Cran-Plus by Indiana Botanic Gardens

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

(Read more about BUCHU)

POSSIBLY EFFECTIVE

• Urinary tract infections (UTIs). Cranberry products may possibly reduce the risk of repeat, symptomatic UTI in females with recurrent UTI, in children, and in people susceptible to UTI following kidney transplant, urogenital surgery, or radiation therapy near the urogenital system. While some positive evidence exists, most research suggests that cranberry products do not seem to reduce the risk of UTI in older adults in institutions, pregnant patients, or adults with neuromuscular dysfunction of the bladder. Cranberry is not recommended for the treatment of UTI in any population. Details: Cranberry appears to reduce the risk of UTI in some populations but not others. In healthy females at an increased risk of UTI or history of recurrent UTI, meta-analyses of clinical trials show that cranberry products decrease the overall risk of recurrent or first-time UTI by 26% to 35% (46473,92578,96739,111407). In 2019, the American Urological Association published guidelines stating that, based on low certainty evidence, clinicians may offer cranberry tablets or juice as prophylaxis for females with recurrent UTIs. Due to a lack of compelling evidence for any specific product, the guidelines recommend choosing formulations based on availability and tolerability (100855). In 2020, the US Food and Drug Administration (FDA) approved qualified health claims stating that consuming cranberry juice in doses of at least 8 ounces daily, or cranberry supplements in doses of at least 500 mg daily, may help reduce the risk of recurrent UTI in healthy females. However, the FDA has concluded that there is limited scientific evidence to support these claims (103302). The benefits of cranberry for prevention of UTI during pregnancy are unclear. Subgroup analysis of meta-analyses suggest that cranberry supplementation does not reduce the risk of UTI in pregnant adults compared with placebo or no treatment (100855,111407). A preliminary clinical study shows that drinking cranberry juice 240 mL three times daily until delivery does not reduce the frequency of asymptomatic bacteriuria or symptomatic UTI during pregnancy, although the study was not adequately powered to detect a difference in these outcomes (16415). In contrast, one preliminary clinical trial shows that UTI frequency was reduced in 70.5% of those ingesting cranberry juice 250 mL four times daily, compared with only 32% of those taking placebo (93670). In children, a meta-analysis shows that taking cranberry products probably reduces the risk of subsequent symptomatic UTIs by up to 54% compared with placebo or no treatment, but does not specify a particular formulation (111407). Clinical trials show that daily consumption of cranberry syrup (Pharmatoka), cranberry juice (Cranberry UR-50, Kikkoman Company) 100 mL, cranberry-lingonberry juice 50 mL, and cranberry extract (Anthocran) 120 mg reduce the risk of UTI recurrence in children (46452,96733,96737,108055). In contrast, another clinical trial shows that drinking cranberry juice (Ocean Spray Cranberries, Inc) 5 mL/kg daily for 6 months does not reduce the incidence of recurrent UTI when compared with placebo, although it does decrease the total number of UTI episodes and length of antimicrobial therapy per child (46470). In older, institutionalized adults, a meta-analysis of 5 studies evaluating the effectiveness of cranberry products shows little or no benefit in preventing symptomatic, culture-verified UTIs (111407). A clinical study in females residing in long-term care (LTC) facilities shows that taking a specific cranberry supplement (Ellura, Pharmatoka) once daily for 1 year does not reduce the incidence of UTI or asymptomatic bacteriuria (92517). However, clinical trials of cranberry products in elderly patients in LTC facilities suggest that cranberry may be more effective in patients at a higher risk for UTIs, such as those with diabetes, long-term catheterization, or recurrent UTIs (90041,108055), and in patients with E. coli-related UTIs (46389,46472). In one small study, providing all patients living in a LTC facility with 4 ounces of cranberry juice or six tablets of a specific concentrated cranberry product (Azo-Cranberry, i-Health, Inc.) daily for 13 months decreased the facility's overall monthly UTI rate from 27.7 to 20.7 (46492). In another clinical trial, taking cranberry juice cocktail (Ocean Spray Cranberries, Inc) 300 mL daily for 6 months decreased the rate of asymptomatic bacteriuria plus pyuria by 13% in older females living in institutional settings (7008). In another clinical trial, taking a cranberry capsule 500 mg, standardized to 1.8% PACs, twice daily for 12 months decreased the risk of UTI by around 26% in patients at high-risk for UTI, including those with catheters, diabetes, or at least one UTI in the previous 12 months (90041). Meta-analyses and clinical research show that cranberry products do not reduce the risk of UTI associated with neurogenic bladder, neuromuscular dysfunction, or insufficient bladder emptying in adults or children (2811,6759,11980,46379,46425,46473,90044,92578,96737,108055,111407). However, one study found benefit in patients with neurogenic bladder due to spinal cord injury taking cranberry capsules (Cran-Max, Proprietary Nutritionals, Inc.) 500 mg daily (46443). Cranberry products have also been evaluated in a variety of other high-risk populations, with mixed results. A meta-analysis of 7 studies shows that cranberry products reduce the risk of UTIs in people with increased susceptibility to UTI due to an intervention (e.g., kidney transplant, radiotherapy to urogenital system, or urogenital surgery) when compared with placebo (111407). Cranberry extracts do not seem to reduce the risk of UTIs in individuals undergoing hysterectomy and/or anterior vaginal repair (46465), pelvic floor surgery (104245), or in patients with multiple sclerosis (46496,111407). Taking cranberry powder capsules (NurtiCran90, Petefa AB) 550 mg three times daily for 5 days does not reduce the UTI rate at days 5 or 14 when compared with placebo in postoperative females with hip fracture receiving a urinary catheter; however, the study was not adequately powered to detect a difference in this outcome (96734). Other preliminary clinical research in elderly males with benign prostatic hyperplasia and a recent UTI shows that taking a standardized cranberry extract (Anthocran) 120 mg daily for 60 days reduces the UTI recurrence rate by about 62% when compared with placebo (96735). Cranberry supplements have been studied in a variety of formulations, but it is unclear whether certain cranberry formulations are better than others (111407). Most positive studies utilized oral cranberry EXTRACTS in tablet, powder, or capsule form (6760,17210,46366,46432,93669,111407). Some products (Cranberry Supreme, GNC; Cranpac, IPCA Laboratories), taken as 200 mg twice daily, were standardized to provide 100-120 mg of proanthocyanidins (PACs) daily (46432). Some of these studies used capsules containing 400 mg cranberry solids twice daily (6760) or Natural Cranberry Extract (Solgar Vitamin and Herb Co.) 800 mg twice daily (17210). However, a clinical study in healthy females with a history of UTIs shows that taking a specific cranberry extract product (Urophenol; Diana Food) does not reduce the risk of symptomatic UTI when taken at a dose of 120 mg twice daily, standardized to 15% PACs, or at a dose of 1 mg twice daily, standardized to 1% PACs. A subgroup analysis suggests that the high dose may have modest benefit in those with less than 5 UTIs a year (108054). Cranberry JUICE or syrup has yielded mixed results for the prevention of UTI in patients with a history of recurrent UTIs, with some showing significant benefit (8253,46366,96736,111407). These studies used cranberry juice 240-250 mL 1-3 times daily (46366,96736), cranberry syrup, or a combination beverage containing cranberry juice plus lingonberry juice (Maija) 50 mL daily (8253). However, other studies found no significant improvement when compared with placebo (17524,46471,90047), although some of these studies may have been inadequately powered to detect a difference (17524,46471). Cranberry products have also been compared with other treatments including antibiotics and probiotics for preventing recurrent UTI, but the results are unclear. A meta-analysis suggests that cranberry products reduce the risk of symptomatic UTIs compared to probiotics. The analysis also showed no difference in the risk of UTI between cranberry products and antibiotics, but the precision of included studies was poor (111407). In one study, taking cranberry extract capsules (Cran-Max; Proprietary Nutritionals, Inc) 500 mg daily for 6 months was as effective as trimethoprim 100 mg daily in elderly females with recurrent UTI (16720). However, taking this same cranberry product twice daily for 12 months was less effective than trimethoprim-sulfamethoxazole 480 mg once daily in younger premenopausal individuals (17176). Additional research in children with vesicoureteral reflux (VUR) shows that daily consumption of cranberry products results in UTI recurrence rates equivalent to those obtained with prophylactic antibiotics. Cranberry juice (Cranberry UR-50, Kikkoman Company) 100 mL daily was equally effective to cefaclor 5-10 mg/kg daily; cranberry syrup (Pharmatoka) 0.2 mL/kg daily was equally effective to trimethoprim 0.2 mL/kg daily (96737).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral cranberry is beneficial for age-related cognitive decline. Oral cranberry may be beneficial for improving visual episodic memory in healthy, elderly adults, but its effects on other aspects of cognition are unclear. Details: A clinical study in healthy adults aged 50-80 years shows that taking a freeze-dried cranberry powder 4.5 grams twice daily (standardized to provide 281 mg proanthocyanidins daily), provided as a sachet and added to food or beverage for 12 weeks, improves visual episodic memory performance during a memory and recall test (Rey Complex Figure Test), but does not appear to affect other measures such as attention, orientation, fluency, language, processing speed, or short-term memory, when compared with placebo (108564). Cranberry supplementation also does not appear to affect grey matter structure; however, due to the low number of patients who completed a baseline and follow-up MRI, this study may not have been adequately powered to detect a difference between groups.
• Benign prostatic hyperplasia (BPH). Preliminary clinical research suggests that oral cranberry is beneficial for reducing BPH symptoms. Details: Preliminary clinical research shows that taking powdered dried cranberry fruit 500 mg three times daily for 6 months improves lower urinary symptoms and reduces prostate specific antigen (PSA) levels when compared with no treatment in patients 45 years of age or older with elevated PSA levels, a negative prostate biopsy, and clinically confirmed non-bacterial prostatitis (17126). Another small study in those 45 years of age and older without elevated PSA levels shows that taking a specific dried cranberry powder (Flowens, Naturex-DBS, LLC) 250-500 mg daily for 6 months reduces lower urinary tract symptoms and improves voiding and storage symptoms when compared with placebo (96738).
• Cancer. Although there has been interest in using oral cranberry for cancer, there is insufficient reliable information about the clinical effects of cranberry for this condition.
• Cardiovascular disease (CVD). Although some research suggests that oral cranberry may modestly improve some CVD risk factors, it is unclear if it is beneficial for CVD prevention. Details: A meta-analysis of 10 clinical studies shows that cranberry juice or cranberry extract seems to reduce systolic blood pressure by 3.6 mmHg and body mass index by 0.3 kg/m2 when compared with placebo. However, these improvements are unlikely to be clinically significant, and cranberry does not appear to improve diastolic blood pressure, lipid levels, glycemic control, or waist circumference (102849). The generalizability of these results is limited, as the study populations ranged from healthy adults to those with type 2 diabetes, metabolic syndrome, or coronary heart disease. A clinical crossover study in patients who are overweight or obese and have elevated blood pressure shows that drinking cranberry juice 250 mL twice daily for 8 weeks reduces ambulatory diastolic blood pressure by 2 mmHg during daytime hours, but does not improve systolic blood pressure, glycemic control, or lipid levels, when compared with placebo (108059). The validity of these findings is limited due to short duration of treatment and broad heterogeneity of patient baseline characteristics.
• Catheter-related infections. Although there has been interest in using oral cranberry for catheter-related infections, there is insufficient reliable information about the clinical effects of cranberry for this condition.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral cranberry for CFS, there is insufficient reliable information about the clinical effects of cranberry for this condition.
• Diabetes. It is unclear if oral cranberry is beneficial for diabetes. Details: A small clinical trial shows that taking cranberry supplements orally does not improve fasting serum glucose, glycated hemoglobin (HbA1C), fructosamine, triglycerides, high-density lipoprotein (HDL) cholesterol, or low-density lipoprotein (LDL) cholesterol levels in patients with type 2 diabetes (11328).
• Helicobacter pylori. There is conflicting evidence regarding the use of oral cranberry for Helicobacter pylori eradication, either as a standalone treatment or in combination with standard triple therapy. Details: Two small clinical studies show that taking cranberry juice 480-500 mL, containing 88 mg proanthocyanidins (PACs), daily in two divided doses for 2-3 months can modestly increase the H. pylori eradication rate at 8 weeks, but not at 2 weeks, when compared with placebo. However, the eradication rate was only 20% or less, which is much lower than that obtained with conventional triple therapy (46388,104248). Lower doses, as either cranberry juice or cranberry powder, do not seem to improve H. pylori eradication rates. Cranberry juice containing only 23 mg or 44 mg PACs or cranberry powder containing 36 mg or 72 mg PACs did not demonstrate benefit when compared with placebo (104248). Cranberry juice has also been studied in combination with standard triple therapy. Preliminary clinical research shows that taking cranberry juice 250 mL daily for 3 weeks along with omeprazole, amoxicillin, and clarithromycin for one week does not increase the eradication rate when compared with triple therapy plus placebo. However, the combination treatment increased the rate of H. pylori eradication when only females were considered (46439). A meta-analysis of 4 small clinical studies, including three studies already discussed, shows that taking cranberry, either as a juice or a dried powder, does not improve H. pylori eradication rate when compared with placebo, regardless of treatment duration (108060). The validity of these findings is limited by the high heterogeneity of the included studies and incomplete reporting. In asymptomatic children aged 6-16 years old with H. pylori, one clinical study shows that drinking cranberry juice 200 mL, with live or heat-killed Lactobacillus johnsonii 80 mL, daily for 3 weeks eradicates H. pylori in 15% to 22% of patients, compared with 1.5% of those receiving placebo. However, these rates are lower than those typically obtained with conventional triple therapy (46441).
• Hyperlipidemia. Oral cranberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Drinking a combination of cranberry, blueberry, apple, and chokeberry juice 300 mL daily for 6 weeks appears to decrease total cholesterol and increase high-density lipoprotein (HDL) cholesterol when compared to baseline in females with overweight or obesity and at least one risk factor for cardiovascular disease (111233). However, the validity of the study is limited by its small size, short duration, and lack of a comparator group. It is unclear if these effects are due to cranberry, other ingredients, or the combination.
• Kidney stones (nephrolithiasis). It is unclear if oral cranberry is beneficial for reducing the risk of kidney stones. Details: Although some preliminary clinical research shows that drinking cranberry juice 500 mL diluted in 1500 mL water daily for 2 weeks can decrease urinary excretion of oxalate in healthy males, which suggests a decreased risk of kidney stone formation (46371), other preliminary clinical research shows that both cranberry juice and concentrated cranberry extracts can increase urinary oxalate levels, suggesting an increased risk of stone formation (7074,46393).
• Memory. It is unclear if oral cranberry is beneficial for memory. Details: Preliminary clinical research in cognitively intact older adults shows that taking cranberry juice 16 ounces twice daily for 6 weeks does not improve memory when compared with placebo (46390).
• Metabolic syndrome. It is unclear if oral cranberry is beneficial for metabolic syndrome. Details: Preliminary clinical research shows that drinking cranberry juice 240 mL twice daily for 8 weeks can increase plasma antioxidant capacity when compared with placebo in adults with metabolic syndrome. However, cranberry juice does not appear to affect blood pressure, blood glucose, serum lipids, or markers of inflammation when compared with placebo in these patients (46467).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral cranberry is beneficial for NAFLD. Details: Preliminary clinical research in adults with NAFLD shows that adding cranberry extract 288 mg daily to a weight loss diet for 12 weeks does not appear to affect body weight, liver enzymes, lipid levels, or steatosis grade when compared with placebo. Cranberry extract may moderately reduce insulin levels and insulin resistance (104249). However, the clinical impact of these reductions is unclear. Another clinical trial in adults with NAFLD shows that taking dried cranberry powder 144 mg daily after lunch for 6 months improves steatosis grade as measured by ultrasound, insulin sensitivity, and levels of total cholesterol and triglycerides, but does not affect liver enzyme levels, when compared with placebo. All patients also consumed a reduced-calorie diet and an undefined dose of supplemental vitamin E (108058).
• Obesity. Oral cranberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in females with overweight or obesity and at least one risk factor for cardiovascular disease shows that drinking a combination of cranberry, blueberry, apple, and chokeberry juice 300 mL daily for 6 weeks does not reduce body weight, body mass index (BMI), or blood pressure but might improve total cholesterol and high-density lipoprotein (HDL) cholesterol when compared to baseline (111233). However, the validity of these findings is limited by the small study size, short duration, and lack of a comparator group. It is unclear if these effects are due to cranberry, other ingredients, or the combination.
• Overactive bladder. It is unclear if oral cranberry is beneficial for overactive bladder. Details: Preliminary clinical research in otherwise healthy females shows that taking dried cranberry powder 500 mg daily for 24 weeks can reduce daily micturition by 16% and urgency episodes by 57% when compared with placebo. Patients taking cranberry powder also reported an improvement in their own perception of their bladder condition when compared with placebo (104246). Limitations of this study include a short duration, lack of a run-in period, and high drop-out rate, which interfered with the ability to meet power.
• Peristomal lesions. Although there has been interest in using oral cranberry for peristomal lesions, there is insufficient reliable information about the clinical effects of cranberry for this condition.
• Prostate cancer. It is unclear if cranberry is beneficial for preventing prostate cancer recurrence. Details: Clinical research shows that taking cranberry powder (Pacran, Naturex) 1500 mg for a mean of 30 days prior to radical prostatectomy for prostate cancer does not improve prostate tissue markers when compared with taking placebo. However, levels of prostate tissue antigen decreased by approximately 22% when compared with baseline (105127).
• Radiation-induced cystitis. Evidence for the use of cranberry juice in the prevention of radiation-induced cystitis is conflicting. Details:One small clinical study in individuals with prostate cancer shows that taking 200 mg of a cranberry extract standardized to 30% proanthocyanidins (Monoselect Macrocarpon; PharmExtracta) once daily during external beam radiotherapy for 6-7 weeks reduces the risk of lower UTI by 64% when compared with placebo (92579). However, other preliminary clinical research shows that taking cranberry capsules, standardized to contain a total of 72 mg proanthocyanidins, daily during radiation treatment for prostate cancer and for two weeks post-treatment, does not improve pain, burning, nocturia, or urinary flow symptoms from radiation-induced cystitis when compared with a beetroot placebo (104247). Additionally, preliminary clinical research in patients receiving radiotherapy for bladder or cervical cancer shows that consuming cranberry juice 250 mL daily for 2 weeks does not seem to reduce the incidence of UTIs (46469).
• Rheumatoid arthritis (RA). It is unclear if cranberry juice is beneficial in RA. Details: A clinical study in adults with RA shows that drinking reduced-calorie cranberry juice 250 mL twice daily in addition to taking fish oil 1 gram three times daily for 90 days improves disease activity score (DAS28-CRP) when compared with no supplementation. However, this combination was similarly effective to patients taking fish oil alone, suggesting that any benefits may be due to fish oil, as opposed to cranberry juice (108057).
• Upper respiratory tract infection (URTI). It is unclear if oral cranberry is beneficial for the prevention or treatment of URTIs. Details: Clinical research shows that drinking a cranberry juice beverage 450 mL daily for 70 days does not decrease the incidence of cold or flu, but may reduce cold and flu symptoms, when compared with placebo in healthy adults (90046).
• Urinary odor. It is unclear if oral cranberry is beneficial for urinary odor. Details: Preliminary clinical research shows that cranberry juice cocktail might reduce urinary odors when given orally on a regular basis to patients with urinary incontinence (3333,3334,8254). Cranberry juice cocktail up to 237 mL three times daily for up to 4 weeks has been used (3334). More evidence is needed to rate cranberry for these uses.

(Read more about CRANBERRY)

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

(Read more about JUNIPER)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Melasma. Preliminary clinical research in adults with melasma shows that applying a brewed parsley water to the face with a cotton ball on 6 days of each week for 8 weeks is as effective as hydroquinone 4% cream for improving dark spots (96828). More evidence is needed to rate parsley for this use.

(Read more about PARSLEY)

EFFECTIVE

• Hypokalemia. Oral or intravenous potassium can treat and prevent hypokalemia. Details: Administering potassium orally or intravenously is effective for treating and preventing hypokalemia (15,107970). Oral potassium 20 mEq (780 mg of elemental potassium) is typically taken once daily to prevent hypokalemia (15,95010). Oral potassium 40-100 mEq (1560-3900 mg of elemental potassium) is typically taken in 2-5 divided doses daily to treat hypokalemia (95010). Doses should be limited to 40 mEq (1560 mg of elemental potassium), and the total dose should not exceed 200 mEq (7800 mg of elemental potassium) in 24 hours (95010). Potassium supplementation and route of administration should be individualized based on serum potassium level and patient status (15,107970).

LIKELY EFFECTIVE

• Hypertension. Oral potassium, via dietary intake or supplementation, reduces blood pressure. Details: Population research has found that higher dietary potassium consumption is associated with a lower risk of developing hypertension (1310,8817,69512). Additionally, most clinical research shows that potassium, taken orally as part of the diet or as a supplement, reduces systolic blood pressure by about 3-9.5 mmHg and diastolic blood pressure by about 2-6.4 mmHg in patients with or without hypertension (3385,92104,92106,95624,107974). In most of these studies, daily intake of potassium typically ranged from about 1500-7800 mg, with the most common intake being about 2340-2540 mg daily (92104,95624). However, some research shows that taking potassium does not lower systolic or diastolic blood pressure (69541,69550,107966). Differences in the patient populations, potassium intake, and salt intake could have contributed to the conflicting results. Potassium seems to be more effective for people with hypertension, low potassium levels, high daily sodium intake, and for Black adults (3384,3385,3386,92104,92106). Some research also shows that the greatest blood pressure-lowering effects of potassium occur at doses of about 3900-7800 mg daily (95624). A meta-analysis of clinical trials using a novel computational technique to assess both potassium intake and excretion suggests that the optimal blood pressure reduction occurs when taking about 1500 mg supplemental potassium daily or an overall intake of 4500-6500 mg potassium daily (105448). This analysis is limited by the heterogeneity and short duration of the included trials. There is also interest in utilizing low-sodium, high-potassium food substitutes to treat hypertension. Research shows that using salt substitutes containing 25% to 30% potassium chloride reduces systolic and diastolic blood pressure by 3-4.6 mmHg and 1 mmHg, respectively, when compared with regular table salt (107971,107976). In 2017, the American College of Cardiology and the American Heart Association (ACC/AHA) published guidelines recommending that patients with hypertension consume 3500-5000 mg of potassium daily (95680). This intake of potassium is expected to lower systolic blood pressure by about 4-5 mmHg in patients with hypertension and by about 2 mmHg in normotensive patients (3385). Although potassium supplements and dietary potassium both seem to be beneficial, the guidelines recommend getting potassium from dietary sources, since potassium-rich diets are usually heart-healthy (95680). Additionally, the US Food and Drug Administration (FDA) has determined that foods containing at least 350 mg potassium and that are low in sodium, saturated fat, and cholesterol can state that "diets containing foods that are good sources of potassium and low in sodium may reduce the risk of high blood pressure and stroke" (1310,8817).
• Kidney stones (nephrolithiasis). Oral prescription potassium citrate reduces the risk of kidney stone recurrence. It is unclear if non-prescription potassium citrate would be beneficial. Details: The American Urological Association (AUA) recommends potassium citrate therapy for patients with recurrent calcium stones and low urinary citrate, those with recurrent calcium or calcium oxalate stones without current metabolic abnormalities, and those with uric acid or cystine stones. The citrate component reduces urine calcium excretion and increases urine citrate and urine pH, which in turn alleviates crystal growth, formation, and aggregation. Sodium citrate may also be used to prevent stone recurrence; however, due to sodium's propensity to increase urine calcium excretion, potassium citrate remains the preferred salt formulation (107972). It is important to note that potassium citrate supplements are not equivalent to prescription potassium citrate products. Dose and duration of treatment is determined by a healthcare professional and individualized based on a patient's urinary citrate levels (107975,107989). Serum potassium levels should be monitored prior to starting potassium citrate, within 2 weeks of treatment initiation, and every 12 months (107975).

POSSIBLY EFFECTIVE

• Cardiovascular disease (CVD). Eating foods high in potassium and low in sodium might reduce the risk of cardiovascular disease. It is unclear if taking potassium supplements has the same benefit. Details: Large population studies in adults without prior CVD have found that higher dietary potassium intake is associated with a lower risk of cardiovascular events (109395,109399). One study found that daily potassium intake of about 3300 mg is associated with a 13% reduction in CVD risk when compared with intake of about 1920 mg (109399). The other study found that each additional 1000 mg of daily urinary potassium excretion, which is a marker of dietary intake, is associated with an 18% reduction in CVD risk (109395). Another observational study in over 15,000 adults with history of stroke or hypertension shows that replacing regular table salt with a substitute product containing 75% sodium chloride and 25% potassium chloride for an average of 5 years decreases the rate of stroke, major cardiovascular events, or death (107976). High quality clinical trials are needed to confirm this association. The US Food and Drug Administration (FDA) has determined that foods containing at least 350 mg potassium and that are low in sodium, saturated fat, and cholesterol can state that "diets containing foods that are good sources of potassium and low in sodium may reduce the risk of high blood pressure and stroke" (1310,8817).
• Stroke. Eating foods high in potassium and low in sodium might reduce the risk of stroke. It is unclear if taking potassium supplements has the same benefit. Details: Higher dietary intake of potassium seems to be associated with a lower risk of stroke. Population research has found that increasing dietary potassium intake by 1-1.5 grams daily is associated with up to a 20% reduced risk of stroke (92105,92107). Some population research has found that higher supplemental intake of potassium is associated with a 29% reduced risk of ischemic stroke. However, supplemental potassium intake is not found to be associated with a lower risk of hemorrhagic or total stroke (92107). An observational study in over 15,000 adults with history of stroke or hypertension shows that replacing regular table salt with a substitute product containing 75% sodium chloride and 25% potassium chloride for an average of 5 years decreases the rate of stroke, major cardiovascular events, or death (107976). High quality clinical trials are needed to confirm this association. The US Food and Drug Administration (FDA) has determined that foods containing at least 350 mg potassium and that are low in sodium, saturated fat, and cholesterol can state that "diets containing foods that are good sources of potassium and low in sodium may reduce the risk of high blood pressure and stroke" (1310,8817).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dental hypersensitivity. It is unclear if topical potassium improves dental hypersensitivity. Details: One meta-analysis of clinical research shows that using a dentifrice containing 5% potassium nitrite reduces dentin sensitivity when compared with a dentifrice that does not contain potassium nitrite (69549). Other clinical research published in a systematic review shows that potassium-containing toothpastes might reduce dentin sensitivity more than controls that do not contain potassium. However, these toothpastes might be less effective than other active toothpastes, such as those containing sodium monofluorophosphate, and the effect may result from a placebo effect, since the mechanism of action of potassium is unclear (69456).
• Diabetes. It is unclear if increasing dietary potassium reduces the risk of diabetes. Details: A meta-analysis of 7 large population studies has found that consuming dietary potassium 3300-3500 mg daily is associated with a 20% reduction in the risk of diabetes when compared with consumption below 1000 mg daily. Results were similar when studies that measured potassium intake with a dietary questionnaire were analyzed separately from those that measured intake based on urinary potassium excretion (110776). However, the validity of this finding is limited by the heterogeneity of the included studies. Furthermore, despite use of data from various databases, most studies included in the analysis were conducted by the same author.
• Impaired glucose tolerance (prediabetes). It is unclear if oral potassium improves glycemic control in prediabetes. Details: A small clinical study in Black patients with prediabetes shows that taking extended-release potassium (Klor-Con M10, Cardinal Health) 40 mEq daily as potassium chloride for 3 months does not improve glucose tolerance when compared with placebo. Although fasting glucose levels were slightly reduced in the potassium group when compared with placebo, both groups experienced a worsening of glucose intolerance, with no change in insulin levels or glycated hemoglobin (98533).
• Osteoporosis. Although there is interest in using oral potassium for osteoporosis, there is insufficient reliable information about the clinical effects of potassium for this condition.
• Physical performance. It is unclear if oral potassium improves physical performance in older adults. Details: Observational research in older adults has found that decreased dietary potassium intake and increased dietary sodium intake over 5 years is associated with worsened physical performance (105450).
• Systemic lupus erythematosus (SLE). It is unclear if oral potassium is beneficial in patients with SLE. Details: Observational research in patients with SLE has found that increased dietary potassium intake is not associated with improvements in disease activity scores or markers of cardiovascular disease, including lipid levels and blood pressure, when compared with low dietary potassium intake. However, higher potassium intake does seem to reduce the odds of having elevated levels of C-reactive protein, a marker of inflammation, in these patients (109397). More evidence is needed to rate potassium for these uses.

(Read more about POTASSIUM)

POSSIBLY INEFFECTIVE

• Urinary tract infections (UTIs). Clinical research does not support the use of oral uva ursi for treatment of UTIs. For prevention of UTIs, oral uva ursi has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in females with uncomplicated UTI shows that taking uva ursi tablets providing 210 mg arbutin orally three times daily for 5 days is less effective than a single dose of fosfomycin 3 grams for reducing UTI symptom burden and the number of rescue antibiotic courses. Rescue antibiotics were needed in 44% of patients receiving uva ursi, compared with 23% of those receiving fosfomycin. On day 4, the percentage of patients with symptom resolution was 49% with uva ursi, compared to 65% with fosfomycin. Pyelonephritis occurred in 8 patients on uva ursi and 2 patients on fosfomycin (109535). Also, a large clinical study in females experiencing symptoms of a UTI shows that taking uva ursi extract 1200 mg three times daily for 3-5 days does not improve symptoms or reduce the need for antibiotics when compared with placebo (101815). Uva ursi has also been evaluated for the prevention of UTIs. One small clinical study in females with recurrent UTI shows that taking a specific combination product containing uva ursi and dandelion (UVA-E, Medic Herb AB) 3 tablets three times daily for one month reduces the recurrence rate of UTIs when compared with placebo (1932). It is not clear if this effect is due to uva ursi, dandelion, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Benign prostatic hyperplasia (BPH). Although there is interest in using oral uva ursi for BPH, there is insufficient reliable information about the clinical effects of uva ursi for this condition.
• Bronchitis. Although there is interest in using oral uva ursi for bronchitis, there is insufficient reliable information about the clinical effects of uva ursi for this condition. More evidence is needed to rate uva ursi for these uses.

(Read more about UVA URSI)

LIKELY SAFE ...when the leaf is used in amounts commonly found in foods. Buchu has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912).

POSSIBLY SAFE ...when the leaf is used orally and appropriately in medicinal amounts (2,12).

POSSIBLY UNSAFE ...when excessive amounts of buchu leaf are taken orally or when the oil is ingested. Buchu contains pulegone, a known hepatotoxin (4). Pulegone is a major component of the oil. It is more abundant in buchu products that come from Agathosma crenulata (93681).

PREGNANCY: LIKELY UNSAFE
when used in medicinal amounts; buchu is reported to be an abortifacient (4).

LACTATION: POSSIBLY SAFE
when used in food amounts. There is insufficient reliable information available about the safety of using larger amounts; avoid using.

(Read more about BUCHU)

LIKELY SAFE . .when used orally and appropriately. Cranberry juice up to 300 mL daily and cranberry extracts in doses up to 800 mg twice daily have been safely used in clinical trials (3333,3334,6758,6760,7008,8252,8253,8254,8995,11328) (16415,16720,17100,17126,17176,17210,17524,46379,46388,46389)(46390,46425,46439,46443,46465,46456,46466,46467,46469,46471)(46496,46499,90044,102847,111407).

CHILDREN: LIKELY SAFE
when cranberry juice is consumed in amounts commonly found in the diet (2811,6759,46441,46452,46470,111407). There is insufficient reliable information available about the safety of cranberry when used in medicinal amounts in children.

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in the diet. There is insufficient reliable information available about the safety of cranberry when used therapeutically during pregnancy or lactation; avoid using.

(Read more about CRANBERRY)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Juniper, juniper berry, and juniper extract have Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used topically on limited areas of skin (12230). ...when the oil is used by inhalation and appropriately as aromatherapy (7107). There is insufficient reliable information available about the safety of juniper when used orally in doses of less than 10 grams of berries or 100 mg of oil daily, short-term. Juniper oil and berry have a long history of traditional use (12,103759).

LIKELY UNSAFE ...when used orally in excessive amounts or long-term. Use of daily doses greater than 10 grams of juniper berries (about 60 berries) or 100 mg of juniper essential oil, or prolonged oral use longer than 4 weeks, have been reported to increase the risk of severe adverse effects such as convulsions or kidney damage (8,19,103759).

PREGNANCY: UNSAFE
when used orally. Juniper can increase uterine tone, interfere with fertility and implantation, and cause abortion (4,19).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about JUNIPER)

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

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term (12,13173).

LIKELY UNSAFE ...when used orally in very large doses e., 200 grams). Parsley oil contains significant amounts of the potentially toxic constituents, apiole and myristicin (11). Apiole can cause blood dyscrasias, kidney toxicity, and liver toxicity; myristicin can cause giddiness and hallucinations (4). ...when parsley seed oil is used topically. Applying parsley seed oil to the skin can cause photodermatitis upon sun exposure (4). There is insufficient reliable information available about the safety of the topical use of parsley leaf and root.

PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts. Parsley has been used orally as an abortifacient and to stimulate menstrual flow (4,12,515,19104,92873). Population evidence suggests that maternal intake of An-Tai-Yin, an herbal combination product containing parsley and dong quai, during the first trimester increases the risk of congenital malformations of the musculoskeletal system, connective tissue, and eyes (15129).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about PARSLEY)

LIKELY SAFE ...when used orally in doses up to 100 mEq total potassium daily, not to exceed 200 mEq in a 24-hour period (95010,107989). Oral potassium chloride and potassium citrate are FDA-approved prescription products (95010,107989). Larger doses increase the risk of hyperkalemia (15). ...when administered intravenously (IV) at appropriate infusion rates (95011). Parenteral potassium is an FDA-approved prescription product (15,95011). A tolerable upper intake level (UL) for potassium has not been established; however, potassium levels should be monitored in individuals at increased risk for hyperkalemia, such as those with kidney disease, heart failure, and adrenal insufficiency (100310,107966).

CHILDREN: LIKELY SAFE
when used orally and appropriately in dietary amounts. A tolerable upper intake level (UL) has not been established for healthy individuals (6243,100310).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in dietary amounts of 40-80 mEq daily (15). A tolerable upper intake level (UL) has not been established for healthy individuals (100310).

(Read more about POTASSIUM)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Uva ursi has been used with apparent safety in doses of up to 3600 mg daily for 3-5 days (101815).

POSSIBLY UNSAFE ...when used orally long-term or in high doses. There is concern about the safety of long-term or high-dose use because of the hydroquinone content of uva ursi. Hydroquinone is thought to have mutagenic and carcinogenic effects (7). At high doses (around 20 grams of dried herb) it can cause convulsions, cyanosis, delirium, shortness of breath, and collapse. At very high doses (30 grams of dried herb or more) it can be fatal (4).

CHILDREN: POSSIBLY UNSAFE
when used orally by children. Uva ursi contains hydroquinone and high tannin levels, which can cause severe liver problems in children (4,18); avoid using.

PREGNANCY: LIKELY UNSAFE
when used orally. Uva ursi can have oxytocic effects, increasing the speed of labor (4,7,19); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about UVA URSI)

(Read more about BUCHU)

ATORVASTATIN (Lipitor) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cranberry might increase levels and adverse effects of atorvastatin.  Details In one case report, a patient taking atorvastatin experienced upper back pain, rhabdomyolysis, and abnormal liver function after drinking cranberry juice 16 ounces daily for 2 weeks. Theoretically, this may have been caused by inhibition of cytochrome P450 3A4 (CYP3A4) enzymes by cranberry juice, as atorvastatin is a CYP3A4 substrate. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice (90042). Patients taking atorvastatin should avoid large quantities of cranberry juice.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, cranberry might increase the levels and adverse effects of CYP2C9 substrates. However, research is conflicting.  Details There is contradictory evidence about the effect of cranberry on CYP2C9 enzymes. In vitro evidence suggests that flavonoids in cranberry inhibit CYP2C9 enzymes (10452,11115,90048). However, clinical research shows that cranberry juice does not significantly affect the levels, metabolism, or elimination of the CYP2C9 substrates flurbiprofen or diclofenac (11094,90048). Also, in patients stabilized on warfarin, drinking cranberry juice 250 mL daily for 7 days does not significantly increase the anticoagulant activity of warfarin, a CYP2C9 substrate (15374). Additional pharmacokinetic research shows that cranberry juice does not increase peak plasma concentrations or area under the concentration-time curve of warfarin (15393).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cranberry might increase the levels and adverse effects of CYP3A4 substrates.  Details A case of upper back pain, rhabdomyolysis, and abnormal liver function has been reported for a patient taking atorvastatin, a CYP3A4 substrate, in combination with cranberry juice 16 ounces daily for 2 weeks. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice (90042). Also, animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine, a CYP3A4 substrate, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control (46420).

DICLOFENAC (Voltaren, others) Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, cranberry might modestly increase the levels and adverse effects of diclofenac.  Details In vitro evidence suggests that cranberry juice inhibits diclofenac metabolism by human liver microsomes (90048). However, drinking cranberry juice does not seem to affect diclofenac metabolism in humans (90048).

NIFEDIPINE (Procardia) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cranberry might increase the levels and adverse effects of nifedipine.  Details Animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine treatment, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control (46420). This interaction has not been reported in humans.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, cranberry might increase the levels and adverse effects of warfarin. However, research is conflicting.  Details There is contradictory evidence about the effect of cranberry juice on warfarin. Case reports have linked cranberry juice consumption to increases in the international normalized ratio (INR) in patients taking warfarin, resulting in severe spontaneous bleeding and excessive postoperative bleeding (10452,12189,12668,21187,21188,21189,46378,46396,46411)(46415,90043). Daily consumption of cranberry sauce for one week has also been linked to an increase in INR in one case report (16816). In a small study in healthy young males, taking a high dose of 3 grams of cranberry juice concentrate capsules, equivalent to 57 grams of fruit daily, for 2 weeks produced a 30% increase in the area under the INR-time curve after a single 25-mg dose of warfarin (16416). However, 3 very small clinical studies in patients stabilized on warfarin reported that cranberry juice 250 mL once or twice daily for 7 days (27% cranberry juice or pure cranberry juice) or 240 mL once daily for 14 days does not significantly increase INR or affect plasma warfarin levels (15374,17124,90045). The reasons for these discrepant findings are unclear. It is possible that the form and dose of cranberry may play a role, as cranberry extracts and juices contain different constituents. Additionally, an in vitro study evaluating 5 different cranberry juices found varying effects, with only a cranberry concentrate, and not diluted cranberry juices, inhibiting CYP2C9. However, this concentrate did not inhibit CYP2C9 activity in humans (108062).

(Read more about CRANBERRY)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Animal research suggests that juniper berry has hypoglycemic activity (4). Theoretically, taking juniper berry with antidiabetes medications might cause additive blood glucose reduction. Monitor blood glucose levels closely. Dose adjustments to antidiabetes medications might be necessary.  Details Some antidiabetes drugs include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), and others.

DIURETIC DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Juniper berry can cause the body to lose water. Theoretically, juniper berry might increase the effectiveness of diuretic therapy, causing the body to lose too much water and increasing the likelihood of experiencing side effects (4, 512).  Details Some diuretic drugs include chlorothiazide (Diuril), chlorthalidone (Thalitone), furosemide (Lasix), hydrochlorothiazide (HCTZ, Hydrodiuril, Microzide), and others.

(Read more about JUNIPER)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Animal research suggests that parsley has antiplatelet effects (68209). Theoretically, concomitant use of parsley with other anticoagulant/antiplatelet drugs might reduce platelet aggregation and increase the risk of bleeding.  Details Some anticoagulant/antiplatelet drugs include aspirin, clopidogrel (Plavix), ticagrelor (Brilinta) diclofenac (Voltaren, Cataflam), ibuprofen (Advil, Motrin), naproxen (Anaprox, Naprosyn), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Laboratory research suggests that parsley can inhibit cytochrome P450 1A2 (CYP1A2) (68176). Theoretically concomitant use may increase the levels of CYP1A2 substrates.  Details Some drugs metabolized by CYP1A2 include amitriptyline (Elavil), haloperidol (Haldol), ondansetron (Zofran), propranolol (Inderal), theophylline (Theo-Dur, others), verapamil (Calan, Isoptin, others), and others.

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Animal research suggests that parsley seed extract increases urine elimination (68119). Theoretically, parsley leaf and root might interfere with diuretic therapy due to aquaretic effects (512).  Details Some diuretic drugs include chlorothiazide (Diuril), chlorthalidone (Thalitone), furosemide (Lasix), hydrochlorothiazide (HCTZ, HydroDiuril, Microzide), spironolactone (Aldactone), triamterene (Dyrenium), and others.

(Read more about PARSLEY)

ACE INHIBITORS (ACEIs) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = C Using ACEIs with high doses of potassium increases the risk of hyperkalemia.  Details ACEIs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion (95628). Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia (15,23207). However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels (95628).

ANGIOTENSIN RECEPTOR BLOCKERS (ARBs) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = C Using ARBs with high doses of potassium increases the risk of hyperkalemia.  Details ARBs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion (95628). Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia (15,23207). However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels (95628).

POTASSIUM-SPARING DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = C Concomitant use increases the risk of hyperkalemia.  Details Using potassium-sparing diuretics with potassium supplements increases the risk of hyperkalemia (15).

(Read more about POTASSIUM)

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, uva ursi may decrease the metabolism of CYP2C19 substrates.  Details In vitro, uva ursi appears to inhibit cytochrome CYP2C19 (98550). This effect has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, uva ursi may decrease the metabolism of CYP3A4 substrates.  Details In vitro, uva ursi appears to inhibit CYP3A4 (98550). This effect has not been reported in humans.

GLUCURONIDATED DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, uva ursi may increase levels of drugs metabolized by glucuronidation.  Details In vitro, uva ursi extract appears to strongly inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1). However, uva ursi extract does not appear to inhibit UGT1A1 in animal models (98549). This effect has not been reported in humans.

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, uva ursi may increase lithium levels, necessitating a decrease in dose.  Details Uva ursi may have diuretic properties (81637). Diuretics may increase lithium reabsorption with sodium in the proximal tubule of the kidney. Theoretically, uva ursi might reduce excretion and increase levels of lithium.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, uva ursi may alter the levels of drugs transported by P-glycoprotein.  Details In vitro, uva ursi appears to inhibit the multi-drug transporter protein, P-glycoprotein (98550). This effect has not been reported in humans.

URINARY ACIDIFYING AGENTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Effects of uva ursi in the urinary tract may be reduced by urinary acidifying agents.  Details Uva ursi seems to work best in alkaline urine. Theoretically, taking uva ursi with medications known to acidify the urine may decrease any effects of uva ursi on the urinary tract (19).

(Read more about UVA URSI)

General ...Orally, buchu leaf can cause GI and kidney irritation (4,6) and increase menstrual flow (6). Buchu is also a reported abortifacient (4).

Gastrointestinal ...Orally, buchu may cause gastrointestinal irritation (4,6).

Genitourinary ...Orally, buchu may increase menstrual flow (6). Buchu is also a reported abortifacient (4).

Renal ...Orally, buchu may cause kidney irritation (4,6).

(Read more about BUCHU)

General ...Orally, cranberry seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea and gastrointestinal discomfort.

Dermatologic ...Orally, skin redness and itching has been reported in one patient (46389).

Gastrointestinal ...In very large doses, for example 3-4 L per day of juice, cranberry can cause gastrointestinal upset and diarrhea, particularly in young children (46364). There are reports of abdominal and gastrointestinal discomfort after taking cranberry tablets, extracts, and juice in clinical trials (16720,46379,111407). Nausea, vomiting, and diarrhea have also been reported with consumption of lower doses of cranberry juice cocktail, 16 ounces per day, equivalent to about 4 ounces cranberry juice, for several weeks (16415).

Genitourinary ...Vulvovaginal candidiasis has been associated with ingestion of cranberry juice (46374). Clinical research suggests that ingestion of cranberry juice may be associated with vaginal itching and vaginal dryness (46471). One patient in clinical research stopped taking dried cranberry juice due to excessive urination (46437), and an isolated case of nocturia following ingestion of cranberry tablets has been reported (16720).

Hematologic ...Thrombocytopenia has been reported as an adverse event to cranberry juice (46459).

Other ...An isolated case of sensitive swollen nipples after taking cranberry tablets has been reported (16720).

(Read more about CRANBERRY)

General ...Orally and topically, juniper seems to be generally well tolerated when used short-term. However, a thorough evaluation of safety outcomes has not been conducted. Most reported adverse effects are related to ingestion of excessive amounts of juniper berry oil. Symptoms of overdose include kidney pain and irritation, diuresis, albuminuria, hematuria, purplish urine, tachycardia, hypertension, convulsions, metrorrhagia, and abortion (4). Topically, juniper can cause skin irritation (4,103756). Repeated exposure to the juniper pollen can cause occupational allergies (6).

Dermatologic ...Topically, juniper can cause skin irritation. Signs of topical poisoning include burning, erythema, inflammation with blisters, and edema (4). Repeated exposure to the juniper pollen can cause occupational allergies that affect the skin (6). In a case report, a 62-year-old woman developed burn-like blistering lesions after carrying juniper in close contact to her skin. Concurrent sun exposure was thought to worsen the skin irritation caused by juniper (103756).

Genitourinary ...Orally, large amounts of the juniper berry can cause purplish urine (4).

Pulmonary/Respiratory ...Repeated exposure to the juniper pollen can cause occupational allergies that affect the respiratory tract (6).

(Read more about JUNIPER)

General ...Orally, parsley seems to be well tolerated when used low to moderate doses. In rare cases, allergy to parsley has been reported (92869,92870). In large doses (i.e., 200 grams) parsley oil may cause significant adverse effects due to its potentially toxic constituents, apiole and myristicin (11). Adverse effects specifically associated with more than 10 grams of the constituent apiole include hemolytic anemia, thrombocytopenia purpura, nephrosis, hepatic dysfunction, and kidney irritation (4). Adverse effects specifically associated with the constituent myristicin include giddiness, deafness, hallucinations, hypotension, bradycardia, paralysis, and fatty degeneration of the liver and kidneys (4). Parsley oil can also cause contact photodermatitis with sun exposure (4).
Topically, parsley can cause contact photodermatitis (4).

Cardiovascular ...Parsley contains the potentially toxic constituent, myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with myristicin include hypotension and bradycardia (4).

Dermatologic ...Orally, parsley oil can cause contact photodermatitis with sun exposure (4).
Topically, parsley can cause contact photodermatitis (4).

Hematologic ...Parsley contains the potentially toxic constituent apiole, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with more than 10 grams of the constituent apiole include hemolytic anemia and thrombocytopenia purpura (4).

Hepatic ...Parsley contains the potentially toxic constituents, apiole and myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with more than 10 grams of the constituent apiole include hepatic dysfunction (4). Adverse effects specifically associated with the constituent myristicin include fatty degeneration of the liver (4).

Immunologic ...A case of anaphylaxis involving severe angioedema leading to unconsciousness has been reported in a woman who consumed parsley 45 minutes prior to symptoms. The patient responded to epinephrine, antihistamines, intravenous fluids, oxygen therapy, and 1 mg/kg methylprednisolone. The woman had consumed one cup of chopped parsley nearly every day for several years, but upon skin testing, the patient tested positive to parsley (92869). There is also a report of lip angioedema after consumption of raw parsley. The patient had anaphylaxis to raw arugula, and reported itchy red lesions after contact with the leaves of either raw parsley or arugula. The patient had positive skin prick tests to both plants. The reaction may have been due to oral allergy syndrome, as the patient could tolerate cooked arugula and parsley, but not raw (92870).

Ocular/Otic ...Parsley contains the potentially toxic constituent, myristicin, which can cause significant adverse effects at high doses (11). An adverse effect specifically associated with the constituent myristicin includes deafness (4).

Psychiatric ...Parsley contains the potentially toxic constituent, myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with the constituent myristicin include giddiness and hallucinations (4).

Renal ...Parsley contains the potentially toxic constituents, apiole and myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with more than 10 grams of the constituent apiole include nephrosis and kidney irritation (4). Adverse effects specifically associated with the constituent myristicin include fatty degeneration of the kidneys (4).

(Read more about PARSLEY)

General ...Orally or intravenously, potassium is generally well-tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, belching, diarrhea, flatulence, nausea, and vomiting.
Serious Adverse Effects (Rare):
All ROAs: High potassium levels can cause arrhythmia, heart block, hypotension, and mental confusion.

Cardiovascular ...Orally or intravenously, high potassium levels can cause hypotension, cardiac arrhythmias, heart block, or cardiac arrest (15,16,3385,95011,95626,95630).

Gastrointestinal ...Orally or intravenously, high doses of potassium can cause, nausea, vomiting, abdominal pain, diarrhea, and flatulence (95010,95011). Bleeding duodenal ulcers have also been associated with ingestion of slow-release potassium tablets (69625,69672).

Neurologic/CNS ...Orally or intravenously, high potassium levels can cause paresthesia, generalized weakness, flaccid paralysis, listlessness, vertigo, or mental confusion (15,16,3385,95011).

(Read more about POTASSIUM)

General ...Uva ursi is generally well tolerated in low doses, short-term.
Most Common Adverse Effects:
Orally: Diarrhea, nausea, stomach upset, and vomiting.
Serious Adverse Effects (Rare):
Orally: At high doses (20 grams of dried herb), uva ursi has been reported to cause collapse, convulsions, cyanosis, delirium, shortness of breath, and tinnitus. Very high doses of 30 grams or more may be fatal.

Gastrointestinal ...Orally, uva ursi may cause nausea, vomiting, diarrhea, and stomach upset (92148). It can also irritate the gastrointestinal tract (19).

Genitourinary ...Orally, uva ursi may cause the urine to be greenish-brown. It may also cause irritation and inflammation of the urinary tract mucous membranes (18).

Hepatic ...Uva ursi may be hepatotoxic. Theoretically, chronic use, especially in children, can cause liver impairment due its hydroquinone and high tannin content (4,18).

Neurologic/CNS ...Orally, around 20 grams of uva ursi is reported to supply up to one gram of hydroquinone, which can theoretically cause convulsions and delirium (4).

Ocular/Otic ...Orally, uva ursi may potentially cause retinal toxicity due to its hydroquinone content, which reduces melanin synthesis. A 56-year-old female developed bilateral bull's-eye maculopathy, paracentral scotomas, and retinal thinning after 3 years of uva ursi tea ingestion (16900).
Taking around 20 grams of uva ursi orally is reported to supply up to one gram of hydroquinone, which can theoretically cause tinnitus (4).

Pulmonary/Respiratory ...Orally, around 20 grams of uva ursi is reported to supply up to one gram of hydroquinone, which can theoretically cause shortness of breath and cyanosis (4).

(Read more about UVA URSI)