Liver Reset by Organifi

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Constipation. Although there has been interest in using oral dandelion for constipation, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Dyspepsia. Although there has been interest in using oral dandelion for dyspepsia, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Flatulence. Although there has been interest in using oral dandelion for flatulence, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Heart failure. Although there has been interest in using oral dandelion for its diuretic effects in patients with heart failure, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Joint pain. Although there has been interest in using oral or topical dandelion for joint pain, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Tonsillitis. It is unclear if oral dandelion is beneficial in patients with tonsillitis. Details: One small clinical study in patients with acute purulent tonsillitis shows that eating soup containing dandelion (pugongying soup) daily for 3 days along with benzylpenicillin sodium 640,000 units daily improves recovery when compared with placebo plus benzylpenicillin sodium. Recovery rates were 36% with the dandelion-containing soup compared to 10% with placebo (18292).
• Urinary tract infections (UTIs). Oral dandelion has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in females with recurrent UTIs shows that taking a specific combination of dandelion root and uva ursi leaf extracts three times daily for 1 month reduces the risk of UTI recurrence when compared with placebo at 12-month's follow-up. For every 5 patients treated with this combination over placebo, one additional UTI was prevented (1932). In this combination, uva ursi is used for its antibacterial properties and dandelion is used to increase urination. However, this combination is not recommended for extended use because uva ursi may be unsafe when used long-term. Another small clinical study in premenopausal females with acute, uncomplicated lower UTIs shows that taking a combination product containing dandelion extract 50 mg, D-mannose, prebiotics, arabinogalactan, and astragalus root extract twice daily for five days, along with phenazopyridine and alkylating agents as conventional therapy, improves UTI symptoms and bacteriuria when compared with placebo plus conventional therapy (111757). It is unclear if these effects are due to dandelion, other ingredients, or the combination. More evidence is needed to rate dandelion for these uses.

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POSSIBLY EFFECTIVE

• 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).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• 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.

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POSSIBLY EFFECTIVE

• Diabetes. Oral milk thistle extracts of silymarin seem to improve glycemic control in diabetic patients. Details: A meta-analysis of 7 small heterogeneous clinical trials in patients with type 2 diabetes shows that taking milk thistle containing silymarin 210-600 mg alone or with other ingredients daily for up to 6 months reduces fasting blood glucose and glycated hemoglobin when compared with control. Sub-group analyses suggest that studies conducted for less than 3 months seem to have a greater glycemic benefit than those lasting 3 months or longer. Furthermore, there was a greater glycemic benefit when milk thistle was used in combination with other natural ingredients (105054). Most studies in the analysis used silymarin in divided doses of 420-600 mg daily, while only one study used 200 mg daily (15102,63190,97626,105054). Most of these studies were conducted in the Middle East, so it is unclear whether these results are generalizable to other geographic locations. Most studies of combination products have been conducted in Italy and involve a specific product (Berberol, PharmExtracta) containing milk thistle standardized to silymarin 105-210 mg with tree turmeric standardized to berberine 500-1000 mg (96141,105054). In addition to improving glycemic indices in patients with type 2 diabetes (105054), this product has shown glycemic benefit in patients with concomitant obesity and metabolic syndrome (97624) and in patients with type 1 diabetes (96142).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if oral or topical milk thistle is beneficial in patients with acne when used alone or in combination with other treatments. Details: A small clinical trial in patients with acne vulgaris shows that taking a milk thistle extract standardized to silymarin 140 mg daily for 2 months does not improve acne severity based on the Global Acne Grading system scale when compared with doxycycline 100 mg daily, and silymarin is less effective than doxycycline when evaluated using the Acne Severity Index (ASI) scale. In addition, using silymarin in combination with doxycycline does not appear to be more effective than doxycycline alone (101160). There is also interest in using milk thistle topically for acne. A clinical study in adults with acne vulgaris shows that applying a specific topical product (Silymarin CF, Skinceuticals) containing silymarin 0.5%, vitamin C 15%, salicylic acid 0.5% and ferulic acid 0.5%, twice daily for 3 months moderately improves acne scores when compared to baseline (110488). Additionally, a small quasi-experimental study in adults with mild to moderate acne suggests that applying silymarin 1.4% cream twice daily for 3 months improves global acne scores and appearance of acne when compared to baseline, but not when compared with biweekly salicylic acid chemical peels (113143). However, the interpretation of these results is limited by the use of subjective outcomes. Similarly, observational research in patients aged 12-25 years with mild-to-moderate acne has found that applying a specific cream (Cleanance Comedomed, Pierre Fabre Dermo-Cosmetique) containing milk thistle fruit extract 25% twice daily for 8-12 weeks as initial or add-on therapy moderately improves acne scores when compared to baseline (111175). The interpretation of these results is limited by the lack of a comparator group. Further, most patients were also prescribed other skincare products or treatments.
• Alcohol-related liver disease. It is unclear if oral milk thistle is beneficial in patients with alcohol-related liver disease, as evidence is conflicting. Details: Some preliminary research shows that taking a milk thistle extract containing 70% to 80% silymarin (Legalon, Madaus GmbH) 420 mg orally daily for one month to 4 years improves some liver function tests (2613,2618,17228,63260,63339). Some studies also report improvements in liver histology and survival (2616,17228,63278). However, in other studies, taking a similar dose of the same product for 3 months to 2 years is not associated with any benefit over placebo (7321,7322,7355,63158). A meta-analysis of clinical research also shows that milk thistle extract does not reduce mortality or complications related to liver disease in patients with alcohol-related liver disease (63192). Reasons for the conflicting findings are unclear but might relate to the low methodological quality of many of these studies.
• Allergic rhinitis (hay fever). It is unclear if oral milk thistle is beneficial in patients with allergic rhinitis. Details: One preliminary clinical trial shows that taking a milk thistle extract of silymarin 140 mg orally three times a day plus cetirizine (Zyrtec) 10 mg daily for one month decreases the severity of allergic rhinitis symptoms when compared with placebo plus cetirizine (18105).
• Alzheimer disease. Oral milk thistle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a supplement containing a milk thistle extract of silymarin 150 mg in combination with ferulic acid, gamma-oryzanol, and apigenin orally twice daily for 3 months to 2 years may stabilize mental functioning in patients with Alzheimer disease when compared to baseline (63223). It is unclear if this effect is due to milk thistle, other ingredients, or the combination.
• Amanita mushroom poisoning. While an intravenous milk thistle constituent, silibinin, has been studied for treating Amanita mushroom poisoning, this product is not readily available in the U.S. Details: Preliminary evidence from uncontrolled studies shows that administering silibinin, a constituent of milk thistle, intravenously (IV) within 48 hours of Amanita phalloides (death cap) mushroom poisoning, followed by oral therapy, may lessen liver damage (2615,63293). However, silibinin is not readily available in the US.
• Benign prostatic hyperplasia (BPH). Oral milk thistle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a milk thistle extract of silymarin 190 mg along with selenium 80 mcg orally three times daily for 6 months may improve lower urinary tract symptoms, urinary flow rates, and residual volumes in adults aged 45-70 years with BPH when compared with placebo (88155). It is unclear if these effects are due to milk thistle, selenium, or the combination.
• Beta-thalassemia. Meta-analyses of clinical studies in patients with beta-thalassemia suggest that oral silymarin, a constituent of milk thistle, reduces serum ferritin levels. Details: Most small clinical studies and meta-analyses of these studies show that taking silymarin in conjunction with conventional iron chelation medications such as deferiprone, deferasirox, or deferoxamine, is more effective for reducing serum ferritin levels than taking a conventional medication alone (88154,98452,107375). In one meta-analysis, the combination of silymarin and deferasirox appeared to be more effective than combinations with other iron chelation medications (107375). However, one preliminary clinical study in patients 12 years of age and older with beta-thalassemia shows that taking a milk thistle extract containing 70% to 80% silymarin (Legalon, Madaus GmbH) 140 mg orally three times daily for 3 months, in conjunction with deferoxamine, does not improve serum ferritin when compared with deferoxamine alone (63212). This difference in outcome is likely due to the shorter duration of therapy. Silymarin also does not seem to affect total iron binding capacity or liver iron concentration in patients with beta-thalassemia (107375).
• Chemotherapy-induced acral erythema. It is unclear if topical milk thistle is beneficial in patients with acral erythema due to capecitabine. Details: Preliminary clinical research shows that applying a gel containing a milk thistle extract of silymarin 1% twice daily to the hands and feet, starting from the first day of chemotherapy and continuing for 9 weeks thereafter, prolongs the time to onset of acral erythema and decreases its severity when compared with placebo in patients with gastrointestinal cancer who are receiving capecitabine for the first time (95022).
• Chemotherapy-induced hepatotoxicity. Results of clinical studies are mixed over whether oral milk thistle prevents or improves chemotherapy-induced hepatotoxicity. Details: One small clinical study in children and adults up to age 21 with acute lymphoblastic leukemia (ALL) and elevated liver function tests (LFTs) shows that taking a specific product containing the milk thistle constituent silibinin (Siliphos, Thorne Research, Inc.) 80-320 mg (depending on patient weight) daily for 28 days concurrently with chemotherapy does not improve LFTs or bilirubin levels when compared with placebo (63218). Another small clinical study in patients with non-metastatic breast cancer receiving doxorubicin, cyclophosphamide, and paclitaxel shows that taking a specific milk thistle extract of silymarin (Livergol, Goldaru Pharmaceutical Company) 140 mg three times daily with meals for 4 weeks does not improve fatty liver grading or LFTs when compared with placebo (105795). Conversely, a large clinical study in children aged 5-14 with elevated liver enzymes and receiving chemotherapy for ALL shows that taking silymarin 70 mg capsules twice daily or 50 mg syrup three times daily for 9 months modestly improves aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels, but does not improve alkaline phosphatase or albumin levels (113144). Similarly, observational research in patients with a variety of solid tumors and elevated LFTs due to chemotherapy or targeted therapy suggests that taking silymarin 150-900 mg daily is associated with reduced or stabilized LFTs in over half of patients; however, doses above 300-450 mg daily don't seem to have much more benefit (111176). The interpretation of these results is limited by the lack of a comparator group.
• Chemotherapy-induced nephrotoxicity. It is unclear if oral milk thistle is beneficial for the prevention of cisplatin-induced nephrotoxicity. Details: A small clinical study shows that taking a milk thistle extract standardized to 70% to 80% silymarin (Liverherb, Amin Pharmaceutical Company) 140 mg orally three times daily with meals, starting 24-48 hours before cisplatin and continuing until the end of three 21-day cycles, does not prevent cisplatin-induced nephrotoxicity when compared with placebo (95025).
• Cirrhosis. It is unclear if oral milk thistle extracts of silymarin are beneficial for cirrhosis from various causes. Details: Preliminary clinical research shows that taking a milk thistle extract of silymarin 420 mg orally daily for up to 4 years might improve liver function tests and decrease mortality in people with cirrhosis due to a variety of causes (2616,63145,63278,63340). However, a meta-analysis of clinical research evaluating milk thistle studies for the treatment of various liver diseases shows that effect sizes are generally small or lack statistical significance (63161).
• Contrast induced nephropathy. It is unclear if oral milk thistle is beneficial for reducing the risk of nephropathy from contrast agents. Details: Population research in Taiwanese patients with liver cirrhosis has found that taking silymarin daily for at least 90 days during a one-year period does not reduce the risk of contrast-induced nephropathy during the following four or more years (98453).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral milk thistle is beneficial for COVID-19. Details: Preliminary clinical research in adults hospitalized with COVID-19 requiring non-invasive oxygen support shows that taking a specific milk thistle product (SinaLive, Exir Nano Sina Company), 70 mg orally three times daily for 2 weeks, does not improve time to symptom resolution, lung scores, or length of stay when compared with placebo (109504).
• Critical illness (trauma). It is unclear if oral milk thistle is beneficial in critically ill patients with trauma-induced liver injury. Details: One small clinical study in patients admitted to the intensive care unit (ICU) due to trauma-induced liver injury shows that taking a specific milk thistle extract (Livergol, Goldaru Pharmaceutical Company) containing silymarin 140 mg three times daily for 14 days reduces markers of liver injury, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), when compared with placebo (105793). Whether this milk thistle extract improves morbidity, mortality, or length of ICU stay in these patients is unclear.
• Diabetic nephropathy. It is unclear if oral milk thistle is beneficial for improving kidney function in patients with this condition. Details: Preliminary clinical research in type 2 diabetic patients with diabetic nephropathy shows that taking a milk thistle extract of silymarin 140 mg orally three times daily for 3 months, in combination with conventional treatment decreases the urine albumin to creatinine ratio when compared with placebo. However, serum creatinine and estimated glomerular filtration rate are not improved (63250).
• Dyspepsia. Oral milk thistle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A specific combination product containing milk thistle (Iberogast, Medical Futures, Inc.) seems to improve symptoms of dyspepsia. The combination includes milk thistle plus peppermint leaf, German chamomile, caraway, licorice, clown's mustard plant, celandine, angelica, and lemon balm (19532). A meta-analysis of clinical research using this combination 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).
• Endometriosis. It is unclear if oral milk thistle is beneficial in patients with endometriosis. Details: Preliminary clinical research in females with ovarian endometrioma shows that taking a specific silymarin product (Goldaru Pharma) 140 mg twice daily for 12 weeks moderately improves pain scores, but not other sexual function scores, when compared with placebo (110486). However, some researchers have also recommended to avoid using milk thistle in estrogen-sensitive conditions, such as endometriosis, due to its estrogenic effects (93025,93026).
• Hepatitis. Small clinical studies suggest that oral milk thistle extracts of silymarin may improve hepatitis symptoms. It is unclear whether these products can improve liver function in these patients. Details: In people with hepatitis due to a variety of causes, taking a milk thistle extract containing 70% to 80% silymarin (Legalon, Madaus GmbH) 140 mg orally three times daily for 4 weeks reduces symptoms such as jaundice, dark urine, and scleral icterus, but does not improve liver function tests (LFTs) (63210,63317). However, some improvements in LFTs are seen with a silybin-phosphatidylcholine complex (Silipide, Inverni della Beffa Research and Development Laboratories) taken as 160-360 mg orally daily for 2 weeks to 3 months (63320,63321). However, there are methodological problems with these latter studies.
• Hepatitis B. Small clinical studies suggest that oral milk thistle extracts may improve liver function in people with hepatitis B, although it is unclear if these products can improve disease-related complications. Details: Preliminary clinical studies suggest that taking a milk thistle extract containing 70% to 80% silymarin (Legalon, Madaus GmbH) 140 mg orally three times daily for 28 days to one year, or a silybin-phosphatidylcholine complex (Silipide, Inverni della Beffa Research and Development Laboratories) 240 mg orally twice daily for 7 days, improves liver function tests (LFTs) and liver histology (7356,63263,63299). However, another study shows that taking a milk thistle extract of silymarin 140 mg orally three times daily for 5-25 days has no effect of LFTs (63288). A meta-analysis of clinical research and a review conclude that any clinical effect of milk thistle in people with viral hepatitis is very limited and results suggest that it lacks a significant effect on mortality, liver disease complications, or liver histology (17228,63192).
• Hepatitis C. Small clinical studies suggest that oral milk thistle extracts may improve liver function but do not seem to reduce hepatitis C virus (HCV) RNA levels. Details: Preliminary clinical studies show that taking a milk thistle extract containing 70% to 80% silymarin (Legalon, Madaus GmbH) 140 mg orally three times daily for 3-12 months, or a silybin-phosphatidylcholine complex (Silipide, Inverni della Beffa Research and Development Laboratories) 240 mg orally twice daily for 7 days, improves liver function tests (LFTs) and liver histology (7356,63299). However, other studies report that taking silymarin 125-140 mg three times daily for up to one year, 166 mg twice daily for 3 months, or 400 mg daily for 8 weeks does not improve serum HCV RNA levels, anti-HCV antibody levels, LFTs, or hepatomegaly (13170,63208,63247,63288,108658). Also, taking higher doses of silymarin, up to 700 mg three times daily for 6 months, does not have a significant effect on serum HCV RNA levels or LFTs when compared with placebo (63251). A meta-analysis of clinical research and a review conclude that any clinical effect of milk thistle in people with viral hepatitis is limited and most results show that milk thistle lacks a significant effect on mortality, liver disease complications, or liver histology (17228,63192,88156). Preliminary clinical research in adults with HCV-related advanced chronic liver disease shows that taking a specific milk thistle combination product containing silybinphospholipid complex 303 mg, vitamin D 10 mcg, and vitamin E 15 mg (Realsil 100 D, Ibi Lorenzini), twice daily for 12 months, improves liver stiffness scores, but not liver fibrosis scores, when compared with control (108659). It is unclear if this effect is due to milk thistle, other ingredients, or the combination.
• Hypercholesterolemia. Oral milk thistle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of three clinical trials in adults with hypercholesterolemia shows that taking a specific combination product (Berberol, PharmExtracta) containing milk thistle extract 105 mg and tree turmeric extract 588 mg twice daily for 3 months, along with diet and exercise, reduces levels of low-density lipoprotein (LDL) cholesterol by an average of 34 mg/dL when compared with diet and exercise alone. There was no effect on high-density lipoprotein (HDL) cholesterol or triglyceride levels (101158). The studies included in this meta-analysis are generally of low quality, lasted for no more than 12 months, and sometimes include patients with statin intolerance (95019,96140,101158). It is unclear if the effects of this product are due to milk thistle extract, tree turmeric extract, or the combination. Other clinical research shows that taking a similar product (Berberol K, PharmExtracta) containing milk thistle extract 105 mg, tree turmeric extract of berberine 500 mg, and monacolin K and KA 10 mg, taken once daily for 3 months along with diet and exercise, reduces levels of LDL cholesterol by about 28% when compared with diet and exercise alone in patients with hypercholesterolemia (97625). It is possible that any benefit of this product is due to the monacolin content.
• Hyperlipoproteinemia. It is unclear if oral milk thistle is beneficial in patients with hyperlipoproteinemia secondary to liver disease. Details: One very small crossover study shows that taking a milk thistle extract containing 70% to 80% silymarin (Legalon, Madaus GmbH) 420 mg orally daily for 7 months does not significantly improve cholesterol levels in patients with hyperlipoproteinemia secondary to liver disease when compared with placebo (63255).
• Hypoxic liver injury. It is unclear if oral milk thistle is beneficial for reducing liver injury in patients with hypoxia. Details: Preliminary clinical research in patients presenting to the emergency department with hypoxia shows that taking a milk thistle extract of silymarin 280 mg every 8 hours for 3 days reduces markers of liver injury, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT), when compared with placebo (103871).
• Infertility. It is unclear if oral milk thistle is beneficial for patients undergoing in vitro fertilization. Details: Preliminary clinical research shows that taking a milk thistle extract of silymarin 70 mg orally three times daily in combination with human chorionic gonadotropin (HCG) lowers the proportion of early and total apoptosis of follicle cells during in vitro fertilization due to male infertility. However, it does not have an effect on the number of oocytes retrieved or the thickness of the endometrium when compared with HCG plus placebo (63227).
• Lactation. It is unclear if oral milk thistle is beneficial for increasing milk production. Details: A small clinical study shows that taking a milk thistle extract standardized to 60% silymarin (BIO-C, Milte Italia S.r.l.) 240 mg twice daily for 4 weeks does not increase milk production when compared with placebo in mothers of preterm newborns (95027).
• Melasma. It is unclear if topical milk thistle is beneficial in patients with melasma. Details: Preliminary clinical research in adults with melasma shows that applying silymarin 1.4% cream twice daily for 3 months moderately improves melasma appearance scores when compared to baseline. These improvements were similar to hydroquinone cream 2% (110489). One small clinical trial in females with melasma shows that application of silymarin 1.4% cream twice daily to the affected area for 3 months is as effective for improving melasma area and severity as a specific type of laser therapy (low fluence Q switched ND:YAG 1064 nm) (105791).
• Menopausal symptoms. It is unclear if oral milk thistle reduces menopausal symptoms such as hot flashes. Details: One small clinical study in postmenopausal patients shows that taking milk thistle fruit extract 200 mg, containing 80% silymarin, twice daily for 8 weeks seems to reduce the number and severity of daily hot flashes and overall climacteric symptoms when compared with taking placebo (105053). This finding is limited by incomplete reporting and potentially inadequate blinding. Other preliminary clinical research has evaluated milk thistle in combination with black cohosh, dong quai, red clover, American ginseng, and chasteberry (Phyto-Female, SupHerb), with some evidence of benefit for reducing hot flashes and night sweats. (19552).
• Metabolic syndrome. Oral silymarin, a constituent of milk thistle, seems to improve some of the laboratory abnormalities associated with metabolic syndrome. Details: A meta-analysis of 11 low-quality clinical trials in adults with metabolic syndrome, conducted in Asia and Africa, shows that silymarin, 140-2100 mg daily for 45 days to 12 months, modestly reduces fasting blood glucose, glycated hemoglobin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, and increases high-density lipoprotein cholesterol levels, when compared with placebo (107374).
• Multiple sclerosis (MS). Oral milk thistle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with MS shows that taking a supplement containing a milk thistle extract of silymarin 150 mg in combination with ferulic acid, gamma-oryzanol, and apigenin twice daily for 3-24 months may stabilize clinical symptoms of MS when compared to baseline (63223). It is unclear if this effect is due to milk thistle, other ingredients, or the combination.
• Nonalcoholic fatty liver disease (NAFLD). Small clinical studies suggest that oral milk thistle extracts of silymarin may slightly improve markers of liver function patients with NAFLD. Details: Two meta-analyses of small clinical trials in patients with NAFLD show that taking milk thistle products containing a total of silymarin 140-2100 mg daily, either alone or in combination with other ingredients, for 8-48 weeks reduces aspartate aminotransferase (AST) by 7 IU/L and alanine aminotransferase (ALT) by 9-15 IU/L, but does not affect weight or lipid levels, when compared with control (97622,105051). However, these changes in liver enzymes may not be clinically impactful and some experts note that serum AST levels do not reliably reflect the spectrum of liver histology in patients with NAFLD (98130). Preliminary clinical research in adults with NAFLD and a body-mass index (BMI) of at least 35 kg/m2 shows that taking milk thistle extract 140 mg 4 times daily for 8 weeks, in addition to lifestyle modifications, reduces BMI by approximately 1 kg/m² when compared with placebo with lifestyle modifications (108657). However, another small clinical trial in adults with NAFLD and a BMI of at least 40 kg/m2 shows that taking a specific silymarin product (Livergol, Goldaru Pharmaceuticals) 140 mg three times daily for 4 weeks did not reduce BMI or improve liver enzymes, such as AST and ALT, when compared with placebo (110484). One small clinical study in patients with NAFLD shows that taking a specific combination product (Eurosil 85, MEDAS SL) containing milk thistle extract standardized to silymarin 540 mg and vitamin E 36 mg daily for 3 months, in addition to following a low-calorie diet, does not appear to improve NAFLD-Fibrosis score or fatty liver index (FLI) when compared with following a low-calorie diet alone (96261).
• Nonalcoholic steatohepatitis (NASH). It is unclear if oral milk thistle is beneficial in patients with NASH. Details: Clinical research in patients with NASH shows that taking a milk thistle extract of silymarin 700 mg three times daily for 48 weeks improves fibrosis in more patients when compared with placebo (96107). However, there is no significant between-group difference in global histological improvement with this product (96107) or with a specific silymarin product (Legalon, Rottapharm Madaus, Mylan) 420 or 700 mg three times daily for 48-50 weeks (101150).
• Obsessive-compulsive disorder (OCD). It is unclear if oral milk thistle is beneficial in patients with OCD. Details: Preliminary clinical research shows that taking milk thistle leaf extract 200 mg orally three times daily for 8 weeks has a limited effect on OCD symptom scores when compared to baseline, but does not provide any benefit over fluoxetine 10 mg three times daily (63219).
• Parkinson disease. Oral milk thistle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a supplement containing a milk thistle extract of silymarin 150 mg in combination with ferulic acid, gamma-oryzanol, and apigenin orally twice daily for 3 months to 24 months may stabilize clinical symptoms in patients with Parkinson disease when compared to baseline (63223). It is unclear if this effect is due to milk thistle, other ingredients, or the combination.
• Postpartum complications. It is unclear if topical milk thistle is beneficial in postpartum patients with an episiotomy. Details: Preliminary clinical research in postpartum patients shows that applying milk thistle 3% in Eucerin ointment twice daily to the suture site for 10 days reduces episiotomy pain and improves the healing rate when compared with placebo. The milk thistle product was prepared with an ethanolic extract of the seeds to provide 1.53% silybin (107373).
• Prostate cancer. Oral milk thistle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with a history of prostate cancer who have had radiotherapy or radical prostatectomy shows that taking a dietary supplement containing a milk thistle extract of silymarin 160 mg, soy isoflavones (Novasoy, ADM) 62.5 mg, lycopene (Lyc-O-Mato, LycoRed Natural Products Industries, Ltd.) 15 mg, vitamins, minerals, and antioxidants orally daily for 10 weeks increases the time it takes for prostate-specific antigen (PSA) levels to double by 2.6-fold when compared with placebo (60361).
• Radiation dermatitis. It is unclear if topical milk thistle is beneficial in patients with dermatitis due to radiation. Details: Preliminary clinical research in females with breast cancer undergoing radiotherapy shows that applying a specific topical product containing a milk thistle extract of silymarin (Leviaderm, Madaus GmbH) significantly reduces the incidence of radiation dermatitis and prolongs the time to the onset of radiation dermatitis when compared with applying a panthenol-containing cream (63239).
• Radiation mucositis. It is unclear if oral milk thistle is beneficial for preventing or treating mucositis due to radiation. Details: One small clinical study in patients with head and neck cancer receiving radiotherapy for the first time shows that taking a specific product containing a milk thistle extract of silymarin (Livergol, Goldaru Pharmaceutical Company), 140 mg three times daily starting from the first day of radiotherapy and continuing for 6 weeks thereafter, reduces the severity and prolongs the time to onset of radiation-induced mucositis when compared with placebo (95021).
• Toxin-induced liver damage. Most small clinical studies suggest that oral milk thistle extracts or constituents may reduce liver injury in people exposed to some, but not all, toxins and medications known to cause liver damage. Details: Taking a milk thistle extract containing 70% to 80% silymarin (Legalon, Madaus GmbH) 420 mg orally daily for up to one month improves liver function tests (LFTs) in people with abnormal LFTs due to chronic occupational exposure to paints or organic solvents such as toluene or xylene (2614,63280). Milk thistle extract has also shown some benefit for reducing drug-induced liver injury (DILI). In patients on isotretinoin therapy for acne, taking a specific milk thistle extract containing silymarin (Livergol, Goldaru Pharmaceutical Company) 140 mg daily for 30 days improves LFTs when compared with placebo (102852). A small clinical study in patients with relapsing-remitting multiple sclerosis who were initiating therapy with fingolimod shows that taking a specific milk thistle extract (Livergol, Goldaru Pharmaceutical Company) containing silymarin 140 mg daily for 6 months prevents fingolimod-induced LFT elevations when compared with placebo (105794). In patients receiving treatment for tuberculosis with rifampin, isoniazid, pyrazinamide, ethambutol, and streptomycin, taking the milk thistle constituent silibinin 70 mg orally three times daily for 6-12 months reduces the rate of liver toxicity to 14% compared with 53% in patients taking glucuronolactone 200 mg orally three times daily (63224). Additionally, in patients receiving standard treatment for tuberculosis with isoniazid, rifampicin, pyrazinamide, and ethambutol, taking a milk thistle extract of silymarin 140 mg orally three times daily for 4 weeks decreases the risk of DILI by 28% when compared with placebo. About 1 in every 4 patients who take silymarin for 4 weeks would avoid DILI (95024). A small clinical study in Iran, also in adults receiving standard treatment for tuberculosis, shows that taking a milk thistle extract of silymarin 150 mg twice daily for 2 weeks modestly improves LFTs when compared with control. None of the 16 patients in the silymarin group developed DILI compared with 2 of 21 patients in the control group; however, this finding was not statistically significant (112230). The interpretation of these findings is limited by the short study duration. However, taking a milk thistle extract of silymarin 420 mg orally daily for 3 months does not seem to prevent liver toxicity associated with tacrine (Cognex) therapy in people with Alzheimer disease (63140). Other research in people with elevated LFTs due to long-term therapy with phenothiazine or butyrophenone antipsychotic medications shows that taking silymarin 800 mg orally daily for 3 months also does not improve LFTs when compared with placebo (63344). A retrospective study in patients with DILI of various offending agents has also found that taking a milk thistle extract, containing a median of 450 mg silybin daily for 24 days is associated with 1.7-2.8 times higher likelihood of LFT normalization when compared with control (110485).
• Trichotillomania. It is unclear if oral milk thistle is beneficial in patients with this condition. Details: Preliminary clinical research in patients 12-65 years of age shows that taking milk thistle 150 mg twice daily for 2 weeks, and then 300 mg twice daily for 4 weeks, does not improve symptoms of trichotillomania when compared with placebo (99426).
• Ulcerative colitis. It is unclear if oral milk thistle is beneficial in patients with this condition. Details: Preliminary clinical research in patients 16-75 years of age shows that taking a specific milk thistle extract of silymarin (Livergol, Goldaru Pharmaceutical Company) 140 mg daily for 6 months, in conjunction with standard medications, decreases disease activity and helps maintain remission when compared with placebo in patients with ulcerative colitis (95029).
• Vitiligo. It is unclear if oral milk thistle reduces the severity of this condition. Details: Preliminary clinical research in a small number of patients with vitiligo shows that taking a specific milk thistle extract containing silymarin (Livergol, Goldaru Pharmaceutical Company) 140 mg twice daily along with phototherapy for 3 months does not improve the severity of vitiligo when compared with phototherapy plus placebo (102851). More evidence is needed to rate milk thistle for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Angina. It is unclear if oral Terminalia arjuna is beneficial in patients with angina. Details: Low-quality clinical research in patients with angina shows that taking Terminalia arjuna extract 500-2000 mg orally daily for 3 months reduces the frequency of angina symptoms by 50% to 71% when compared with baseline. These results were similar to taking conventional therapy (2502,2503). Other preliminary research in adults with chronic stable angina shows that taking Terminalia arjuna 500 mg orally three times daily for 7 days reduces the need for rescue treatment and improves exercise tolerance when compared with placebo. Improvements were similar to taking isosorbide mononitrate 20 mg twice daily (92833).
• Asthma. Although there has been interest in using oral Terminalia arjuna for asthma, there is insufficient reliable information about the clinical effects of Terminalia arjuna for this purpose.
• Athletic performance. It is unclear if oral Terminalia arjuna is beneficial for athletic performance. Details: A small clinical study in young regular exercising males shows that taking Terminalia arjuna extract (Oxyjun, Enovate Biolife Pvt Ltd, India) 400 mg daily for 8 weeks increases the time to exhaustion by approximately 117 seconds when compared with placebo. There were also modest improvements in feelings of perceived exertion and the left ventricular ejection fraction, a measure of blood pumped from the heart with each heartbeat (111093). It is unclear if oral Terminalia arjuna is beneficial other populations such as athletes and females.
• Coronary heart disease (CHD). It is unclear if oral Terminalia arjuna is beneficial in patients with CHD. Details: Preliminary clinical research in patients with CHD shows that taking Terminalia arjuna bark powder 500 mg orally daily for 30 days decreases levels of total cholesterol by about 10% and low-density lipoprotein (LDL) cholesterol by about 16% when compared with baseline. Taking Terminalia arjuna bark powder did not improve high-density lipoprotein (HDL) cholesterol levels (92832).
• Heart failure. The effects of Terminalia arjuna in patients with heart failure is unclear; evidence to date comes from small, short-term clinical studies, and results are conflicting. Details: Preliminary, low-quality clinical research in patients with severe, refractory congestive heart failure shows that taking Terminalia arjuna bark extract 500 mg orally three times daily for 2 weeks, as an adjunct to conventional therapy, improves left ventricular ejection fraction (LVEF) by 17% when compared with placebo (2504). However, other preliminary clinical research in adults with stage II heart failure shows that taking an extract of Terminalia arjuna bark 750 mg orally twice daily as an adjunct to conventional therapy for 12 weeks does not improve LVEF, functional class, or functional capacity when compared with placebo (96726). However, the validity of these trials is limited by short-term treatment and variation in the conventional therapies used to manage heart failure.
• Hyperlipidemia. It is unclear if oral Terminalia arjuna is beneficial for improving lipid levels. Details: Preliminary clinical research in patients with elevated cardiovascular risk factors, such as hypertension, dyslipidemia, or obesity, shows that taking Terminalia arjuna 5 grams orally twice daily for 60 days decreases levels of low-density lipoprotein (LDL) cholesterol and triglycerides by 17% and 35%, respectively, and increases high-density lipoprotein (HDL) cholesterol levels by 9%, when compared with baseline. Improvements in lipid parameters were similar to taking amlodipine 5 mg and atorvastatin 10 mg daily (109677). However, this study may have been inadequately powered to detect a difference between groups.
• Hypertension. It is unclear if oral Terminalia arjuna is beneficial for reducing blood pressure. Details: Preliminary clinical research in patients with elevated cardiovascular risk factors such as hypertension, dyslipidemia, or obesity, shows that taking Terminalia arjuna 5 grams orally twice daily for 60 days reduces systolic and diastolic blood pressure by 11% and 14%, respectively, when compared with baseline. Improvements in blood pressure were similar to taking amlodipine 5 mg and atorvastatin 10 mg daily (109677). However, this study may have been inadequately powered to detect a difference between groups.
• Obesity. It is unclear if oral Terminalia arjuna is beneficial for weight loss. Details: Preliminary clinical research in patients with elevated cardiovascular risk factors, such as hypertension, dyslipidemia, or obesity, shows that taking Terminalia arjuna 5 grams orally twice daily for 60 days reduces body mass index (BMI) by 6% when compared with baseline. Improvements in BMI were similar to taking amlodipine 5 mg and atorvastatin 10 mg daily (109677). This study may have been inadequately powered to detect a difference between groups. More evidence is needed to rate Terminalia arjuna for these uses.

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

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those in foods.

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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.

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LIKELY SAFE ...when used orally and appropriately. A specific milk thistle extract standardized to contain 70% to 80% silymarin (Legalon, Madaus GmbH) has been safely used in doses up to 420 mg daily for up to 4 years (2613,2614,2616,7355,63210,63212,63278,63280,63299,63340)(88154,97626,105792). Higher doses of up to 2100 mg daily have been safely used for up to 48 weeks (63251,96107,101150). Another specific milk thistle extract of silymarin (Livergol, Goldaru Pharmaceutical Company) has been safely used at doses of 140 mg daily for up to 6 months and doses of 420 mg daily for up to 6 weeks (95021,95029,102851,102852,105793,105794,105795). Some isolated milk thistle constituents also appear to be safe. Silibinin (Siliphos, Thorne Research) has been used safely in doses up to 320 mg daily for 28 days (63218). Some combination products containing milk thistle and other ingredients also appear to be safe. A silybin-phosphatidylcholine complex (Silipide, Inverni della Beffa Research and Development Laboratories) has been safely used in doses of 480 mg daily for 7 days (7356) and 240 mg daily for 3 months (63320). Tree turmeric and milk thistle capsules (Berberol, PharmExtracta) standardized to contain 60% to 80% silybin have been safely used twice daily for up to 12 months (95019,96140,96141,96142,97624,101158).

POSSIBLY SAFE ...when used topically and appropriately, short-term. A milk thistle extract cream standardized to silymarin 0.25% (Leviaderm, Madaus GmbH) has been used safely throughout a course of radiotherapy (63239). Another milk thistle extract cream containing silymarin 1.4% has been used with apparent safety twice daily for 3 months (105791,110489). A cream containing milk thistle fruit extract 25% has been used with apparent safety twice daily for up to 12 weeks (111175). A milk thistle extract gel containing silymarin 1% has been used with apparent safety twice daily for 9 weeks (95022). There is insufficient reliable information available about the safety of intravenous formulations of milk thistle or its constituents.

PREGNANCY AND LACTATION:
While research in an animal model shows that taking milk thistle during pregnancy and lactation does not adversely impact infant development (102850), there is insufficient reliable information available about its safety during pregnancy or lactation in humans; avoid using.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. A milk thistle extract 140 mg three times daily has been used with apparent safety for up to 9 months (88154,98452). A specific product containing the milk thistle constituent silybin (Siliphos, Thorne Research Inc.) has been used with apparent safety in doses up to 320 mg daily for up to 4 weeks in children one year of age and older (63218).

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POSSIBLY SAFE ...when used orally and appropriately, short-term. Several small studies have used Terminalia arjuna powdered bark or bark extract with apparent safely in doses up to 2000 mg or 400 mg daily, respectively, for 2 weeks to 3 months (2502,2503,2504,111012,111093); however, patients should avoid self-treatment with this product due to potentially significant cardiovascular effects. Further study is needed to determine the safety of Terminalia arjuna for long-term use.

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

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking dandelion root along with anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.  Details In vitro research suggests that dandelion root inhibits platelet aggregation (18291).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the risk for hypoglycemia when used with antidiabetes drugs.  Details Laboratory research suggests that dandelion extract may have moderate alpha-glucosidase inhibitor activity and might also increase insulin secretion (13474,90926). Also, in a case report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemia 2 weeks after beginning to eat salads containing dandelion (46960).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase levels of drugs metabolized by CYP1A2.  Details Laboratory research suggests that dandelion might inhibit CYP1A2 (12734). So far, this interaction has not been reported in humans. However, until more is known, watch for an increase in the levels of drugs metabolized by CYP1A2 in patients taking dandelion.

GLUCURONIDATED DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the clearance of drugs that are UDP-glucuronosyltransferase substrates.  Details There is some preliminary evidence that dandelion might induce UDP-glucuronosyltransferase, a phase II enzyme (12734).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, through diuretic effects, dandelion might reduce excretion and increase levels of lithium.  Details Animal research suggests that dandelion has diuretic properties (13475). As diuretics can increase serum lithium levels, the dose of lithium might need to be decreased when taken with dandelion.

POTASSIUM-SPARING DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.  Details Dandelion contains significant amounts of potassium (13465).

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might lower fluoroquinolone levels.  Details Animal research shows that dandelion reduces absorption of ciprofloxacin and can lower levels by 73% (13477). However, this effect has not been reported in humans.

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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).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Taking milk thistle with antidiabetes drugs may increase the risk of hypoglycemia.  Details Clinical research shows that milk thistle extract, alone or along with tree turmeric extract, can lower blood glucose levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, including those already taking antidiabetes drugs (15102,63190,63314,63318,95019,96140,96141,97624,97626).

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, milk thistle might inhibit CYP2B6.  Details An in vitro study shows that silybin, a constituent of milk thistle, binds to and noncompetitively inhibits CYP2B6. Additionally, silybin might downregulate the expression of CYP2B6 by decreasing mRNA and protein levels (112229).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = B It is unclear if milk thistle inhibits CYP2C9; research is conflicting.  Details In vitro research suggests that milk thistle might inhibit CYP2C9 (7089,17973,17976). However, contradictory clinical research shows that milk thistle extract does not inhibit CYP2C9 or significantly affect levels of the CYP2C9 substrate tolbutamide (13712,95026). Differences in results could be due to differences in dosages or formulations utilized (95026).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = D It is unclear if milk thistle inhibits CYP3A4; research is conflicting.  Details While laboratory research shows conflicting results (7318,17973,17975,17976), pharmacokinetic research shows that taking milk thistle extract 420-1350 mg daily does not significantly affect the metabolism of the CYP3A4 substrates irinotecan, midazolam, or indinavir (8234,17974,93578,95026).

ESTROGENS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, milk thistle might interfere with estrogen therapy through competition for estrogen receptors.  Details Animal research suggests that a milk thistle extract of silymarin binds to estrogen receptor beta (93025,93026).

GLUCURONIDATED DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.  Details Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation (7318,17973). Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase (7354), although the significance of this effect is unclear.

HMG-CoA REDUCTASE INHIBITORS ("Statins") Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, milk thistle might interfere with statin therapy by decreasing the activity of organic anion transporting polypeptide 1B1 (OATB1B1) and inhibiting breast cancer resistance protein (BCRP).  Details Preliminary evidence suggests that a milk thistle extract of silymarin can decrease the activity of the OATP1B1, which transports HMG-CoA reductase inhibitors into the liver to their site of action. The silibinin component also inhibits BCRP, which transports statins from the liver into the bile for excretion. However, in a preliminary study in healthy males, silymarin 140 mg three times daily had no effect on the pharmacokinetics of a single 10 mg dose of rosuvastatin (16408).

INDINAVIR (Crixivan) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, milk thistle may induce cytochrome P450 3A4 (CYP3A4) enzymes and increase the metabolism of indinavir; however, results are conflicting.  Details One pharmacokinetic study shows that taking milk thistle (Standardized Milk Thistle, General Nutrition Corp.) 175 mg three times daily in combination with multiple doses of indinavir 800 mg every 8 hours decreases the mean trough levels of indinavir by 25% (8234). However, results from the same pharmacokinetic study show that milk thistle does not affect the overall exposure to indinavir (8234). Furthermore, two other pharmacokinetic studies show that taking specific milk thistle extract (Legalon, Rottapharm Madaus; Thisilyn, Nature's Way) 160-450 mg every 8 hours in combination with multiple doses of indinavir 800 mg every 8 hours does not reduce levels of indinavir (93578).

LEDIPASVIR Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, milk thistle might increase the levels and clinical effects of ledipasvir.  Details Animal research in rats shows that milk thistle increases the area under the curve (AUC) for ledipasvir and slows its elimination (109505).

MORPHINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of milk thistle with morphine might affect serum levels of morphine and either increase or decrease its effects.  Details Animal research shows that milk thistle reduces serum levels of morphine by up to 66% (101161). In contrast, laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation (7318,17973). Theoretically, this could decrease the clearance and increase morphine levels. The effect of taking milk thistle on morphine metabolism in humans is not known.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.  Details Although in vitro research shows that milk thistle can inhibit P-glycoprotein activity (95019), clinical research does not agree. A small pharmacokinetic study in healthy volunteers shows that taking milk thistle (Enzymatic Therapy Inc.) 900 mg, standardized to 80% silymarin, in 3 divided doses daily for 14 days does not affect absorption of digoxin, a P-glycoprotein probe substrate (35825).

RALOXIFENE (Evista) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, milk thistle might decrease the clearance and increase levels of raloxifene.  Details Laboratory research suggests that the milk thistle constituents silibinin and silymarin inhibit the glucuronidation of raloxifene in the intestines (93024).

SIROLIMUS (Rapamune) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Milk thistle might decrease the clearance of sirolimus.  Details Pharmacokinetic research shows that a milk thistle extract of silymarin decreases the apparent clearance of sirolimus in hepatically impaired renal transplant patients (19876). It is unclear if this interaction occurs in patients without hepatic impairment.

SOFOSBUVIR (Solvaldi) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, milk thistle might decrease the levels and clinical effects of sofosbuvir.  Details Animal research in rats shows that milk thistle reduces the metabolism of sofosbuvir, as well as the hepatic uptake of its active metabolite (109505).

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, the milk thistle constituent silibinin might increase tamoxifen levels and interfere with its conversion to an active metabolite.  Details Animal research suggests that the milk thistle constituent silibinin might increase plasma levels of tamoxifen and alter its conversion to an active metabolite. The mechanism appears to involve inhibition of pre-systemic metabolism of tamoxifen by cytochrome P450 (CYP) 2C9 and CYP3A4, and inhibition of P-glycoprotein-mediated efflux of tamoxifen into the intestine for excretion (17101). Whether this interaction occurs in humans is not known.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, milk thistle might increase the effects of warfarin.  Details In one case report, a man stabilized on warfarin experienced an increase in INR from 2.64 to 4.12 after taking a combination product containing milk thistle 200 mg daily, as well as dandelion, wild yam, niacinamide, and vitamin B12. Levels returned to normal after stopping the supplement (101159). Although a direct correlation between milk thistle and the change in INR cannot be confirmed, some in vitro research suggests that milk thistle might inhibit cytochrome P450 2C9 (CYP2C9), an enzyme involved in the metabolism of various drugs, including warfarin (7089,17973,17976).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Terminalia arjuna with anticoagulant or antiplatelet drugs may increase the risk of bleeding in some patients.  Details In vitro, Terminalia arjuna bark extract inhibits platelet aggregation, decreases platelet activation, and shows antithrombotic properties (92831).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of Terminalia arjuna may increase the levels and clinical effects of CYP2C9 substrates.  Details In vitro research shows that Terminalia arjuna extract inhibits CYP2C9 enzymes and reduces CYP2C9 substrate metabolism (96729).

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of Terminalia arjuna may increase the levels and clinical effects of CYP2D6 substrates.  Details In vitro research shows that Terminalia arjuna extract inhibits CYP2D6 enzymes and reduces CYP2D6 substrate metabolism (96729).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of Terminalia arjuna may increase the levels and clinical effects of CYP3A4 substrates.  Details In vitro research shows that Terminalia arjuna extract inhibits CYP3A4 enzymes and reduces CYP3A4 substrate metabolism (96729).

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General ...Orally, dandelion seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, heartburn, and stomach discomfort.
Topically: Dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.

Cardiovascular ...In one report, a 39-year-old obese woman developed palpitations and syncope after taking a weight loss supplement containing a combination of dandelion, bladderwrack, and boldo for 3 weeks. The patient was found to have prolonged QT-interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether dandelion, another ingredient, or the combination of ingredients is responsible for this adverse effect. The product was not analyzed to determine the presence of any potential toxic contaminants.

Dermatologic ...Topically, dandelion can cause contact dermatitis and erythema multiforme in sensitive individuals. Dandelion can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family (13478,13481,42893,46945,46977). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Endocrine ...In one report, a 56-year-old man with renal impairment developed hyperoxalaemia and peripheral gangrene after ingesting large amounts of dandelion tea (10 to 15 cups daily for 6 months). The adverse effect was attributed to the high oxalate content of dandelion tea (258 mcmol/L) and reduced renal oxalate clearance caused by renal impairment (90639). In another report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemic symptoms 2 weeks after beginning to eat salads containing dandelion (46960). The hypoglycemic effect was attributed to the potential alpha-glucosidase inhibitory activity of dandelion.

Gastrointestinal ...Gastrointestinal symptoms, including stomach discomfort, diarrhea, and heartburn, have been reported following oral use of dandelion (19146,36931). A case of intestinal blockage has been reported for a patient who ingested a large amount of dandelion greens three weeks after undergoing a stomach operation (46981). Also, a case of hemorrhagic cystitis has been reported for a 33-year-old woman who took a specific herbal product (Slim-Kombu, Balestra and Mech, Vicenza, Italy) containing 20 herbal extracts, including dandelion extract. Symptoms resolved after the patient discontinued using the product, and symptoms resumed when the patient began taking the supplement again four months later. While various ingredients in the supplement may have contributed to the symptoms, it is possible that dandelion extract may have contributed to the effect due to its diurectic, laxative, cholagogue, and antirheumatic properties (46959).

Other ...Orally, products containing dandelion pollen can cause allergic reactions, including anaphylaxis (13479,13480). Also, rhinoconjunctivitis and asthma have been reported after handling products such as bird feed containing dandelion and other herbs, with reported positive skin tests for dandelion hypersensitivity (46948). Dandelion pollen may cause pollinosis, such as allergic rhinitis and conjunctivitis (18065,46951,46964,46966,46972).

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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).

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General ...Orally, milk thistle is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal bloating, diarrhea, dyspepsia, flatulence, and nausea. However, these adverse effects do not typically occur at a greater frequency than with placebo.
Serious Adverse Effects (Rare):
Orally: Allergic reactions, including anaphylaxis, have been reported.

Dermatologic ...Orally, milk thistle may cause allergic reactions including urticaria, eczema, skin rash, and anaphylaxis in some people (6879,7355,8956,63210,63212,63238,63251,63315,63325,95029). Allergic reactions may be more likely to occur in patients sensitive to the Asteraceae/Compositae family (6879,8956). A case report describes a 49-year-old female who developed clinical, serologic, and immunopathologic features of bullous pemphigoid after taking milk thistle orally for 6 weeks. Symptoms resolved after treatment with prednisone and methotrexate (107376). Topically, milk thistle can cause erythema (110489).

Gastrointestinal ...Mild gastrointestinal symptoms have been reported, including nausea, vomiting, bloating, diarrhea, epigastric pain, abdominal colic or discomfort, dyspepsia, dysgeusia, flatulence, constipation, and loss of appetite (2616,6879,8956,13170,63140,63146,63160,63210,63218,63219)(63221,63244,63247,63250,63251,63320,63321,63323,63324,63325)(63327,63328,95024,95029,107374). There is one report of a 57-year-old female with sweating, nausea, colicky abdominal pain, diarrhea, vomiting, weakness, and collapse after ingesting milk thistle; symptoms subsided after 24-48 hours without medical treatment and recurred with re-challenge (63329).

Musculoskeletal ...In one clinical study three patients taking milk thistle 200 mg orally three times daily experienced tremor; the incidence of this adverse effect was similar for patients treated with fluoxetine 10 mg three times daily (63219).

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General ...There is currently a limited amount of information available on the adverse effects of oral Terminalia arjuna. A thorough evaluation of safety outcomes has not been conducted.

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