mucositis.
Osteoarthritis. Although there has been interest in using oral licorice for osteoarthritis, there is insufficient reliable information about the clinical effects of licorice for this condition.
Osteoporosis. Although there has been interest in using oral licorice for osteoporosis, there is insufficient reliable information about the clinical effects of licorice for this condition.
Parkinson disease. It is unclear if oral licorice is beneficial for improving Parkinson disease symptoms. Details: A small clinical study in patients with Parkinson disease shows that taking licorice extract 136 mg (containing glycyrrhizin 12.14 mg, polyphenols 136 mcg, and flavonoids 2.6 mcg) in a 5 mL syrup twice daily for 6 months improves Parkinson symptoms, tremor, and overall daily activities when compared with placebo (102961).
Peptic ulcers. Evidence for the use of oral licorice for peptic ulcers is mixed. Details: There is some evidence that taking 6-12 tablets each containing deglycyrrhizinated licorice 380 mg, bismuth subnitrate 100 mg, aluminum hydroxide gel 100 mg, magnesium carbonate 200 mg, sodium bicarbonate 100 mg, and powdered alder buckthorn bark 30 mg (Caved-S, Cedona) in up to three divided doses daily for 4-16 weeks might accelerate the healing of peptic ulcers (11312,11313). Some clinical research also shows that this product is as effective as carbenoxolone sodium (Biogastrone) when taken at doses of two tablets three times daily after meals for 4 weeks (59871). In contrast, taking deglycyrrhizinated licorice (Ulcedal, Cedona, and others) 450-1000 mg three to five times daily for 4-8 weeks or glycyrrhizinic acid-reduced licorice 760 mg three times daily for 6 weeks does not seem to reduce the need for medication, pain, burning, or other discomfort in patients with peptic ulcers when compared with placebo (59864,59865,59873,59874).
Physical performance. It is unclear if oral licorice is beneficial for improving physical performance in older females. Details: A small clinical trial in healthy females 59 years and older shows that taking licorice flavonoid oil 300 mg orally daily for 16 weeks in addition to strength training does not improve walking speed or other measures of functional mobility when compared with strength training alone (102960).
Polycystic ovary syndrome (PCOS). Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking licorice root extract 2250 mg daily along with Ceylon cinnamon, levant berry, St. John's Wort, peony, and tribulus for 3 months with lifestyle modification improves symptoms of PCOS, including a reduction in oligomenorrhea/amenorrhea by 33% and the number of days between menstrual cycles by 43 days when compared with lifestyle modification alone. Although conception rate increased 4-fold in the intervention group, live birth rate was similar between groups (97216). The effect of licorice alone for the treatment of PCOS is unknown.
Prostate cancer. Although there has been interest in using oral licorice for prostate cancer, there is insufficient reliable information about the clinical effects of licorice for this condition.
Psoriasis. It is unclear if topical licorice is beneficial for improving psoriasis symptoms. Details: Preliminary clinical research shows that using a topical cream containing licorice extract and milk proteins twice daily for 4 weeks does not reduce the duration of corticosteroid cream therapy in patients with palmar and/or plantar psoriasis, but may improve skin peeling, the area of skin affected, and some subjective symptoms, when compared with corticosteroid cream alone (59823).
Systemic lupus erythematosus (SLE). Although there has been interest in using oral licorice for SLE, there is insufficient reliable information about the clinical effects of licorice for this condition.
Tuberculosis. Although there has been interest in using oral licorice for tuberculosis, there is insufficient reliable information about the clinical effects of licorice for this condition.
Urticaria. Oral licorice has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of clinical research in adults with chronic urticaria shows that taking compound glycyrrhizin, containing glycyrrhizin, N-acetyl cysteine, and glycine, as 50-75 mg three times daily along with desloratadine 5-8.8 mg daily for 4 weeks improves response rate, cure rate, and recurrence rate when compared with desloratadine alone (108571). However, most studies included in the meta-analysis were low quality, and all studies were conducted in China. Higher quality studies in other geographic locations are needed to confirm these findings.
Vitiligo. It is unclear if the licorice constituent compound glycyrrhizin is beneficial for vitiligo. Details: A meta-analysis of 14 clinical studies in patients aged 3-68 years old with vitiligo shows that taking licorice constituent compound glycyrrhizin 25-75 mg 3 times daily for 2-6 months with standard treatment improves effectiveness, cure rate, and immune-mediated inflammatory markers when compared with standard treatment alone (112232). More evidence is needed to rate licorice for these uses.

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.

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.

Safety view details

Below is general information about the safety of the known ingredients contained in the product Pitta Digest. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

CARDAMOM

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

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

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

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

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

LIKELY SAFE ...when consumed in amounts commonly found in foods. Cassia cinnamon has Generally Recognized As Safe (GRAS) status in the US for use as a spice or flavoring agent (4912) ...when used orally and appropriately, short-term. Cassia cinnamon 1-2 grams daily has been used safely for up to 3 months (17011,21914). Cassia cinnamon 3-6 grams daily has been used safely for up to 6 weeks (11347,14344). Cassia cinnamon extract corresponding to 3 grams daily of cassia cinnamon powder has also been used safely for up to 4 months (21916).

POSSIBLY SAFE ...when used topically, short-term. Cassia cinnamon oil 5% cream applied topically to the legs has been used safely in one clinical trial (59580).

POSSIBLY UNSAFE ...when used orally in high doses, long-term. Some cassia cinnamon products contain high levels of coumarin. Coumarin can cause hepatotoxicity in animal models (15299,21920). In humans, very high doses of coumarin from 50-7000 mg daily can result in hepatotoxicity that resolves when coumarin use is discontinued (15302). In most cases, ingestion of cassia cinnamon will not provide a high enough amount of coumarin to cause significant toxicity; however, in especially sensitive people, such as those with liver disease, prolonged ingestion of large amounts of cassia cinnamon might exacerbate the condition.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Cassia cinnamon 1 gram daily has been used safely in adolescents 13-18 years of age for up to 3 months (89648).

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods (4912). There is insufficient reliable information available about the safety of cassia cinnamon when used in medicinal amounts during pregnancy and breast-feeding. Stay on the safe side and stick to food amounts.

CELERY

LIKELY SAFE ...when celery stems are consumed as food. ...when celery oil or seeds are consumed in amounts commonly found in foods. Celery seed has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when celery seed is used orally and appropriately in medicinal amounts, short-term (12). Celery seed powder has been safely used at doses up to 1500 mg daily for up to 6 weeks and 750 mg daily for up to 12 weeks. Celery seed extract has been safely used at doses up to 1340 mg daily for up to 4 weeks (106486,110755,112409,112411). ...when celery seed extract is used topically and appropriately, short-term (40988,41049,41052).

PREGNANCY: LIKELY UNSAFE
when celery oil or seeds are used orally in larger amounts; celery might have uterine stimulant or abortifacient effects (4,19,19104).

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

CORIANDER

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

POSSIBLY SAFE ...when used orally and appropriately for medicinal purposes (12). ...when used topically and appropriately. Coriander oil 6% ointment has been used with apparent safety twice daily for up to 28 days (97874).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid amounts in excess of those found in foods.

CUMIN

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

POSSIBLY SAFE ...when the powder or essential oil is used orally and appropriately in medicinal amounts, short-term (12). Cumin essential oil has been used with apparent safety in doses up to 225 mg daily for up to 8 weeks or 100 mg daily for up to 6 months (100160,100162,104143). Cumin powder has been used with apparent safety in doses up to 3 grams daily for up to 6 months (100161,100162). There is insufficient reliable information available about the safety of cumin powder or essential oil when used orally, long-term.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in excess of food amounts.

FENNEL

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.

LIKELY SAFE ...when consumed in amounts commonly found in foods (6,2076).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Indian gooseberry fruit extract has been used safely in doses of up to 1000 mg daily for up to 6 months, 1500 mg daily for up to 8 weeks, or 2000 mg daily for up to 4 weeks (92515,99238,99240,99241,102855,102857,105352,105354,105356). Indian gooseberry leaf extract has been used with apparent safety at a dose of 750 mg daily for 10 days (99846). ...when used topically and appropriately. An emulsion containing Indian gooseberry extract 3% and other ingredients has been applied safely to the skin twice daily for up to 60 days (111571).

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

LICORICE

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

POSSIBLY SAFE ...when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes. Licorice flavonoid oil 300 mg daily for 16 weeks, and deglycyrrhizinated licorice products in doses of up to 4.5 grams daily for up to 16 weeks, have been used with apparent safety (6196,11312,11313,17727,100984,102960). ...when licorice products containing glycyrrhizin are used orally in low doses, short-term. Licorice extract 272 mg, containing glycyrrhizin 24.3 mg, has been used daily with apparent safety for 6 months (102961). A licorice extract 1000 mg, containing monoammonium glycyrrhizinate 240 mg, has been used daily with apparent safety for 12 weeks (110320). In addition, a syrup providing licorice extract 750 mg has been used twice daily with apparent safety for 5 days (104558). ...when applied topically. A gel containing 2% licorice root extract has been applied to the skin with apparent safety for up to 2 weeks. (59732). A mouth rinse containing 5% licorice extract has been used with apparent safety four times daily for up to one week (104564).

POSSIBLY UNSAFE ...when licorice products containing glycyrrhizin are used orally in large amounts for several weeks, or in smaller amounts for longer periods of time. The European Scientific Committee on Food recommends that a safe average daily intake of glycyrrhizin should not exceed 10 mg (108577). In otherwise healthy people, consuming glycyrrhizin daily for several weeks or longer can cause severe adverse effects including pseudohyperaldosteronism, hypertensive crisis, hypokalemia, cardiac arrhythmias, and cardiac arrest. Doses of 20 grams or more of licorice products, containing at least 400 mg glycyrrhizin, are more likely to cause these effects; however, smaller amounts have also caused hypokalemia and associated symptoms when taken for months to years (781,3252,15590,15592,15594,15596,15597,15599,15600,16058)(59731,59740,59752,59785,59786,59787,59792,59795,59805,59811)(59816,59818,59820,59822,59826,59828,59849,59850,59851,59867)(59882,59885,59888,59889,59895,59900,59906,97213,110305). In patients with hypertension, cardiovascular or kidney conditions, or a high salt intake, as little as 5 grams of licorice product or 100 mg glycyrrhizin daily can cause severe adverse effects (15589,15593,15598,15600,59726).

PREGNANCY: UNSAFE
when used orally. Licorice has abortifacient, estrogenic, and steroid effects. It can also cause uterine stimulation. Heavy consumption of licorice, equivalent to 500 mg of glycyrrhizin per week (about 250 grams of licorice per week), during pregnancy seems to increase the risk of delivery before gestational age of 38 weeks (7619,10618). Furthermore, high intake of glycyrrhizin, at least 500 mg per week, during pregnancy is associated with increased salivary cortisol levels in the child by the age of 8 years. This suggests that high intake of licorice during pregnancy may increase hypothalamic-pituitary-adrenocortical axis activity in the child (26434); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

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.

Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product Pitta Digest. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

CARDAMOM

None known.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, cassia cinnamon may have additive effects with antidiabetes drugs.

Details

Cassia cinnamon may lower blood glucose levels, and have additive effects in patients treated with antidiabetic agents (11347,17011,21914,21918,89649). Dose adjustments to diabetes medications might be necessary.

HEPATOTOXIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, large doses of cassia cinnamon might cause additive effects when used with hepatotoxic drugs.

Details

There is some concern that ingesting large amounts of cassia cinnamon for an extended duration might cause hepatotoxicity in some people. Cassia cinnamon contains coumarin, which can cause hepatotoxicity in animal models (15299,21920). In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin use is discontinued (15302,97249). Lower amounts might also cause liver problems in sensitive people, such as those with liver disease or those taking potentially hepatotoxic agents.

CELERY

ACETAMINOPHEN (Tylenol, others)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, celery juice might increase the effects and side effects of acetaminophen.

Details

Animal research suggests that concomitant use of celery juice plus acetaminophen prolongs the effects of acetaminophen. This effect has been attributed to a decrease in hepatic cytochrome P450 activity (25362). However, other animal research shows that pretreatment with celery root extract protects against acetaminophen-induced acute liver failure (106487). These effects have not been reported in humans.

AMINOPYRINE

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, celery juice might increase the effects and side effects of aminopyrine.

Details

Animal research suggests that concomitant use of celery juice plus aminopyrine prolongs the effects of aminopyrine. This effect has been attributed to a decrease in hepatic cytochrome P450 activity (25362). This effect has not been reported in humans.

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, celery root might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.

Details

Celery root contains the constituents falcarinol and falcarindiol. Laboratory research suggests that these constituents can inhibit platelet aggregation (6048,40991). This effect has not been reported in humans.

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Theoretically, celery seed extract might have additive effects with antihypertensive drugs.

Details

Clinical research suggests that taking celery seed extract may reduce daytime systolic blood pressure by about 12 mmHg compared to less than 1 mmHg with placebo (110755).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, celery might increase levels of drugs metabolized by CYP1A2.

Details

In vitro and animal research suggests that constituents of celery can inhibit CYP1A2 (68176). This effect has not been reported in humans.

LEVOTHYROXINE (Synthroid, others)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, celery seed might decrease the effects of levothyroxine.

Details

Several cases of hypothyroidism with low T4 levels have been reported in people who were previously stabilized on levothyroxine and then started taking celery seed tablets. They presented with symptoms such as lethargy, bloating, and dry skin, and recovered when celery seed was stopped (10646). However, celery stem and leaf has been associated with case reports of hyperthyroidism in patients with no pre-existing thyroid disorders (102912,102914).

LITHIUM

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = D

Theoretically, celery might reduce excretion and increase levels of lithium due to potential diuretic effects.

Details

Celery is thought to have diuretic properties (4,6). However, this effect has not been confirmed in humans.

PHOTOSENSITIZING DRUGS

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, celery might increase the risk of photosensitivity reactions when taken with photosensitizing drugs.

Details

Laboratory research shows that celery contains photosensitizing agents such as phenols and psoralens (6178,40894,40917,41073,41121).

VENLAFAXINE (Effexor)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, celery root extract might increase blood levels of venlafaxine.

Details

There is one case report of a patient who experienced medication-induced bipolar disorder after beginning to take celery root extract 1000 mg daily along with venlafaxine 75 mg and St. John's wort 600 mg daily. Symptoms included confusion, speech abnormalities, manic affect, and visual hallucinations. The plasma level of venlafaxine was 476.8 ng/mL (normal range 195-400 ng/mL). It is theorized that celery root increased venlafaxine levels by inhibiting cytochrome P450 2D6 (92854).

CORIANDER

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, coriander might increase the risk of hypoglycemia when taken with antidiabetes drugs.

Details

Evidence from animal research suggests that coriander fruit and coriander extract can reduce blood glucose levels (14907,46153,46216). Monitor blood glucose levels closely. Dose adjustments might be necessary.

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, coriander might increase the risk of hypotension when taken with antihypertensive drugs.

Details

Evidence from animal research suggests that coriander fruit can lower blood pressure (46221).

CNS DEPRESSANTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, coriander might cause additive sedative effects when taken with CNS depressants.

Details

Evidence from animal research suggests that coriander fruit extract has sedative effects (46184).

PHOTOSENSITIZING DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, coriander might increase the risk of photosensitivity when taken with photosensitizing drugs.

Details

Evidence from in vitro research suggests that coriandrin, a constituent of coriander, has photosensitizing effects (46228).

CUMIN

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, cumin might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.

Details

In vitro evidence suggests that cumin can inhibit platelet aggregation (46897). Theoretically, cumin might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = D

Theoretically, cumin might increase the risk of hypoglycemia when taken with antidiabetes drugs.

Details

Animal research suggests that cumin can lower blood sugar in diabetic animals (19,46857,46895). However, research in humans with and without diabetes has found conflicting results (106516,106517).

RIFAMPIN (Rifadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, cumin might increase the effects and adverse effects of rifampin.

Details

Animal research suggests that an aqueous extract of cumin containing a specific flavonoid glycoside can increase the bioavailability and plasma levels of rifampin (46876).

FENNEL

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.

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Theoretically, Indian gooseberry may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs; however, research is conflicting.

Details

Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking Indian gooseberry 500 mg along with clopidogrel 75 mg or ecosprin 75 mg, as a single dose or for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg or ecosprin 75 mg alone (92514). Until more is known, use caution when taking Indian gooseberry in combination with anticoagulant/antiplatelet drugs.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Taking Indian gooseberry with antidiabetes drugs might increase the risk of hypoglycemia.

Details

Clinical research shows that taking Indian gooseberry fruit or fruit extract alone or in conjunction with antidiabetes medications can lower blood glucose levels (31025,105355,105356,111569). Dose adjustments to diabetes medications might be necessary.

ASPIRIN

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Theoretically, Indian gooseberry may increase the risk of bleeding if used with aspirin; however, research is conflicting.

Details

Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with ecosprin 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus ecosprin 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with ecosprin 75 mg alone (92514).

CLOPIDOGREL (Plavix)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Theoretically, Indian gooseberry may increase the risk of bleeding if used with clopidogrel; however, research is conflicting.

Details

Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with clopidogrel 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus clopidogrel 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg alone (92514).

LICORICE

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, licorice might reduce the effects of antihypertensive drugs.

Details

In human research, licorice increases blood pressure in a dose-dependent manner (1372,7620,59877).

CISPLATIN (Platinol-AQ)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, licorice might reduce the effects of cisplatin.

Details

In animal research, licorice diminished the therapeutic efficacy of cisplatin (59763).

CORTICOSTEROIDS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, concomitant use of licorice and corticosteroids might increase the side effects of corticosteroids.

Details

Case reports suggest that concomitant use of licorice and oral corticosteroids, such as hydrocortisone, can potentiate the duration of activity and increase blood levels of corticosteroids (3252,12672,20040,20042,48429,59756). Additionally, in one case report, a patient with neurogenic orthostatic hypertension stabilized on fludrocortisone 0.1 mg twice daily developed pseudohyperaldosteronism after recent consumption of large amounts of black licorice (108568).

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, licorice might increase levels of drugs metabolized by CYP2B6.

Details

In vitro research shows that licorice extract and glabridin, a licorice constituent, inhibit CYP2B6 isoenzymes (10300,94822). Licorice extract from the species G. uralensis seems to inhibit CYP2B6 isoenzymes to a greater degree than G. glabra extract in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2B6; however, these interactions have not yet 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, licorice might increase levels of drugs metabolized by CYP2C19.

Details

In vitro, licorice extracts from the species G. glabra and G. uralensis inhibit CYP2C19 isoenzymes in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C19; however, this interaction has not yet 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, licorice might increase levels of drugs metabolized by CYP2C8.

Details

In vitro, licorice extract from the species G. glabra and G. uralensis inhibits CYP2C8 isoenzymes (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C8; however, this interaction has not yet 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, licorice might increase or decrease levels of drugs metabolized by CYP2C9.

Details

There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes (10300,94822). However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity (14441). Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.

Details

Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity (59808). Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity (14441). However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species (10300,94822). Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.

DIGOXIN (Lanoxin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, concomitant use of licorice with digoxin might increase the risk of cardiac toxicity.

Details

Overuse or misuse of licorice with cardiac glycoside therapy might increase the risk of cardiac toxicity due to potassium loss (10393).

DIURETIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, concomitant use of licorice with diuretic drugs might increase the risk of hypokalemia.

Details

Overuse of licorice might compound diuretic-induced potassium loss (10393,20045,20046,59812). In one case report, a 72-year-old male with a past medical history of hypertension, type 2 diabetes, hyperlipidemia, arrhythmia, stroke, and hepatic dysfunction was hospitalized with severe hypokalemia and uncontrolled hypertension due to pseudohyperaldosteronism. This was thought to be provoked by concomitant daily consumption of a product containing 225 mg of glycyrrhizin, a constituent of licorice, and hydrochlorothiazide 12.5 mg for 1 month (108577).

ESTROGENS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, licorice might increase or decrease the effects of estrogen therapy.

Details

Theoretically, licorice might interfere with estrogen therapy due to estrogenic and anti-estrogenic effects (7860,16058).

LOOP DIURETICS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.

Details

Theoretically, loop diuretics might enhance the mineralocorticoid effects of licorice by inhibiting the enzyme that converts cortisol to cortisone; however, bumetanide (Bumex) does not appear to have this effect (3255).

METHOTREXATE (Trexall, others)

Interaction Rating = Minor Be watchful with this combination.

Severity = Moderate • Occurrence = Unlikely • Level of Evidence = D

Theoretically, licorice might increase levels of methotrexate.

Details

Animal research suggests that intravenous administration of glycyrrhizin, a licorice constituent, and high-dose methotrexate may delay methotrexate excretion and increase systemic exposure, leading to transient elevations in liver enzymes and total bilirubin (108570). This interaction has not yet been reported in humans.

MIDAZOLAM (Versed)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, licorice might decrease levels of midazolam.

Details

In humans, the licorice constituent glycyrrhizin appears to moderately induce the metabolism of midazolam (59808). This is likely due to induction of cytochrome P450 3A4 by licorice. Until more is known, licorice should be used cautiously in people taking midazolam.

P-GLYCOPROTEIN SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.

Details

In vitro research shows that licorice can increase P-glycoprotein activity (104561).

PACLITAXEL (Abraxane, Onxol)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, licorice might decrease plasma levels and clinical effects of paclitaxel.

Details

Multiple doses of licorice taken concomitantly with paclitaxel might reduce the effectiveness of paclitaxel. Animal research shows that licorice 3 grams/kg given orally for 14 days before intravenous administration of paclitaxel decreases the exposure to paclitaxel and increases its clearance. Theoretically, this occurs because licorice induces cytochrome P450 3A4 enzymes, which metabolize paclitaxel. Notably, a single dose of licorice did not affect exposure or clearance of paclitaxel (102959).

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, licorice might decrease plasma levels and clinical effects of warfarin.

Details

Licorice seems to increase metabolism and decrease levels of warfarin in animal models. This is likely due to induction of cytochrome P450 2C9 (CYP2C9) metabolism by licorice (14441). Advise patients taking warfarin to avoid taking licorice.

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).

Report an Adverse Reaction to Pitta Digest

Adverse Effects view details

Below is general information about the adverse effects of the known ingredients contained in the product Pitta Digest. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

CARDAMOM

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

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

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

General ...Orally, cassia cinnamon appears to be well-tolerated. Significant side effects have not been reported in most patients.
Most Common Adverse Effects:
Topically: Burning mouth, stomatitis.

Dermatologic ...In one clinical trial, a rash was reported in one patient taking cassia cinnamon 1 gram daily for 90 days (17011).
In one case, a 58-year-old female with a documented allergy to topically applied cinnamic alcohol presented with eyelid dermatitis, which was found to be a manifestation of systemic contact dermatitis to cinnamon in the diet. Symptoms improved in two days and completely cleared five days after discontinuing the addition of cinnamon to food products (95599). In other case reports, two adults presented with allergic contact cheilitis following the ingestion of chai tea with cinnamon and yogurt with cinnamon. Cinnamon components were confirmed as the causative allergic agents with patch tests, and both cases of allergic contact cheilitis completely resolved upon cessation of the cinnamon-containing products (113516,113515).
Topically, allergic skin reactions and stomatitis from toothpaste flavored with cassia cinnamon have been reported (11915,11920). Intraoral allergic reactions with symptoms of tenderness and burning sensations of the oral mucosa have also been reported in patients using breath fresheners, toothpaste, mouthwash, candy, or chewing gum containing cinnamon, cinnamic aldehyde or cinnamic alcohol as flavoring agents. Glossodynia, or burning mouth syndrome, has also been reported in a 62-year-old female who ate apples dipped in cinnamon nightly (95598), and allergic contact dermatitis has been reported in a teenage female using a homemade cinnamon sugar face scrub (95596).

Endocrine ...In one clinical trial, a hypoglycemic seizure was reported in one patient taking cassia cinnamon 1 gram daily for 3 months. The event occurred one day after enrolling in the study (89648). It is unclear if cassia cinnamon caused this event.

Hepatic ...There is some concern about the safety of ingesting large amounts of cassia cinnamon for extended durations due to its coumarin content. Coumarin can cause hepatotoxicity in animal models (15299). In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin is discontinued (15302). In clinical trials, taking cassia cinnamon 360 mg to 12 grams daily for 3 months did not significantly increase levels of aspartate transaminase (AST) or alanine transaminase (ALT) (21918,96280,108259). However, in one case report, acute hepatitis with elevated AST and ALT occurred in a 73-year-old female who started taking a cinnamon supplement (dose unknown) one week prior to admission. The cinnamon supplement was added on to high-dose rosuvastatin, which may have led to additive adverse hepatic effects. After discontinuing both products, liver function returned to normal, and the patient was able to restart rosuvastati without further complications (97249). In most cases, ingestion of cassia cinnamon won't provide a high enough amount of coumarin to cause significant toxicity; however, in especially sensitive people, such as those with liver disease or taking potentially hepatotoxic agents, prolonged ingestion of large amounts of cassia cinnamon might exacerbate the condition.

Immunologic ...An unspecified allergic reaction was reported in one patient taking cassia cinnamon 1 gram daily for 3 months (89648).

CELERY

General ...Orally, celery seems to be well tolerated.
Most Common Adverse Effects:
Orally: Photosensitivity. Oral allergy syndrome in sensitive individuals.
Topically: Photosensitivity. Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.

Dermatologic ...Due to its psoralen content, contact with or ingestion of celery and exposure to ultraviolet radiation may cause photodermatitis (4,34347,40968,40969,40986,41085,41087,41143,41146,41151). Acute symptoms include skin eruption with edema and erythema; the main chronic symptom is hyperpigmentation at the eruption site (41093).
Celery can also cause contact or atopic dermatitis (19,41118,41124) and urticaria pigmentosa (40908).

Endocrine ...Celery has been associated with hyperthyroidism in otherwise healthy adults. In one case report a 36-year-old female presented with weight loss, blurred vision, nausea, palpitations, sweating, exophthalmos, elevated serum T4 levels, and low thyroid stimulating hormone (TSH) levels after taking 8 grams of a powdered celery extract for 78 days (102912). In another case report, a 48-year-old male presented with weight loss, exophthalmos, sweating, elevated serum T4 levels, and low TSH levels after taking 4 grams of dried celery leaves for 45 days (102914). In both of these cases, symptoms resolved and thyroid function tests normalized after discontinuing celery and completing a course of methimazole.
In contrast, several cases of hypothyroidism with low T4 levels have been reported in people who were previously stabilized on levothyroxine and then started taking celery seed tablets. They presented with symptoms such as lethargy, bloating, and dry skin, and recovered when celery seed was stopped (10646).

Gastrointestinal ...Symptoms of celery allergy have included oral allergy syndrome, characterized by itching and burning in the mouth and throat (41159,40977), and laryngeal edema (40953).

Immunologic ...Raw celery, cooked celery, and celery juice can all cause allergic reactions (40908,40926,41118,41131,92852,92855). Symptoms of celery allergy include laryngeal edema, skin reactions, an urticaria-edema-anaphylactic shock syndrome, celery-dependent exercise-induced anaphylaxis, and anaphylactic shock (40953,41100,41102,41107,41115,41124,41129,41135,41137,92852)(92855). Additionally, in clinical research, itchy throat has been reported in individuals taking celery seed powder (112410).
There is a case report of anaphylactic shock involving hypotension, tachycardia, and tachypnea in a patient who had ingested raw celery 15 minutes prior to symptom onset. The patient was treated with epinephrine, dexamethasone, and antazoline (92855). Another case report describes a patient with positive skin prick tests to celery, pollens including birch, chrysanthemum, mugwort, and ragweed, and to dust mites. When celery was consumed 30 minutes prior to exercise, the patient had an anaphylactic reaction that required treatment with intravenous pheniramine and corticosteroid, as well as nebulized albuterol (92852). Another patient with a history of anaphylactic reactions to undeclared celery in restaurant meals was able to undergo desensitization with gradually increasing oral doses of celery juice over several months, and then chronic daily ingestion of the juice to maintain hyposensitization (40908).

CORIANDER

General ...Orally and topically, coriander seems to be well tolerated.
Most Common Adverse Effects:
Topically: Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.

Dermatologic ...Topically, coriander can cause pruritus and a burning sensation (97874).

Immunologic ...A case of anaphylactic reaction characterized by generalized urticaria, conjunctivitis, oropharyngeal angioedema, and bronchospasms has been reported in a 25-year-old spice worker who consumed food containing coriander fruit. The digestive spice allergy was attributed to sensitization to coriander caused by occupational exposure to coriander fruit, powder, and dust (46192). Also, cases of rhinitis and symptoms of asthma have been reported for patients exposed to dust from coriander spice, particularly people working with spices in the food industry (46226,46245). Like other members of the Apiaceae/Umbelliferae (carrot family), coriander can cause contact dermatitis (19). A case of occupational protein contact dermatitis has been reported for an individual exposed to coriander fruit (46168).

CUMIN

General ...Orally, cumin powder and essential oil seem to be well tolerated, short-term.
Most Common Adverse Effects:
Orally: Gastrointestinal upset.
Topically: Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.

Dermatologic ...Topically, undiluted cumin oil has been reported to cause phototoxic effects (6).

Gastrointestinal ...Orally, gastrointestinal upset has been reported in some patients taking cumin essential oil (104143).

Immunologic ...Orally, cumin may cause allergic reactions, including anaphylaxis, in sensitive individuals. One case report of anaphylaxis associated with cumin consumption has been reported (46905).
Topically, cumin may cause allergic contact dermatitis in sensitive individuals (31341,46902,46905).

FENNEL

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).

General ...Orally, Indian gooseberry seems to be well tolerated.

Dermatologic ...Orally, itching has been reported by one individual in a clinical trial (105354).

Gastrointestinal ...Orally, epigastric discomfort or dyspepsia have been reported by up to four individuals in clinical trials (105354,105356).

Hepatic ...In clinical research, increased serum glutamic pyruvic transaminase (SGPT) levels, with otherwise normal liver function, occurred in patients taking Ayurvedic formulations containing ginger, Tinospora cordifolia, and Indian gooseberry, with or without Boswellia serrata. The SGPT levels normalized after discontinuing the treatments (89557). It is unclear if these hepatic effects were due to Indian gooseberry or other ingredients contained in the formulations.

Musculoskeletal ...Orally, musculoskeletal pain has been reported by three individuals in a clinical trial (105354).

Neurologic/CNS ...Orally, fatigue has been reported by one individual in a clinical trial (105354).

Pulmonary/Respiratory ...Orally, breathlessness has been reported by one individual in a clinical trial (105354).

LICORICE

General ...Orally, licorice is generally well tolerated when used in amounts commonly found in foods. It seems to be well tolerated when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes or when used topically, short-term.
Most Common Adverse Effects:
Orally: Headache, nausea, and vomiting.
Topically: Contact dermatitis.
Intravenously: Diarrhea, itching, nausea, and rash.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about acute renal failure, cardiac arrest, cardiac arrhythmias, hypertension, hypokalemia, muscle weakness, paralysis, pseudohyperaldosteronism, and seizure associated with long-term use or large amounts of licorice containing glycyrrhizin.

Cardiovascular ...Orally, excessive licorice ingestion can lead to pseudohyperaldosteronism, which can precipitate cardiovascular complications such as hypertension and hypertensive crisis, ventricular fibrillation or tachycardia, sinus pause, and cardiac arrest. These effects are due to the licorice constituent glycyrrhizin and usually occur when 20-30 grams or more of licorice product is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,97213) (104563,108574,108576,110305,112234). In one case report, an 89-year-old female taking an herbal medicine containing licorice experienced a fatal arrhythmia secondary to licorice-induced hypokalemia. The patient presented to the hospital with recurrent syncope, weakness, and fatigue for 5 days after taking an herbal medicine containing licorice for 2 months. Upon admission to the hospital, the patient developed seizures, QT prolongation, and ventricular arrhythmia requiring multiple defibrillations. Laboratory tests confirmed hypokalemia and pseudohyperaldosteronism (112234).
However, people with cardiovascular or kidney conditions may be more sensitive, so these adverse events may occur with doses as low as 5 grams of licorice product or glycyrrhizin 100 mg daily (15589,15593,15598,15600,59726). A case report in a 54-year-old male suggests that malnutrition might increase the risk of severe adverse effects with excessive licorice consumption. This patient presented to the emergency room with cardiac arrest and ventricular fibrillation after excessive daily consumption of licorice for about 3 weeks. This caused pseudohyperaldosteronism and then hypokalemia, leading to cardiovascular manifestations. In spite of resuscitative treatment, the patient progressed to kidney failure, refused dialysis, and died shortly thereafter (103791).

Dermatologic ...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912). There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578). Burning sensation, itching, redness, and scaling were reported rarely in patients applying a combination of licorice, calendula, and snail secretion filtrate to the face. The specific role of licorice is unclear (110322).
In rare cases, the glycyrrhizin constituent of licorice has caused rash and itching when administered intravenously (59712).

Endocrine ...Orally, excessive licorice ingestion can cause a syndrome of apparent mineralocorticoid excess, or pseudohyperaldosteronism, with sodium and water retention, increased urinary potassium loss, hypokalemia, and metabolic alkalosis due to its glycyrrhizin content (781,10619,15591,15592,15593,15594,15595,15596,15597,15598)(15600,16057,16835,25659,25660,25673,25719,26439,59818,59822)(59832,59864,91722,104563,108568,108574,110305,112234). These metabolic abnormalities can lead to hypertension, edema, EKG changes, fatigue, syncope, arrhythmias, cardiac arrest, headache, lethargy, muscle weakness, dropped head syndrome (DHS), rhabdomyolysis, myoglobinuria, paralysis, encephalopathy, respiratory impairment, hyperparathyroidism, and acute kidney failure (10393,10619,15589,15590,15593,15594,15596,15597,15599)(15600,16057,16835,25660,25673,25719,26439,31562,59709,59716)(59720,59740,59787,59820,59826,59882,59889,59900,91722,97214,100522) (104563,108576,108577). These effects are most likely to occur when 20-30 grams of licorice products containing glycyrrhizin 400 mg or more is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,108574). However, some people may be more sensitive, especially those with hypertension, diabetes, heart problems, or kidney problems (15589,15593,15598,15600,59726,108576,108577) and even low or moderate consumption of licorice may cause hypertensive crisis or hypertension in normotensive individuals (1372,97213). The use of certain medications with licorice may also increase the risk of these adverse effects (108568,108577). One case report determined that the use of large doses of licorice in an elderly female stabilized on fludrocortisone precipitated hypokalemia and hypertension, requiring inpatient treatment (108568). Another case report describes severe hypokalemia necessitating intensive care treatment due to co-ingestion of an oral glycyrrhizin-specific product and hydrochlorothiazide for 1 month (108577). Glycyrrhetinic acid has a long half-life, a large volume of distribution, and extensive enterohepatic recirculation. Therefore, it may take 1-2 weeks before hypokalemia resolves (781,15595,15596,15597,15600). Normalization of the renin-aldosterone axis and blood pressure can take up to several months (781,15595,108568). Treatment typically includes the discontinuation of licorice, oral and intravenous potassium supplementation, and short-term use of aldosterone antagonists, such as spironolactone (108574,108577).
Chewing tobacco flavored with licorice has also been associated with toxicity. Chewing licorice-flavored tobacco, drinking licorice tea, or ingesting large amounts of black licorice flavored jelly beans or lozenges has been associated with hypertension and suppressed renin and aldosterone levels (12671,12837,97214,97215,97217,108574). One case report suggests that taking a combination product containing about 100 mg of licorice and other ingredients (Jintan, Morishita Jintan Co.) for many decades may be associated with hypoaldosteronism, even up to 5 months after discontinuation of the product (100522). In another case report, licorice ingestion led to hyperprolactinemia in a female (59901). Licorice-associated hypercalcemia has also been noted in a case report (59766).

Gastrointestinal ...Nausea and vomiting have been reported rarely following oral use of deglycyrrhizinated licorice (25694,59871). Intravenously, the glycyrrhizin constituent of licorice has rarely caused gastric discomfort, diarrhea, or nausea (59712,59915).

Immunologic ...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912). There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578).

Musculoskeletal ...In a case report, excessive glycyrrhizin-containing licorice consumption led to water retention and was thought to trigger neuropathy and carpal tunnel syndrome (59791).

Neurologic/CNS ...Orally, licorice containing larger amounts of glycyrrhizin may cause headaches. A healthy woman taking glycyrrhizin 380 mg daily for 2 weeks experienced a headache (59892). Intravenously, the glycyrrhizin constituent of licorice has rarely caused headaches or fatigue (59721). In a case report, licorice candy ingestion was associated with posterior reversible encephalopathy syndrome accompanied by a tonic-clonic seizure (97218).

Ocular/Otic ...Orally, consuming glycyrrhizin-containing licorice 114-909 grams has been associated with transient visual loss (59714).

Pulmonary/Respiratory ...Orally, large amounts of licorice might lead to pulmonary edema. In one case report, a 64-year old male consumed 1020 grams of black licorice (Hershey Twizzlers) containing glycyrrhizin 3.6 grams over 3 days, which resulted in pulmonary edema secondary to pseudohyperaldosteronism (31561). Intravenously, the glycyrrhizin constituent of licorice has caused cold or flu-like symptoms, although these events are not common (59712,59721).

Report an Adverse Reaction to Pitta Digest

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).