Keep It Movin' Plum Berry by OLLY

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

• Menopausal symptoms. Oral rhubarb root extract seems to help improve symptoms of menopause. Details: Clinical research in perimenopausal and postmenopausal patients shows that taking a specific dry extract of rhubarb root (ERr 731, Estroease, Lupin Pharmaceuticals) 4 mg orally daily for 3-27 months improves symptoms of menopause by 46% to 83% compared to an improvement of less than 20% with placebo. About 83% of females taking the rhubarb extract report overall clinical improvement, with specific improvements in anxiety, hot flushes, sweating, sleep, mood, quality of life, fatigue, sexual problems, urinary tract problems, vaginal dryness, and joint and muscle issues (92294,92295,92296,92297,92298,108960).
• Pancreatitis. Oral or rectal rhubarb might improve symptoms and duration of hospital stay in individuals with acute pancreatitis. It is unclear if oral rhubarb helps to prevent pancreatitis in individuals undergoing endoscopic retrograde cholangiopancreatography (ERCP). Details: Meta-analyses of clinical research in adults with acute pancreatitis in China shows that administering rhubarb 10-90 grams daily via gastric tube or rectal enema for 3-14 days, in combination with somatostatin, octreotide, or ulinastatin, reduces the risk for complications such as sepsis or kidney failure by 45%, duration of abdominal pain by 1.3-2 days, and duration of hospital stay by 6.7-6.9 days when compared with taking these medications alone (97922,100964). However, the included studies were of low methodological quality. Additionally, somatostatin and octreotide are not recommended for the treatment of acute pancreatitis by the American College of Gastroenterology or the American Gastroenterological Association (101001,100965). A separate meta-analysis and individual clinical studies show that administering rhubarb 6-20 grams 1-3 times daily for 5-14 days, usually via nasojejunal tube with early enteral nutrition, reduces the duration of hospital stay and improves abdominal symptoms when compared with enteral nutrition alone (92301,103475). The meta-analysis shows that administering rhubarb reduces hospital stay by 4.5 days and intensive care unit stay by 2.8 days. The use of rhubarb also reduced the duration of severe abdominal pain, abdominal distention, and abnormal bowel sounds by 1-2 days. However, there was no effect on mortality rate, infection rate, or the incidence of multiple organ dysfunction (103475). Rhubarb has also been studied for the prevention of pancreatitis in patients undergoing a specific procedure called endoscopic retrograde cholangiopancreatography (ERCP). Preliminary clinical research in patients at high risk for post-ERCP complications shows that drinking a raw rhubarb solution after the procedure reduces the incidence of post-ERCP pancreatitis by 74% and post-ERCP hyperamylasemia by 81% when compared to standard care. However, this study was of low methodological quality, and the rhubarb solution preparation and dose were not reported (97920).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acute respiratory distress syndrome (ARDS). It is unclear if oral rhubarb reduces ARDS. Details: A small clinical study in patients with ARDS shows that administering rhubarb leachate 10 grams in 30 mL water via nasogastric tube three times daily for 7 days, in addition to standard treatment, modestly improves oxygenation and reduces indices of pulmonary vascular permeability when compared with standard treatment (97921).
• Appendicitis. Oral rhubarb has only been evaluated in combination with other ingredients for use in pediatric appendiceal abscess; its effect when used alone is unclear. Details: A large observational study in children 3-14 years old with appendiceal abscess also receiving intravenous antibiotics suggests that taking a rhubarb peony decoction twice daily for 7-14 days is associated with a higher clinical cure rate of 93% when compared with 81% in the control group, but does not improve length of stay, post-operative complications, or recurrence rate (112380). However, it is unclear if the effects are from rhubarb, other ingredients, or the combination.
• Canker sores. Topical rhubarb has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small open-label clinical study in adults with mild canker sores shows that topical application of a specific combination product (Pyralvex Soluté, Laboratoires Norgine Pharma) containing rhubarb extract 5% and salicylic acid reduces the time to symptom resolution by about 3 days when compared to using a water control (97919).
• Chronic kidney disease (CKD). It is unclear if oral rhubarb prevents the progression of CKD or improves markers of kidney function. Details: A meta-analysis of results from two low-quality clinical studies shows that taking rhubarb 1-7.7 grams daily for up to 48 months as part of traditional Chinese medicine does not delay the onset of kidney failure when compared with standard treatment (92302). However, these results were calculated using regression analysis rather than long-term follow-up, which limits the validity of these findings. Another meta-analysis of clinical research shows that rhubarb may improve serum creatinine and blood urea nitrogen in patients with CKD when compared with no treatment (92302). However, rhubarb does not appear to improve blood urea nitrogen when compared with captopril (71329). The validity of the research to date is limited by the low to very low methodological quality of the studies and the high risk of bias. Additionally, all of the studies were conducted in China; it is unclear if these findings are applicable to other populations.
• Constipation. It is unclear if rhubarb is beneficial for constipation. Details: A small clinical study in middle-aged adults with constipation shows that taking rhubarb extract 12.5 mg or 25 mg based on rhein content (Gutisrheum, Laboratories Ortis) at bedtime for 1 month improves stool frequency and consistency when compared with placebo (112381). The validity of these findings is limited by patient-reported outcomes. A clinical study in patients with chronic constipation, defined as having a bowel movement no more than twice per week, shows that a specific combination product (Nucarb; Wilshire Laboratories Ltd) containing rhubarb extract 250 mg, activated charcoal 180 mg, calcium sennosides 50 mg, peppermint oil 0.5 mg, fennel oil 0.5 mg, and sulfur 50 mg, taken as two tablets at bedtime for one week, followed by 1 tablet at bedtime for 1 week, reduces passing gas, abdominal pain, and sensation of bloating by 81%, 73%, and 72% respectively, when compared with baseline. Sensation of straining, severity of constipation, and feeling of incomplete evacuation were reduced by 69%, 67%, and 54% respectively, when compared with baseline (108853). The validity of these findings is limited by the lack of a comparator group, and it is unclear whether the effects are due to rhubarb, the combination, or other ingredients.
• Dysmenorrhea. It is unclear if oral rhubarb reduces dysmenorrhea. Details: Preliminary clinical research in young adults with dysmenorrhea shows that taking rhubarb root and rhizome powder 2520 mg daily, beginning 2 days before menstruation and continuing for 5 days, repeated for three consecutive cycles, has similar efficacy to mefenamic acid 500 mg three times daily in reducing pain and improving quality of life. Those receiving either treatment experienced an overall improvement of greater than 80%, which is attributed to a reduction in pain, fatigue, headache, and gastrointestinal symptoms (92300).
• Gastrointestinal bleeding. It is unclear if spraying rhubarb powder with a gastroscope reduces gastrointestinal bleeding. Details: In patients with acute gastrointestinal bleeding, a meta-analysis of mainly preliminary clinical research shows that spraying rhubarb powder under a gastroscope has a small to moderate hemostatic effect over 24-72 hours when compared with norepinephrine. The risk of re-bleeding over 48 hours was also reduced by about 58% (103474).
• Herpes labialis (cold sores). Topical rhubarb has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that applying a cream containing rhubarb and sage to cold sores is similarly effective to acyclovir (Zovirax) cream. Acyclovir cream heals lesions in about 6.3 days; the rhubarb and sage cream heals lesions in about 7.2 days (10437). It is not clear if these improvements are due to the treatments used or to the natural resolution of the cold sores. Additionally, it is unclear if the benefit is due to rhubarb, other ingredients, or the combination.
• Hypercholesterolemia. It is unclear if oral rhubarb helps to lower cholesterol levels. Details: A very small clinical study including 10 males with hypercholesterolemia shows that eating ground rhubarb stalk fiber 27 grams daily for 4 weeks reduces total cholesterol by 8% and low-density lipoprotein (LDL) cholesterol by 9%, but does not affect high-density lipoprotein (HDL) cholesterol levels, when compared to baseline (71363). The validity of these findings is limited by the very small study size and the lack of a comparator group.
• Malignant pleural effusions. Topical rhubarb powder has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients living in China with advanced malignant cancer and malignant pleural effusions shows that applying a combination product (Hehuang Company) containing rhubarb powder 100 grams and mirabilite 400 grams to the chest wall for 8 hours daily for 28 days as an adjunct to standard therapy leads to partial or complete reduction of effusion in 67% of participants, compared with 55% of those receiving placebo and standard therapy (105961).
• Nasopharyngeal cancer. Oral rhubarb has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with nasopharyngeal carcinoma shows that taking a specific combination product (Shenlong) containing rhubarb and other herbs along with radiation therapy does not improve tumor remission or survival when compared to radiation therapy alone (71380).
• Nonalcoholic fatty liver disease (NAFLD). Oral rhubarb has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with NAFLD shows that taking 3-5 tablets of a specific Chinese herbal medicine (Danning Pian) containing rhubarb, giant knotweed, dried green orange peel, and dried ripe orange peel three times daily for 3 month improves lipids, liver function, and clinical symptoms (71315). It is not clear if this effect is due to rhubarb, the other ingredients, or the combination.
• Obesity. It is unclear if oral rhubarb is beneficial for weight loss. Details: A small clinical study in overweight and obese females shows that taking rhubarb with ginger, astragalus, red sage, and turmeric does not reduce body weight when compared with placebo (20346).
• Organophosphorus pesticide poisoning. It is unclear if giving rhubarb by gastric tube, nasal feeding, or enema is beneficial for organophosphorus pesticide poisoning. Details: A meta-analysis of low-quality clinical research in patients with acute organophosphorus pesticide poisoning shows that taking crude rhubarb 9-120 grams daily via gastric tube, nasal feeding, or retention enema, in conjunction with standard treatment, decreases the incidence of intermediate syndrome by 78% and organ dysfunction syndrome by 66% when compared to standard treatment alone. Rhubarb also reduces the duration of hospital stay by 2.8 days, but with no change in mortality rate, when compared to standard treatment alone. Standard treatment in these studies included atropine, pralidoxime, ventilation, diuresis, other supportive measures, and/or mannitol (92303).
• Sepsis. It is unclear if oral rhubarb is beneficial for sepsis. Details: A meta-analysis of low-quality clinical research in patients with sepsis or systemic inflammatory response syndrome (SIRS) shows that taking rhubarb powder in conjunction with conventional therapy reduces the incidence of gastrointestinal dysfunction, but does not reduce mortality rate, when compared to conventional therapy alone (92305).
• Stroke. Oral rhubarb has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of clinical research in patients with acute ischemic stroke shows that taking traditional Chinese medicine containing rhubarb root and rhizome in conjunction with traditional Western medicine for up to 30 days enhances overall clinical improvement by 27% when compared with traditional Western medicine alone. However, the validity of this outcome is limited by small sample size, the variability in the Chinese medicine formulas used, and the high risk for bias of the included studies (92299). More evidence is needed to rate rhubarb for these uses.

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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 the stalk is used in amounts commonly found in foods and when the root is used as a food flavoring. Rhubarb has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when the root or rhizome is used orally and appropriately in medicinal amounts for up to 2 years (92294,92295,92297). ...when the stalk is used orally and appropriately in medicinal amounts for up to 4 weeks (71351,71363,97920). ...when used topically and appropriately (10437,97919).

POSSIBLY UNSAFE ...when the leaf is used orally. Rhubarb leaf contains oxalic acid and soluble oxalate, which can cause abdominal pain, burning of the mouth and throat, diarrhea, nausea, vomiting, seizures, and death (17).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used in medicinal amounts, rhubarb root is a stimulant laxative; avoid using (12).

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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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CORTICOSTEROIDS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, frequent and high doses of rhubarb might increase the risk of hypokalemia when taken with corticosteroids.  Details Rhubarb has stimulant laxative effects. Overuse of rhubarb might compound corticosteroid-induced potassium loss (2,12).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking rhubarb with cyclosporine might reduce cyclosporine levels.  Details Animal research shows that co-administration of rhubarb decoction 0.25 or 1 gram/kg with cyclosporine 2.5 mg/kg, decreases cyclosporine maximum plasma concentration and overall exposure levels when compared with taking cyclosporine alone. The authors theorize that rhubarb might reduce cyclosporine bioavailability by inducing of P-glycoprotein and/or cytochrome P450 3A4 (92304). However, since rhubarb was administered as a single oral dose and enzyme induction usually occurs after multiple doses, it is possible that cyclosporine absorption was actually reduced via rhubarb's stimulant laxative effects (12). Also, the composition of the rhubarb decoction was not described.

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, overuse of rhubarb might increase the risk of adverse effects when taken with digoxin.  Details Rhubarb has stimulant laxative effects. Overuse of rhubarb might cause potassium depletion, increasing the risk of digoxin toxicity (12,19).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, frequent and high doses of rhubarb might increase the risk of hypokalemia.  Details Rhubarb has stimulant laxative effects. Overuse of rhubarb might cause potassium depletion and compound diuretic-induced potassium loss (12,19).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of rhubarb with potentially hepatotoxic drugs might increase the risk of developing liver damage.  Details Some animal research suggests that anthraquinones in rhubarb might have hepatotoxic effects (105960). Also, rhubarb use has been linked to at least 24 cases of liver injury, although details on the dose of rhubarb and duration of use in these cases is unclear (100963).

NEPHROTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, long-term use of anthraquinones from rhubarb might increase the risk of nephrotoxicity when used with nephrotoxic drugs.  Details The anthraquinone constituents of rhubarb have been shown to induce nephrotoxicity in animal research (71322). Additionally, in a case report, a 23-year old female presented with kidney failure after taking 6 tablets of a proprietary slimming agent (found to contain the anthraquinones emodin and aloe-emodin from rhubarb) daily for 6 weeks and then adding diclofenac 25 mg 4 times daily for 2 days. The authors postulate that the anthraquinone constituents of rhubarb contributed to the renal dysfunction, and the addition of diclofenac, a nephrotoxic drug, led to renal failure (15257). Until more is known, advise patients to avoid taking rhubarb if they are taking other potentially nephrotoxic drugs.

STIMULANT LAXATIVES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, rhubarb might increase the risk for fluid and electrolyte loss when taken with other stimulant laxatives.  Details Rhubarb has stimulant laxative effects (12). Concomitant use with stimulant laxatives might compound fluid and electrolyte loss (24427).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, excessive use of rhubarb might increase the risk of bleeding when taken with warfarin.  Details Rhubarb has stimulant laxative effects and can cause diarrhea (12,19). Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. Advise patients who take warfarin not to take excessive amounts of rhubarb.

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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, rhubarb root and stalk are well tolerated when used in food amounts and seem to be well tolerated when used in medicinal amounts. Rhubarb leaf contains oxalic acid and can be toxic. Topically, rhubarb seems to be well tolerated.
Most Common Adverse Effects:
Orally: Cramps, diarrhea, gastrointestinal discomfort, nausea, vomiting.
Topically: Rash.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.

Cardiovascular ...Orally, chronic use or abuse of rhubarb can cause arrhythmias (12).

Dermatologic ...Orally, rhubarb taken alone or in combination with other ingredients has been reported to cause rash (71315,71342). Topically, short term application of a specific product (Pyralvex) containing rhubarb, salicylic acid, and ethanol to the gums has been reported to cause slight burning and dark discoloration of the gums in approximately 1% of patients (71369). It is unclear if this effect is due to rhubarb, other ingredients, or the combination.

Endocrine ...Orally, chronic use or abuse of rhubarb can cause electrolyte loss (especially potassium), hyperaldosteronism, albuminuria, and edema (12).

Gastrointestinal ...Orally, rhubarb can cause cramp-like or spasmodic gastrointestinal discomfort, watery diarrhea, and uterine contractions (18). Rhubarb, alone or in combination with other ingredients, has also been reported to cause bloating, nausea, diarrhea, vomiting, and stomach upset or pain in clinical studies. Diarrhea is more common with a starting dose of at least 3 grams of extract (71315,71329,71339,71340,71341,71342,71373,92300). Chronic use or abuse of rhubarb can cause inhibition of gastric motility and pseudomelanosis coli (pigment spots in the intestinal mucosa) (12,6138).
Although some research suggests that rhubarb and other anthranoid laxatives might increase the risk of colorectal cancer due to pseudomelanosis coli (30743), more recent research suggests that this condition is harmless, typically reversed with rhubarb discontinuation, and not associated with an increased risk for colorectal adenoma or carcinoma (6138).

Hematologic ...Orally, chronic use or abuse of rhubarb can cause hematuria (12).

Hepatic ...Orally, chronic use of anthraquinone-containing products, such as rhubarb, has been associated with hepatotoxicity (15257). Use of rhubarb specifically has been linked to at least 24 reports of liver injury, although details on the dose of rhubarb and duration of use in these cases are not clear (100963). In one clinical study, rhubarb, taken in combination with other ingredients, has been reported to cause mild to moderate elevations of serum alanine aminotransferase (71315).

Immunologic ...Orally, rhubarb has rarely been reported to cause anaphylaxis (18).

Musculoskeletal ...Orally, chronic use or abuse of rhubarb can cause accelerated bone deterioration and muscular weakness (12).

Renal ...Orally, chronic use or abuse of rhubarb can cause electrolyte loss (especially potassium), albuminuria, hematuria, dehydration, and nephropathies (12). There is one case report of renal failure in a patient who took a product containing rhubarb for six weeks. The patient presented with renal failure two days after starting diclofenac, which is known to have nephrotoxic effects. It is hypothesized that the combination of diclofenac with the anthraquinone constituents of rhubarb precipitated renal dysfunction (15257).

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