Advanced Lipid Control by Life Extension

LIKELY EFFECTIVE

• Mental alertness. Consumption of black tea can improve or prevent declines in mental alertness, attention, and cognitive capacity. Details: Preliminary clinical research in healthy people shows that consumption of black tea containing caffeine 30-100 mg, as well as other caffeinated beverages, throughout the day prevents a decline in alertness and cognitive capacity when compared with placebo (4221,4224,92404). Also, some preliminary clinical research in healthy people shows black tea can improve attention. The effect may be dose-dependent, with greater effects observed in patients consuming black tea that contains higher concentrations of caffeine and theanine (92404). Caffeine can improve mental performance and alertness following prolonged sleep deprivation (10205). Combining caffeine with taurine seems to provide a small improvement in mental performance (9899). Combining caffeine with glucose as an "energy drink" seems to improve mental performance when compared with placebo or either caffeine or glucose alone (13732).

POSSIBLY EFFECTIVE

• Hypotension. Consumption of black tea seems to increase blood pressure in older patients with postprandial hypotension. Details: Several clinical studies in older adults with postprandial hypotension show that drinking caffeinated beverages such as black tea seems to increase blood pressure in the short-term when compared with placebo or not drinking caffeinated beverages (11834,11835).
• Myocardial infarction (MI). Consumption of black tea seems to be associated with a reduced risk of MI. Details: There is some evidence that people who consume at least one cup of black tea daily have a lower risk of MI when compared with not drinking tea (4222,8119,8121). Consuming black tea for at least one year before a heart attack also seems to be associated with a 28% to 44% reduced risk of subsequent death when compared with not drinking tea (8120).
• Osteoporosis. Consumption of black tea seems to have beneficial effects on bone health. Details: Population research suggests that consuming black tea is associated with increased bone mineral density, especially in older females aged 65-76 years and those whose habitual tea consumption extends beyond 10 years, when compared with not drinking tea (6404,8116). Black tea consumption also seems to be associated with a lower risk of hip fracture in adults aged 50 years or more (10949,15014).
• Ovarian cancer. Consumption of black tea seems to be associated with a reduced risk of ovarian cancer. Details: Adults who regularly consume tea, including black tea or green tea, appear to have a significantly lower risk of developing ovarian cancer when compared with those who never or seldom consume tea (9228,13208). In one prospective population study, adults who consume at least 2 cups of tea daily have a 46% lower risk of ovarian cancer when compared with those who do not regularly consume tea (13208).
• Parkinson disease. Consumption of black tea seems to be associated with a reduced risk of Parkinson disease.
• Parkinson disease. For males, the effects seem to be dose related. For example, males consuming 421-2716 mg of total caffeine (equivalent to 5-33 cups of black tea) from any source daily seem to have the greatest reduction in risk. However, there seems to be a significant reduction in risk even with consumption of as little as 124-208 mg of total caffeine (equivalent to 1-3 cups of black tea) daily (6022). In females, the effects do not seem to be dose related. Moderate consumption of caffeine (equivalent to 1-4 cups black tea daily) seems to provide the most reduction in risk (1238). Also, drinking tea appears to be associated with a reduced incidence of Parkinson disease among people who smoke when compared with almost never drinking tea (9236).

POSSIBLY INEFFECTIVE

• Bladder cancer. Consumption of black tea does not seem to be associated with a reduced risk of urinary tract cancers, including bladder cancer. Details: Observational research has found that drinking tea, including black and green tea, is not associated with a reduced risk of urinary tract cancers, including bladder cancer, when compared with those who almost never drink black tea (36482,36561).
• Breast cancer. Consumption of black tea does not seem to be associated with a reduced risk of breast cancer. Details: Observational research has found that drinking black tea is not associated with a lower risk of breast cancer when compared with not drinking black tea (9235,92406).
• Colorectal cancer. Consumption of black tea does not seem to be associated with a reduced risk of colorectal cancer. Details: Some population research has found that drinking tea, including black tea or green tea, might be associated with a reduced risk of colorectal cancer when compared with little or no tea consumption (9234,36535). However, most research has found that drinking tea is not associated with a reduced risk of colorectal cancer (9222,9223,9234,36385,36416,36474,36535,36553,36582). Additionally, some population research has found that increased consumption of black tea is associated with an increased risk of colorectal cancer when compared with those who almost never drink black tea (8041,36482).
• Diabetes. Consumption of black tea does not seem to be associated with a reduced risk of diabetes and does not seem to improve glycemic control in patients with diabetes. Details: Preliminary clinical research in patients with diabetes shows that taking an extract of black and green tea daily for 3 months does not reduce glycated hemoglobin (HbA1C) when compared with placebo (36434). Additionally, population research in Japanese adults has found that drinking at least 1 cup of black tea daily does not seem to be associated with a lower risk of developing type 2 diabetes when compared with drinking less than 1 cup daily (14313).
• Endometrial cancer. Consumption of black tea does not seem to be associated with a reduced risk of endometrial cancer. Details: A meta-analysis of results from population research has found that increasing black tea intake by 1 cup per day is not associated with a reduced risk of endometrial cancer when compare with no or low black tea consumption (92409).
• Esophageal cancer. Consumption of black tea does not seem to be associated with a reduced risk of esophageal cancer. Details: A meta-analysis of results from population research has found that people who drink higher amounts of black tea do not have a reduced risk of esophageal cancer when compared with those who drink lesser amounts (90186). However, some population research has found that drinking large amounts of strong black tea is associated with a two-fold INCREASED risk for esophageal cancer when compared with people who drink less black tea (102756).
• Gastric cancer. Consumption of black tea does not seem to be associated with a reduced risk of gastric cancer. Details: While some epidemiological evidence has found that increased consumption of tea, including black or green tea, is associated with a reduced risk of stomach cancer (36561), most evidence shows that drinking tea is not associated with a reduced stomach cancer risk (9222,9223,36553,36333). Additionally, some epidemiological evidence has found that consumption of tea may be associated with an increased risk of mortality due to stomach cancer when compared with nonregular tea consumption (36474).
• Lung cancer. Consumption of black tea does not seem to be associated with a reduced risk of lung cancer. Details: Most population research found that drinking up to 5 cups of black tea daily is not associated with reduced risk of lung cancer (36474,36553,90177,97128). One population study even found an increase in risk of lung cancer associated with tea consumption, including black and green tea, when compared with nonregular tea consumption. However, this study did not adjust for the patients' baseline smoking status and carcinogen exposure (36474).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atherosclerosis. Consumption of black tea seems to be associated with a reduced risk of severe, but not mild or moderate, aortic atherosclerosis. Details: Epidemiological research has found that increased intake of brewed black tea (125-500 mL or 1-4 cups) is associated with a reduced risk of severe aortic atherosclerosis, especially in females. However, black tea intake is not associated with a reduced risk of mild or moderate aortic atherosclerosis (3450).
• Cardiovascular disease (CVD). Consumption of black tea may be associated with a modest reduction in CVD-related mortality. Details: A prospective cohort study of nearly 500,000 adults 40-69 years of age in the United Kingdom Biobank shows that black tea intake in quantities greater than 1 cup daily is associated with a modestly reduced rate of CVD-related mortality over a mean follow-up of about 11 years. Consuming anywhere between 2-9 cups of black tea daily resulted in similar hazard ratios; consuming 10 or more cups per day may be associated with a further reduction in risk (108970).
• Chronic obstructive pulmonary disease (COPD). It is unclear if black tea is associated with a reduced risk of COPD. Details: One prospective, observational study in older adults has found that consumption of at least 3 cups daily of tea, including black tea, oolong tea, and green tea, is associated with a 23% reduced risk of COPD prevalence and a 65% reduced risk of developing COPD in models adjusted for potential confounders when compared with the lowest tea consumption (107201).
• Coronary heart disease (CHD). It is unclear if black tea is associated with a reduced risk of CHD or CHD-related mortality. Details: Although a meta-analysis of population research found that general tea consumption might protect against cardiovascular disease (CVD) or death from CVD, a sub-group analysis has found that drinking black tea does not seem to offer protection (102728). In fact, some individual population research found that black tea consumption is associated with an increased incidence of CHD progression and CHD mortality in those with existing CHD (220,36339). In contrast, observational research in healthy adults has found that those who drink black tea regularly have a decreased risk of developing CHD (7726,36363,36391,36420).
• Dementia. It is unclear if black tea, consumed in conjunction with coffee, is associated with a reduced risk of dementia. Details: A prospective, observational study suggests consumption of tea, including black tea, of at least 4 cups with 0.5-1 cups of coffee daily is associated with a 30% reduced risk of dementia when compared with not drinking tea or coffee. Also, drinking 2-3 cups daily of both tea and coffee is associated with a 28% reduced risk of dementia stroke when compared with not drinking tea and coffee (107204).
• Depression. It is unclear if black tea is associated with a reduced risk of depression. Details: Observational research in healthy adult office workers without a history of anxiety or depression has found that consumption of at least 1-4 cups daily of black tea, as well as caffeine from other sources, is associated with a 41% to 61% reduced risk of depression scores in multiple models adjusted for potential confounders (107202).
• Diarrhea. Black tea seems to improve stool consistency in children with acute nonbacterial diarrhea. Details: Preliminary clinical research in children with acute nonbacterial diarrhea shows that taking a one-time dose of black tea 500-1000 mg as tablets dissolved in water improves stool consistency after 24 hours when compared with placebo (97126).
• Halitosis. It is unclear if black tea is beneficial in patients with halitosis. Details: A very small study in healthy adults shows that rinsing with 10 mL of black tea for 30 seconds following L-cysteine-induced halitosis improves the concentration of volatile sulfur compounds in breath samples when compared with baseline. These concentrations also were improved at 2 hours, but not at 1 hour, when compared with control. It is unclear if the improvement from baseline differed between groups (107203).
• Headache. Although there has been interest in consuming black tea for headache, there is insufficient reliable information about the clinical effects of black tea for this purpose.
• Hyperlipidemia. The evidence for the benefits of black tea in reducing cholesterol is conflicting. Details: One small clinical study in mildly hypercholesterolemic adults shows that drinking black tea reduces total cholesterol and low-density lipoprotein (LDL) cholesterol levels (36401). However, other studies have found that drinking black tea or taking black tea extract does not reduce cholesterol or triglyceride levels in healthy people or in those with cardiovascular risk factors (36376,36436,36581,36592). Meta-analyses of clinical research also report conflicting findings. Several meta-analyses in healthy people and in patients with coronary artery disease or hypercholesterolemia suggest that drinking black tea or taking black tea extract does not reduce total cholesterol or LDL cholesterol levels when compared with placebo (92407,102738). However, several other small meta-analyses of clinical studies in healthy people or those at risk for cardiovascular disease show that drinking black tea 3-5 servings daily or taking black tea extract 1-6 grams daily for up to 6 months modestly reduces LDL cholesterol levels when compared with placebo (90146,92408). Reasons for the conflicting findings are not entirely clear. One analysis suggests that black tea has a greater effect on LDL cholesterol in patients with higher cardiovascular risks than those who are healthy (92408). The effect of black tea on cholesterol levels does not appear to be influenced by the duration of treatment or the type of black tea used (tea leaf vs. tea extract) (92407,92408).
• Hypertension. Consumption of black tea seems to modestly reduce blood pressure, although any effect may not be considered clinically significant. Details: Most epidemiological research and some meta-analyses of clinical research show that consumption of 3-5 cups of black tea daily or black tea extracts 6 grams daily for up to 6 months can modestly reduce blood pressure, although any benefits are not likely to be considered clinically significant (36400,90146,92405,104582,104583). One meta-analysis of clinical research in a mixed population with normotension, hypertension, coronary artery disease, mild hypercholesterolemia, or at high risk of cardiovascular disease shows that taking black tea 300-1800 mL daily for 7 days to 6 months reduces systolic blood pressure by about 1.5 mmHg and diastolic blood pressure by about 0.8 mmHg when compared with control (104582). Other analyses show similar reductions of up to 2 mmHg (90146,92405). However, the effect in patients with hypertension is unclear because this population is rarely analyzed separately. In a meta-analysis of three clinical trials limited to patients with hypertension, and excluding studies related to purified black tea extracts or isolated components, there was no statistically significant effect on blood pressure when compared with control (104583). Interestingly, most of the individual clinical studies in these analyses did NOT find a reduction in blood pressure from black tea consumption (104582). This might be because most of these studies had a short duration (1452,36376,36581,104583) or were underpowered to detect a modest effect (36436). Furthermore, these studies did not use out-of-office blood pressure monitoring, such as 24-hour ambulatory blood pressure monitoring (ABPM). A robust clinical study using ABPM in patients with normotension and hypertension shows that drinking 3 cups of black tea (1493 mg powdered black tea solids containing 429 mg of polyphenols) daily for 6 months results in about 2 mmHg reduction in both systolic and diastolic blood pressure when compared with placebo (97127).
• Kidney stones (nephrolithiasis). Consumption of black tea seems to reduce the risk of developing kidney stones. Details: Population research has found that consuming one 8 oz cup of tea, such as black tea, daily is associated with an 8% decreased risk of developing kidney stones in females (4216).
• Oral cancer. Although there has been interest in consuming black tea for oral cancer, there is insufficient reliable information about the clinical effects of black tea for this purpose.
• Overall mortality. Consuming black tea may be associated with a modest reduction in overall mortality. Details: A prospective cohort study of nearly 500,000 adults between 40-69 years of age in the United Kingdom Biobank shows that consuming black tea in quantities greater than 1 cup daily is associated with a modestly reduced all-cause mortality over a mean follow-up of about 11 years. Increasing consumption beyond 2-3 cups per day does not further reduce overall mortality rate (108970).
• Pancreatic cancer. It is unclear if consumption of black tea is associated with a reduced risk of pancreatic cancer. Details: One prospective, observational study has found that Japanese males who drink more than 1 cup of black tea daily are not at a lower risk of developing pancreatic cancer when compared with those who almost never drink black tea (36482). However, another observational study in Polish males has found that increased tea consumption over a lifetime is associated with a reduced risk of pancreatic cancer (36550).
• Prostate cancer. It is unclear if consumption of black tea is beneficial for reducing the risk of prostate cancer. Details: Observational research has found that black tea consumption is associated with a reduced risk of prostate cancer when compared with those who almost never drink black tea (36482).
• Renal cell carcinoma. It is unclear if consumption of black tea is beneficial for reducing the risk of kidney cancer. Details: Prospective, observational research in males has found that drinking higher amounts of tea, including black and green tea, is associated with an increased risk of kidney cancer when compared with nonregular tea consumption (36474).
• Stress. It is unclear if consumption of black tea is beneficial for reducing stress. Details: Preliminary clinical research in healthy, nonsmoking males shows that drinking black tea daily for 6 weeks does not improve blood pressure, heart rate, or subjective stress ratings in response to stressful tasks when compared with placebo (36426).
• Stroke. It is unclear if consumption of black tea is associated with a reduced risk of stroke or death from stroke. Details: Several prospective, observational studies have found that higher intake of tea, including black tea, is associated with a decreased incidence of stroke when compared with lower intake (7716,107204), as well as a modestly reduced risk of stroke-related mortality (108970). Consumption of at least 2 cups daily of tea, including black tea, is associated with a 16% reduced risk of stroke when compared with drinking no tea. Drinking 2-3 cups daily of both tea and coffee is associated with a 38% reduced risk of stroke when compared with not drinking either of these beverages. The combination of 0.5-1 cups of coffee and 2-3 cups of tea daily, but not tea alone, also is associated with a 50% reduced risk of post-stroke dementia when compared with not drinking tea and coffee (107204). More evidence is needed to rate black tea 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.

(Read more about INDIAN GOOSEBERRY)

LIKELY SAFE ...when consumed orally in moderate amounts (1452,9222,9223,9224,9228,9233,9234,9235,9236,36376)(36426,36434,36436,36581). Black tea contains caffeine. According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, drinking up to 4 cups of black tea daily, or approximately 400 mg of caffeine, is not associated with significant adverse cardiovascular, bone, behavioral, or reproductive effects in healthy adults (11733,98806). The US Dietary Guidelines Advisory Committee states that there is strong and consistent evidence that consumption of caffeine 400 mg daily is not associated with increased risk of major chronic diseases, such as cardiovascular disease or cancer, in healthy adults (98806).

POSSIBLY UNSAFE ...when consumed orally long term or in high amounts. Black tea contains a significant amount of caffeine. Chronic use, especially in large amounts, can produce tolerance, habituation, psychological dependence, and other significant adverse effects. Doses of caffeine greater than 600 mg per day, or approximately 6 cups of black tea, have been associated with significant adverse effects such as tachyarrhythmias and sleep disturbances (11832). These effects would not be expected to occur with the consumption of decaffeinated black tea. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as black tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.

LIKELY UNSAFE ...when consumed orally in very high amounts. The fatal acute oral dose of caffeine is estimated to be 10-14 grams (150-200 mg per kilogram). Serious toxicity can occur at lower doses depending on variables in caffeine sensitivity such as smoking, age, prior caffeine use, etc. (11832).

CHILDREN: POSSIBLY SAFE
when used in food and beverage amounts (4912,11833).

PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts. Due to the caffeine content of black tea, mothers should closely monitor their intake to ensure moderate consumption. Caffeine crosses the human placenta but is not considered a teratogen. Fetal blood concentrations of caffeine approximate maternal concentrations (4260). The use of caffeine during pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects (2708,2709,2710,2711,9606,11733,16014,16015,37802,37584). In some studies, consuming amounts over 200 mg daily is associated with a significantly increased risk of miscarriage (16014). This increased risk may be most likely to occur in females with genotypes that confer a slow rate of caffeine metabolism (98806). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, most healthy patients can safely consume doses up to 300 mg daily during pregnancy without an increased risk of spontaneous abortion, stillbirth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). Advise keeping caffeine consumption below 300 mg daily. This is similar to the amount of caffeine in about 3 cups of black tea. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as black tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.

PREGNANCY: POSSIBLY UNSAFE
when used orally in large amounts. Caffeine from black tea crosses the placenta, producing fetal blood concentrations similar to maternal levels (4260). Consumption of caffeine in amounts over 300 mg daily is associated with a significantly increased risk of miscarriage (16014,98806). Advise keeping caffeine consumption from all sources below 300 mg daily. This is similar to the amount of caffeine in about 3 cups of black tea. High doses of caffeine throughout pregnancy have resulted in symptoms of caffeine withdrawal in newborn infants (9891). High doses of caffeine have also been associated with spontaneous abortion, premature delivery, and low birth weight (2709,2711,24995,24998,37561,37898,38012,38186,38199,38212)(38285,38290). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as black tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. Preliminary evidence from a population study also suggests that increasing consumption of black tea might increase the risk of spina bifida (15112); however, this finding needs to be verified with additional research. More evidence is needed to determine the safety of using black tea during pregnancy. For now, advise avoidance of large quantities of black tea during pregnancy.

LACTATION: POSSIBLY SAFE
when used orally in moderate amounts. Due to the caffeine content of black tea, caffeine intake should be closely monitored. Breast milk concentrations of caffeine are thought to be approximately 50% of maternal serum concentrations. Minimal consumption would likely result in limited exposure to a nursing infant (9892).

LACTATION: POSSIBLY UNSAFE
when used orally in large amounts. Consumption of black tea might cause irritability and increased bowel activity in nursing infants (6026). Black tea might also interfere with iron metabolism and folic acid bioavailability in nursing infants (631,53782). Large doses or excessive intake of black tea should be avoided during lactation.

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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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ADENOSINE (Adenocard) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, black tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.  Details Black tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level (38172). However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products, be stopped 24 hours prior to pharmacological stress tests (11770). However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).

ALCOHOL (Ethanol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, alcohol might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Concomitant use of alcohol and caffeine can increase caffeine serum concentrations and the risk of caffeine adverse effects. Alcohol reduces caffeine metabolism (6370,24693).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, black tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Black tea contains caffeine. Caffeine is reported to have antiplatelet activity (8028,8029,36425). Theoretically, the caffeine in black tea might increase the risk of bleeding when used concomitantly with antiplatelet drugs. However, this interaction has not been reported in humans.

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, taking black tea with antidiabetes drugs might interfere with blood glucose control.  Details Black tea contains caffeine. Reports claim that caffeine might increase or decrease blood sugar levels (6024,8646). Also, some evidence in healthy individuals suggests that drinking black tea reduces blood sugar (92403).

BETA-ADRENERGIC AGONISTS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of large amounts of black tea might increase cardiac inotropic effects of beta-agonists.  Details Black tea contains caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists (15).

CARBAMAZEPINE (Tegretol) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, black tea might reduce the effects of carbamazepine and increase the risk for convulsion.  Details Black tea contains caffeine. Animal research suggests that caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg (23559,23561). Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals (23562).

CIMETIDINE (Tagamet) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = B Theoretically, concomitant use might increase the effects and adverse effects of caffeine in black tea.  Details Black tea contains caffeine. Cimetidine can reduces caffeine clearance by 31% to 42% (11736,24700).

CLOZAPINE (Clozaril) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, black tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.  Details Concomitant administration of black tea and clozapine might theoretically cause acute exacerbation of psychotic symptoms due to the caffeine in black tea. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine (13741).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in black tea.  Details Black tea contains caffeine. Oral contraceptive drugs can decrease caffeine clearance by 40% to 65% (2714,11737).

CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Caffeine is metabolized by CYP1A2 (3941,5051,11741,23557,23573,23580,24958,24959,24960,24962), (24964,24965,24967,24968,24969,24971,38081,48603). Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from black tea and increase caffeine levels.

DIPYRIDAMOLE (Persantine) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, black tea might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.  Details Black tea contains caffeine. Caffeine is a methylxanthine that may inhibit dipyridamole-induced vasodilation (11770,11772,24974,37985,53795). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products such as black tea, be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).

DISULFIRAM (Antabuse) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, disulfiram might increase the risk of adverse effects from caffeine.  Details Black tea contains caffeine. In human research, disulfiram decreases the clearance and increases the half-life of caffeine (11840).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, using black tea with diuretic drugs might increase the risk of hypokalemia.  Details Black tea contains caffeine. Caffeine, especially in excessive amounts, can reduce potassium levels due to stimulation of the sodium-potassium pump (23579,37905,37953,38003,38034). Diuretics can also cause lower potassium levels.

EPHEDRINE Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use might increase the risk for simulant adverse effects.  Details Black tea contains caffeine. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death (6486,9740,10307). Tell patients to avoid taking caffeine with ephedrine and other stimulants.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, estrogens might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Estrogen inhibits caffeine metabolism (2714).

ETHOSUXIMIDE (Zarontin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black tea might reduce the effects of ethosuximide and increase the risk for convulsions.  Details Black tea contains caffeine. Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide (23560). However, this effect has not been observed in humans.

FELBAMATE (Felbatol) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black tea might reduce the effects of felbamate and increase the risk for convulsions.  Details Black tea contains caffeine. Animal research suggests that a high dose of caffeine 161.7 mg/kg can decrease the anticonvulsant activity of felbamate (23563). However, this effect has not been observed in humans.

FLUCONAZOLE (Diflucan) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, fluconazole might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022,24978).

FLURBIPROFEN (Ansaid, others) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, black tea might decrease the metabolism of flurbiprofen.  Details In vitro research shows that black tea decreases the metabolism of flurbiprofen, a cytochrome P450 2C9 (CYP2C9) substrate, by about 10%. However, clinical research suggests that drinking black tea does not significantly affect flurbiprofen plasma levels, metabolism, or elimination (11094).

FLUTAMIDE (Eulexin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black tea might increase the levels and adverse effects of flutamide.  Details Black tea contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553). Theoretically, concomitant use of caffeine and flutamide might increase serum concentrations of flutamide and increase the risk of adverse effects.

FLUVOXAMINE (Luvox) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Fluvoxamine reduces caffeine metabolism (6370,38287).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, abrupt black tea withdrawal might increase the levels and adverse effects of lithium.  Details Black tea contains caffeine. Abrupt caffeine withdrawal can increase serum lithium levels (609). Two cases of lithium tremor that worsened with abrupt coffee withdrawal have been reported (610).

Metformin (Glucophage) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, metformin might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Animal research suggests that metformin can reduce caffeine metabolism (23571). Theoretically, concomitant use can increase caffeine serum concentrations and the risk of caffeine adverse effects.

METHOXSALEN (Oxsoralen) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Methoxsalen can reduce caffeine metabolism (23572). Concomitant use can increase caffeine serum concentrations and the risk of caffeine adverse effects.

MEXILETINE (Mexitil) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, mexiletine might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Mexiletine can decrease caffeine elimination by 50% (1260,11741,24981).

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk of a hypertensive crisis.  Details Black tea contains caffeine. Caffeine has been shown to inhibit monoamine oxidase (MAO) A and B in laboratory studies (37724,37877,37912,38108). Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15). In a case report, a patient that consumed 10-12 cups of caffeinate coffee and took the MAOI tranylcypromine presented with severe hypertension (91086). Hypertension was resolved after the patients switched to drinking decaffeinated coffee.

NICOTINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, concomitant use might increase the risk of hypertension.  Details Black tea contains caffeine. Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly (36549).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black tea might reduce the absorption of organic anion-transporting polypeptide (OATP) substrates.  Details In vitro, black tea extract inhibits organic anion-transporting polypeptide (OATP)2B1. OATP2B1 is expressed in the small intestine and liver and is responsible for the uptake of drugs and other compounds. In an animal model, black tea extract was found to inhibit the absorption of rosuvastatin, a substrate of OATP2B1 (104584). However, this effect has not been reported in humans.

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, black tea might decrease the effects of pentobarbital.  Details Black tea contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).

PHENOBARBITAL (Luminal) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, black tea might reduce the effects of phenobarbital and increase the risk for convulsions.  Details Black tea contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital (23558,23559,23561). The exact mechanism of this interaction is unclear.

PHENOTHIAZINES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, phenothiazines might increase the levels and adverse effects of caffeine. Also, black tea may bind to phenothiazines and reduce their absorption.  Details Black tea contains caffeine. Phenothiazines can reduce the metabolism of caffeine by inhibiting cytochrome P450 1A2 (CYP1A2) (23573,23574). Additionally, the tannins in black tea may bind to phenothiazines in the gastrointestinal tract and reduce their absorption (626,627).

PHENYLPROPANOLAMINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure (11738). Phenylpropanolamine also seems to increase caffeine serum levels (13743).

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black tea might reduce the effects of phenytoin and increase the risk for convulsions.  Details Black tea contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenytoin (23559,23561). The effect does not seem to be related to the seizure threshold-lowering effects of caffeine. However, the exact mechanism of this interaction is unclear.

PIOGLITAZONE (Actos) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black tea might increase the levels and clinical effects of pioglitazone.  Details Black tea contains caffeine. Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This could increase the antidiabetic effects of pioglitazone (108812). However, the exact mechanism of this interaction is unclear.

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Concomitant use of caffeine and quinolones can decrease caffeine clearance and increase effects and risk of adverse effects (606,607,608,23555,24695,24696,24697).

RILUZOLE (Rilutek) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.  Details Black tea contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce metabolism of one or both agents (11739).

ROSUVASTATIN (Crestor) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might decrease the levels and clinical effects of rosuvastatin.  Details In animals, taking black tea extract along with rosuvastatin reduces plasma levels of rosuvastatin by approximately 48%. In vitro, black tea extract was found to inhibit organic anion-transporting polypeptide (OATP)2B1, a protein expressed in the small intestine that is responsible for the uptake of rosuvastatin and other compounds (104584). This effect has not been reported in humans.

STIMULANT DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, concomitant use might increase stimulant adverse effects.  Details Black tea contains caffeine. Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects (11832).

TERBINAFINE (Lamisil) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, terbinafine might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).

THEOPHYLLINE Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, black tea might increase the levels and adverse effects of theophylline.  Details Black tea contains caffeine, which can increase theophylline levels (11862,24984).

TIAGABINE (Gabitril) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, black tea might increase the levels and adverse effects of tiagabine.  Details Black tea contains caffeine. Animal research suggests that chronic caffeine administration can increase the serum concentrations of tiagabine. However, concomitant use does not seem to reduce the antiepileptic effects of tiagabine (23561).

TICLOPIDINE (Ticlid) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.

TRICYCLIC ANTIDEPRESSANTS (TCAs) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, TCAs might bind with black tea constituents when taken at the same time.  Details In vitro research suggests that the tannins in black tea might cause precipitation of TCAs (626,627). However, this effect has not been reported in humans.

VALPROATE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black tea might reduce the effects of valproate and increase the risk for convulsions.  Details Black tea contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of valproate (23558,23559,23561). However, the exact mechanism of this interaction is unclear.

VERAPAMIL (Calan, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the levels and adverse effects of caffeine.  Details Black tea contains caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Consuming large amounts of black tea might decrease the effects of warfarin.  Details In one case, a 67-year-old female who took warfarin and who regularly consumed large amounts of black tea had a stable international normalized ratio (INR) of 1.7 to 2.7. However, the INR increased to 5 when tea consumption was discontinued. It is thought that the vitamin K content of black tea may have reduced the effects of warfarin (16902). Monitor patients carefully who start or discontinue drinking black tea while taking warfarin.

(Read more about BLACK TEA)

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).

(Read more about INDIAN GOOSEBERRY)

General ...Orally, black tea is well tolerated when consumed as a beverage in moderate amounts.
Most Common Adverse Effects:
Orally: Many of the adverse effects of black tea can be attributed to its caffeine content, such as diuresis, gastric irritation, insomnia, nausea, nervousness, restlessness, tachycardia, tachypnea, tremors, and vomiting.
Serious Adverse Effects (Rare):
Orally: Many of the adverse effects of black tea can be attributed to its caffeine content, such as arrhythmia, chest pain, convulsions, delirium, premature heartbeat, and respiratory alkalosis. Large doses of caffeine can cause massive catecholamine release and subsequent sinus tachycardia, metabolic acidosis, hyperglycemia, and ketosis.

Cardiovascular ...Orally, black tea can cause some cardiovascular-related adverse events. Some of these effects may be due to the caffeine content of black tea. Acute administration of black tea can cause increased blood pressure. However, regular consumption does not seem to increase blood pressure or pulse, even in patients with mild hypertension (1451,1452,2722). Also, epidemiological research suggests that there is no association of caffeine consumption with incidence of hypertension (13739).
Black tea, which contains caffeine, may cause other adverse cardiovascular effects when used orally. These effects include tachycardia, tachypnea, chest pain, premature heartbeat, arrhythmia, and hypertension (2729,11832,11838,13735). Large doses of caffeine can also cause massive catecholamine release and subsequent sinus tachycardia (13734).
There is evidence that daily consumption of strong black tea (2 liters) or black tea solids (4 grams) can raise plasma homocysteine levels. It is unclear if lower doses have this effect (8035). Some epidemiological research has linked tea consumption with ischemic heart disease and total mortality (220,36339). Combining caffeinated beverages such as black tea with ephedra may theoretically increase the risk of adverse cardiovascular events. There is a report of ischemic stroke in an athlete who consumed ephedra 40-60 mg, creatine monohydrate 6 grams, caffeine 400-600 mg, and a variety of other supplements daily for 6 weeks (1275).

Dental ...Orally, black tea may cause tooth surface loss and teeth staining (36370).

Endocrine ...Black tea contains caffeine. Large doses of caffeine can cause massive catecholamine release and subsequent metabolic acidosis, hyperglycemia, and ketosis (13734).
Some evidence shows caffeine is associated with fibrocystic breast disease, breast cancer, and endometriosis. However, other research has not supported this finding (8043). Restricting caffeine in females with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996). A population analysis of the Women's Health Initiative observational study found no association between consumption of caffeine-containing beverages such as black tea and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors (108806). Also, a dose-response analysis of two low-quality observational studies found that high consumption of caffeine is not associated with an increased risk of breast cancer (108807).

Gastrointestinal ...Orally, caffeine in black tea can cause gastric irritation, nausea, and vomiting (11832,11838,13735). Some believe that long-term use of caffeine can cause withdrawal symptoms following discontinuation of use. However, the existence of caffeine withdrawal is controversial. Some researchers think that if it exists, it appears to be of little clinical significance (11839). Gastrointestinal withdrawal symptoms such as nausea and vomiting have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects. Clinically significant gastrointestinal symptoms caused by caffeine withdrawal may be uncommon (2723,11839).

Hematologic ...Orally, caffeine in black tea can cause hypokalemia (11832,11838,13735). In infants, black tea can cause microcytic anemia (631).

Immunologic ...Orally, caffeine in black tea can cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).

Musculoskeletal ...Some epidemiological research suggests that caffeine, which is found in black tea, may be associated with an increased risk of osteoporosis, but conflicting evidence exists. Caffeine can increase urinary excretion of calcium (2669,10202,11317). Females identified with a genetic variant of the vitamin D receptor appear to be at an increased risk for the detrimental effect of caffeine on bone mass (2669). However, moderate caffeine intake, less than 300 mg per day, does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317).
Some researchers believe that stopping regular use of caffeine may cause withdrawal symptoms such as muscle tension and muscle pains. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839).

Neurologic/CNS ...Orally, caffeine in black tea can cause insomnia, nervousness, headache, anxiety, agitation, jitteriness, restlessness, ringing in the ears, tremors, delirium, and convulsions (11832,11838,13735). Caffeine may also exacerbate sleep disturbances in patients with acquired immunodeficiency syndrome (AIDS) (10204).
There is some concern that stopping regular use of caffeine may cause withdrawal symptoms such as headache; tiredness and fatigue; decreased energy, alertness, and attentiveness; drowsiness; decreased contentedness; depressed mood; difficulty concentrating; irritability; and lack of clear-headedness are typical of caffeine withdrawal (13738). Other symptoms such as delirium, nervousness, restlessness, and anxiety have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839).

Oncologic ...There is some evidence that consumption of black tea (greater than 1 cup per day) may increase the risk of colon and rectal cancers (8041,36482). Drinking 3 or more cups daily has been shown to increase the risk of pancreatic cancer (36507). In addition, drinking black tea more than once a day, drinking strong black tea, or using more than 300 grams of tea leaves per month is associated with an approximately 2-fold increased risk of esophageal cancer when compared with drinking black tea up to once daily, drinking mild to moderate black tea, or using up to 300 grams of tea leaves per month (102756). Some evidence also shows caffeine, which is found in black tea, is associated with breast cancer in females. However, this is controversial since findings are conflicting (8043).

Pulmonary/Respiratory ...Orally, caffeine in black tea may cause tachypnea-induced respiratory alkalosis (11832,11838,13735). Some researchers think that stopping regular use of caffeine may cause withdrawal symptoms such as runny nose. However, this symptom may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839).

Renal ...Orally, caffeine in black tea may cause diuresis (11832,11838,13735).

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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).

(Read more about INDIAN GOOSEBERRY)