Laso Tea Instant Raspberry Lemonade by Total Life Changes

POSSIBLY EFFECTIVE

• Athletic performance. Oral beet may improve athletic performance associated with aerobic activities. However, it is not clear who is most likely to benefit, for which type of competition it is most useful, or what dose or duration of use is most appropriate. Details: Several small clinical trials, most of which enrolled elite athletes, recreational athletes, and sedentary males, as well as meta-analyses of some of these and other studies, show that beet improves various measures of athletic performance, including ability, muscular endurance, power output, sprinting, and strength (93844,94464,94468,94469,100143,100150,100152,105761,113422). Clinical research also shows that drinking beetroot juice improves the use of oxygen during exercise testing in recreationally-trained athletes, especially with severe exercise testing (94460,94463,94467,100147,105762). Also, in obese adolescents, taking beetroot juice daily for 6 days increases the time to exhaustion from severe exercise, but does not improve moderate exercise (100145). Not all research shows that beet supplementation benefits athletic performance. Another meta-analysis of several small clinical studies, including some of the studies above, shows that taking beetroot does not improve performance in high-intensity or sprint interval training (111159). Additionally, the majority of research in elite athletes does not support the use of beetroot juice to decrease the time needed to complete a task, aid in some sort of graded exercise test, or improve the use of oxygen during exercise testing (94455,94458,94460,94461,94464,94465,94466,94469,94473,100142,100153,105763). The supposed lack of effect of beetroot juice in elite athletes might be related to the natural production of nitrates and nitrites in the body or the increased ability to use oxygen that comes from extensive training (94458,94463). Alternatively, any changes might be very small (<1%) and not identified with statistical comparisons, although even very small changes might be beneficial in competition (94464). The most commonly used doses in all studies, regardless of effect, have included an acute dose of beetroot juice 70-500 mL up to 3 hours prior to exercise (93844,94463,94464,94466,94467,94473,97726,100142,100143,105761)(105762,111159,113422) or chronic dosing of up to 500 mL daily for 3-6 days (94459,94464,94469,100145,100147,100153,111159,113422). Less commonly, beetroot juice 70-140 mL daily, betalain-rich concentrate 100 mg daily, or a beetroot-based nutritional gel 100 grams daily, have been taken for longer dosing schedules of 7-15 days (97720,100144,100148,100152,105763,113422). Benefits in elite athletes, most often related to time trials, are usually limited to studies using chronic dosing of 7-15 days, which is longer than the duration of 6 days used in the majority of studies (94473,97720,100144,100148). Brands of juice used in clinical trials have included Beet It Sport (James White Drinks Ltd.) (94455,94458,94465,100142,100143,100144,100148,105761,105763), Beet It Stamina Shot (James White Drinks Ltd.) (93844), Beet It (James White Drinks Ltd) (94457,94459,94460,94467,94469,97726,100145,100153,105762,111159), and Love Beets Beetroot Juice (Gs Fresh Ltd.) (94461,94462). Although plasma levels have not been analyzed in all studies, the majority of studies suggest that these doses are adequate to increase levels of nitrates or nitrites, which is thought to be essential for increasing athletic potential (93844,94455,94458,94459,94460,94465,94467,94469,94466,94473,97726). The evidence also suggests benefit in both normoxic and hypoxic environments (94465,100148,105763).
• Exercise-induced muscle soreness. Drinking beetroot juice 7-8 times over 48 hours after strenuous exercise may reduce exercise-induced muscle soreness, but evidence is conflicting. Details: Some clinical research shows drinking beetroot juice (Love Beets Beetroot Juice, Gs Fresh Ltd.) 125 mL or 250 mL seven times over 48 hours after strenuous box jumps improves muscle soreness when compared with placebo and sodium nitrite (96964,97722). Other small clinical studies show that drinking beetroot juice 50-250 mL as eight separate doses over 48 hours after strenuous exerciseimproves muscle soreness and reduces tissue edema when compared with placebo (94461,113424). However, drinking beetroot juice 250 mL as seven separate doses over 48 hours after running a marathon does not appear to reduce muscle soreness when compared with placebo (94462). A meta-analysis of 4 small studies, mostly in healthy or physically active males, shows that drinking beetroot juice improves the pressure pain threshold, which is a measure of muscle soreness, at 48- and 72-hours post-exercise when compared with a fruit-flavored drink. However, beetroot juice does not improve subjective muscle soreness scores (111160). The validity of the findings from this meta-analysis is limited by the heterogeneity of the beetroot juice regimens among the included studies. Further, these results should not be generalized to elite athletes.

POSSIBLY INEFFECTIVE

• Chronic obstructive pulmonary disease (COPD). Drinking beetroot juice for up to 14 days may not improve exercise capacity in patients with COPD. Details: A meta-analysis of eight small clinical trials in patients with COPD shows that taking nitrate-rich beetroot juice does not improve most measures of exercise capacity, including the 6-minute walk test, cycling ergometry endurance time, and maximum rate of oxygen consumption (VO2 max), when compared with placebo. Additionally, beetroot juice did not reduce blood pressure or heart rate. However, the analysis did show a significant improvement in scores on the Borg Rating of Perceived Exhaustion scale with beetroot juice over placebo. Nitrate-rich beetroot juice doses ranged from 70-140 mL daily for up to 14 days (104200).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cognitive function. It is unclear if drinking beetroot juice is beneficial for cognitive function. Details: A small clinical study in adults with overweight or obesity on a calorie-restricted diet shows that drinking 70 mL of concentrated beetroot juice daily for 14 days improves the time to complete part B of the trail making test, which is a test of cognitive function, but not part A, when compared with controls (111158). However, the duration and size of this study limits its validity. Further, it is unclear whether any improvement is clinically significant. The effect of acute beet administration on cognitive function has also been studied. A very small clinical study in healthy adults shows that taking beet extract (RedNite, Enovate Biolife) chewable tablets 3 grams 90 minutes prior to neuropsychological testing improves immediate and delayed memory capacity, frontal lobe function, and lexical flexibility but does not improve working memory, information processing speed, or subjective reports of memory performance when compared with placebo (113427).
• Coronary heart disease (CHD). It is unclear if oral beetroot extract is beneficial in patients with CHD. Details: A small clinical trial in patients with CHD shows that taking red beetroot extract 500 mg, containing around 25 mg betalains, twice daily for 2 weeks reduces total cholesterol and low-density lipoprotein (LDL) cholesterol by 15 mg/dL and reduces triglycerides by 8 mg/dL when compared to baseline. Slight improvements in blood pressure and blood glucose were also reported, but these changes were not clinically significant (103883). The validity of these findings is limited by the lack of a comparator group. Also, it is unclear whether beetroot can reduce the risk of cardiovascular events in patients with CHD.
• Dyslipidemia. It is unclear if oral beetroot is beneficial in patients with dyslipidemia. Details: A meta-analysis of small clinical studies in healthy individuals or patients with dyslipidemia, cardiovascular disease, or overweight or obesity, shows that consuming beetroot juice or leaves does not improve levels of triglycerides or total, low-density lipoprotein, or high-density lipoprotein cholesterol when compared with controls (111163). However, the validity of the findings from this meta-analysis is limited by the heterogeneity of the enrolled patients and beetroot regimens.
• Exercise-induced muscle damage. It is unclear if oral beetroot juice improves recovery from muscle damage after exercise. Details: A meta-analysis of 4 small clinical studies in healthy or physically active individuals, most of which enrolled males only, shows that drinking beetroot juice improves measures of muscle recovery at 72 hours post-exercise when compared with a fruit-flavored drink. However, beetroot juice does not consistently improve recovery at earlier time points post-exercise, nor does it reduce levels of creatine kinase or markers of inflammation (i.e., interleukin-6, interleukin-8, c-reactive protein, or tumor necrosis factor-alpha) (111160). However, the validity of the findings from this meta-analysis is limited by the heterogeneity of the beetroot juice regimens among the included studies, which usually varied from 210-250 mg of nitrate in 7-11 servings over 3-7 days. Further, these results should not be generalized to elite athletes. Another very small clinical study in semi-professional female athletes shows that ingesting beetroot juice 50 mL 8 times over 48 hours after exercise-induced muscle damage enhances the recovery of some functional parameters such as muscle endurance but not others such as flexibility and vertical jump performance when compared with placebo (113424).
• Hypertension. Oral beet may slightly reduce blood pressure in healthy individuals, but it is unclear if it is beneficial in patients with hypertension. Details: Meta-analyses of small studies show the potential for a minor reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in healthy adults taking beetroot juice (94470,97718,97728). The average reduction in SBP and DBP with beetroot juice consumption is about 4 mmHg and 1 mmHg, respectively, which is greater than the effect seen with consuming blackcurrant juice or nitrate-depleted beetroot juice. The most benefit is seen when beetroot juice is taken for at least 2 weeks or at doses of 500 mL daily (97728). The effect of acute beet supplementation on blood pressure is conflicting. A small clinical study in healthy adults shows that drinking beet juice (Beet It, James White Company) 140 mL two hours prior to cardiovascular measurements reduces resting SBP by about 4 mmHg but does not improve resting or post-exercise DBP, central blood pressure, or arterial stiffness nor does it improve post-exercise SBP when compared with placebo. Subgroup analysis suggests that the reductions in resting SBP were only observed in males, not females (113423). Another small clinical study shows that consuming beet 100 grams baked into bread modestly decreases DBP over a 6-hour period when compared with white bread (97725). It is possible that genetics might play a role in the magnitude of effect seen with beetroot consumption. Adults with a specific gene polymorphism, eNOS Glu298Asp, experienced a greater reduction in DBP after consuming beet-containing bread (97724). Despite positive findings in studies of healthy individuals, research on the use of beetroot juice in patients with hypertension is unclear. A small clinical study in adults with hypertension who were taking antihypertensive medications shows that drinking nitrate-rich beetroot juice (Beet it; James White Drinks Ltd.) 70 mL twice daily for one week does not lower blood pressure when compared with nitrate-depleted beetroot juice (94457). Also, in patients with mild to moderate hypertension, clinical research shows that taking a combination of beetroot powder (Sensient) 300 mg, olive leaf extract 1000 mg, and green coffee bean extract 200 mg daily for 6 weeks does not lower blood pressure when compared with placebo (97723). However, some evidence suggests that at least part of the blood pressure lowering effects of beet might be independent of nitrate (97728). Furthermore, some research suggests that identifying effects on blood pressure might be dependent on the method of measurement, including clinic resting measurements, 24-hour monitoring, or morning/evening home resting measurements (97729).
• Hypertriglyceridemia. It is unclear if oral beet is beneficial in patients with hypertriglyceridemia. Details: A small clinical study in overweight or obese individuals with dyslipidemia shows that taking freeze-dried beet leaf 2.8 grams daily for 4 weeks in addition to nutritional guidance does not lower triglyceride levels when compared with nutritional guidance alone (100146). Beet has also been evaluated in combination with other ingredients. A small clinical trial in patients at risk for heart disease shows that a specific combination of beet and hawthorn berry (Neo40-Daily, Neogenis Labs), taken twice daily for 30 days, can modestly reduce blood triglyceride levels when compared to baseline (18222). It is unclear if these findings are due to beet, hawthorn berry, or the combination.
• Liver disease. Although there has been interest in using oral beet for liver disease, there is insufficient reliable information about the clinical effects of beet for this purpose.
• Muscle strength. It is unclear if oral beetroot juice is beneficial for muscle strength. Details: A meta-analysis of 18 clinical studies in healthy males shows that taking beetroot juice or beetroot gel 2-3 hours before exercise improves muscular strength when compared with placebo. Subgroup analysis suggests that beetroot-based supplements improve muscular strength in a fatigued but not resting state (113422). A small clinical study in adults with overweight or obesity on a calorie-restricted diet shows that drinking 70 mL of concentrated beetroot juice daily for 14 days improves handgrip strength by approximately 18% compared with 4% in controls (111158). However, it is unclear whether any improvement is clinically significant.
• Obesity. It is unclear if oral beet leaf or beetroot juice is beneficial for weight loss. Details: A small clinical study in patients with overweight or obesity and dyslipidemia shows that taking freeze-dried beet leaf 2.8 grams daily for 4 weeks in addition to nutritional guidance does not reduce body weight or body mass index (BMI) when compared with nutritional guidance alone (100146). Similarly, a small clinical study in adults with overweight or obesity on a calorie-restricted diet shows that drinking 70 mL of concentrated beetroot juice daily for 14 days does not improve weight loss when compared with controls (111158). However, the size and duration of this study may have been inadequate to detect differences between groups.
• Pregnancy-induced hypertension. It is unclear if oral beetroot juice is beneficial in patients with pregnancy-induced hypertension. Details: A small clinical trial in pregnant patients with hypertension who are at approximately 22-35 weeks gestation shows that taking beetroot juice (James White Drinks Ltd) 70 mL daily for 8 days does not reduce blood pressure when compared with a nitrate-depleted beetroot juice (100151). However, the study was small and designed to investigate the feasibility of using beetroot juice in this population.
• Pulmonary hypertension. It is unclear if oral beetroot juice is beneficial in patients with pulmonary hypertension. Details: A small clinical study shows that taking beetroot juice (Beet-It Sport; James White Drinks Ltd) 70 mL twice daily for 7 days does not improve right ventricular systolic function when compared with nitrate-depleted beetroot juice in patients with pulmonary hypertension (100149). However, this study was small and not adequately powered to detect differences between groups.
• Raynaud syndrome. It is unclear if oral beetroot juice is beneficial in patients with Raynaud syndrome. Details: A small clinical study in patients with Raynaud syndrome undergoing cold sensitivity tests shows that drinking beetroot juice (Beet-It, James White Drinks Ltd) 70 mL daily for 13 days, followed by 140 mL prior to testing, does not reduce pain in the hands or feet, but might improve thermal comfort in the feet, when compared to baseline (103884). The validity of this finding is limited by the lack of a comparator group. More evidence is needed to rate beet for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral German chamomile for allergic rhinitis, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Anxiety. It is unclear if inhaled German chamomile essential oil, as aromatherapy, is beneficial in patients with anxiety. Details: A large clinical study in adults in Iran hospitalized with acute coronary syndrome shows that placing 7 drops of German chamomile essential oil 10% on a cotton ball and inhaling for 12 hours nightly for 2 nights modestly lowers anxiety scores when compared with a control group (114528). The validity of this finding is limited by the potential for inadequate blinding and the short study duration. However, a small clinical study in adults with gastrointestinal, neuroendocrine, and skin cancers receiving intravenous infusion therapy shows that inhaling German chamomile essential oil 3 times daily for 7 days does not reduce self-reported anxiety when compared with a control group (111379). German chamomile has also been studied in combination with other ingredients. A small, open-label study in critically ill children in the pediatric intensive care unit shows that aromatherapy massage with an essential oil 1% blend of lavender, German chamomile, and neroli in grapeseed oil reduces distress, anxiety, and heart rate when compared to baseline (111378). However, the validity of these findings is limited by a lack of blinding and control group. It is unclear if these effects are due to German chamomile, other ingredients, or the combination.
• Atopic dermatitis (eczema). It is unclear if topical German chamomile is beneficial in patients with atopic dermatitis. Details: Clinical research in patients with atopic dermatitis shows that applying a specific cream containing a 2% ethanolic extract of German chamomile flowers (Kamillosan, Asta Medica AG) up to three times daily for up to 4 weeks improves pruritus, erythema, and desquamation when compared with placebo or hydrocortisone 0.5% cream (19707).
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral German chamomile for ADHD, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Burning mouth syndrome. German chamomile has only been evaluated as a mouthwash in combination with flaxseed; its effect when used alone is unclear. Details: Preliminary clinical research in female patients with burning mouth syndrome shows that using a mouthwash containing German chamomile and flaxseed 3-4 times daily for 3 months decreases subjective burning and dry mouth symptoms, increases salivary flow rate, and decreases saliva viscosity when compared with baseline (104807). However, the validity of these results is limited by the lack of a control group and product standardization, as the mouthwash was prepared by each patient from ingredients they purchased.
• Cancer-related anorexia. It is unclear if inhaled German chamomile essential oil, as aromatherapy, is beneficial in patients with cancer-related anorexia. Details: A small clinical study in adults with gastrointestinal, neuroendocrine, and skin cancers receiving intravenous infusion therapy shows that inhaling German chamomile essential oil 3 times daily for 7 days does not increase self-reported appetite when compared with a control group (111379).
• Chemotherapy-induced fatigue. It is unclear if inhaled German chamomile essential oil, as aromatherapy, is beneficial in patients with chemotherapy-induced fatigue. Details: A small clinical study in adults with gastrointestinal, neuroendocrine, and skin cancers receiving intravenous infusion therapy shows that inhaling German chamomile essential oil 3 times daily for 7 days does not reduce self-reported fatigue when compared with a control group (111379).
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if inhaled German chamomile essential oil, as aromatherapy, is beneficial in patients with CINV. Details: A small clinical study in adults treated for gastrointestinal, neuroendocrine, and skin cancers with intravenous infusion therapy shows that inhaling German chamomile essential oil 3 times daily for 7 days does not improve self-reported nausea when compared with a control group. (111379).
• Colic. Oral German chamomile has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical studies in infants with colic show that two multi-ingredient products given orally twice daily for 1-4 weeks reduce crying times when compared with placebo or simethicone 60 mg twice daily. The products studied contained German chamomile 178 mg with fennel and lemon balm (ColiMil, Milte Italia SPA) and German chamomile 9 mg with lemon balm and Lactobacillus acidophilus (ColiMil Plus, Milte Italia SPA) (16735,96278). Other clinical research in infants shows that taking 150 mL of a specific herbal tea preparation (Calma-Bebi, Bonomelli) containing extracts of German chamomile, vervain, licorice, fennel, and lemon balm up to three times daily after each episode of colic for 7 days increases the percentage of infants with relief by 31% when compared with placebo, although there was no effect on the number of night awakenings (19715).
• Common cold. It is unclear if inhaling the steam from a solution of German chamomile in hot water is beneficial in patients with a common cold. Details: Preliminary clinical research shows that inhaling the steam from a solution containing 13-39 mL of German chamomile alcoholic extract (Kneipp Kamillen-Konzentrat, Kneipp Werke) dissolved in 1000 mL of hot water for 10 minutes reduces symptoms when compared to baseline in patients suffering from an uncomplicated common cold (19360).
• Diarrhea. Oral German chamomile has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children aged 6 months to 6 years with acute diarrhea, using a specific combination product (Diarrhoesan, Dr. Loges + Co. GmbH) containing apple pectin and German chamomile extract for 1-3 days reduces stool frequency and improves symptom relief when compared with placebo (19705).
• Dysmenorrhea. Although there has been interest in using oral German chamomile for dysmenorrhea, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Dyspepsia. Oral German chamomile has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Two specific combination products containing German chamomile (Iberogast, Steigerwald Arzneimittelwerk GmbH; STW-5-S, Steigerwald Arzneimittelwerk GmbH), 1 mL three times daily for 4 weeks, seem to improve symptoms of dyspepsia. The combinations include German chamomile plus milk thistle, peppermint leaf, licorice, caraway, celandine, angelica, and lemon balm, with (Iberogast) or without (STW-5-S) clown's mustard plant (19532). A meta-analysis of studies using Iberogast product suggests that taking 1 mL orally three times daily for 4 weeks reduces severity of acid reflux, epigastric pain, cramping, nausea, and vomiting when compared with placebo (13089). Also, using a preparation containing clown's mustard plant, German chamomile, peppermint, caraway, licorice, and lemon balm (STW 5-II, Steigerwald Arzneimittelwerk GmbH), 1 mL three times daily for up to 12 weeks, improves symptoms in 40% more patients than placebo (12724).
• Fibromyalgia. Although there has been interest in using oral German chamomile for fibromyalgia, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Flatulence. It is unclear if oral German chamomile is beneficial in adults with flatulence post-laparoscopic cholecystectomy. Details: A moderate-sized clinical study in adults undergoing laparoscopic cholecystectomy conducted in Iran shows that German chamomile extract 20 drops given once orally 1 hour before surgery mitigates the severity and incidence of flatulence 2 hours postoperatively when compared with placebo (112364). The interpretation of these findings is limited by the use of self-reported outcomes. In addition, providers had influence on who received German chamomile, raising concerns about selection bias.
• Generalized anxiety disorder (GAD). It is unclear if oral German chamomile is beneficial in adults with GAD. Details: Small clinical studies in adults with GAD show that taking German chamomile extract 220-1500 mg daily for 8-26 weeks improves anxiety rating scores but does not reduce the risk of relapse when compared with placebo (19377,111380). Clinical practice guidelines from the World Federation of Societies of Biological Psychiatry and the Canadian Network for Mood and Anxiety Treatments do not currently recommend German chamomile as monotherapy or adjunctive therapy in patients with GAD (110318).
• Gingivitis. Topical German chamomile has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in people with gingivitis shows that using a toothpaste containing German chamomile, sage, myrrh, eucalyptus, calcium carbonate, and sodium monofluorophosphate twice daily for 30 days reduces gingivitis scores when compared with baseline, but not when compared with standard toothpaste (19702).
• Hemorrhoids. Topical German chamomile might improve symptoms after anal surgery for hemorrhoids. Details: Preliminary clinical research in patients with hemorrhoids shows that German chamomile ointment (Kamillosan, Asta Medica AG) applied twice daily for 6 weeks, in combination with band ligation plus anal dilation surgery, improves anal bleeding, itching, burning, and oozing when compared with surgery alone (19714).
• Hyperprolactinemia. Oral German chamomile might lower prolactin levels, but is not likely to work as well as conventional medications. Details: Preliminary clinical research in female patients with idiopathic hyperprolactinemia shows that taking a syrup containing 10% of a German chamomile dried flower extract 5 mL twice daily for 4 weeks produces a significant decline in serum prolactin levels when compared with baseline. However, the decrease is less than that associated with taking cabergoline 0.25 mg twice weekly for 4 weeks. Serum prolactin levels normalized in 96% of patients taking cabergoline, and 72% of patients taking German chamomile (104806).
• Inflammatory bowel disease (IBD). Although there has been interest in using oral German chamomile for IBD, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Insomnia. Oral German chamomile does not seem to be beneficial in patients with primary insomnia. Details: Preliminary clinical research in patients with primary insomnia shows that taking German chamomile 270 mg twice daily for 28 days does not improve total sleep time, sleep efficiency, sleep latency, sleep quality, waking after sleep onset, or number of awakenings when compared with placebo (19716).
• Leukemia. It is unclear if oral German chamomile is beneficial in children with leukemia. Details: One small clinical study in children aged 2-18 years with acute lymphoblastic leukemia suggests that taking German chamomile flower extract 125 mg in 2.5 mL syrup daily for 30 days during induction chemotherapy is associated with a more rapid recovery in absolute neutrophil counts, but not white blood cell counts, when compared with placebo (103180). However, statistical methods used are unclear, and it is not known if German chamomile altered the effectiveness of chemotherapy.
• Mastalgia. Preliminary research suggests that German chamomile might be effective for reducing the pain of premenstrual mastalgia. Details: Preliminary clinical research in patients with cyclic (premenstrual) mastalgia shows that taking 5 drops of German chamomile extract orally three times daily for 2 months reduces the severity of mastalgia when compared with placebo (104811).
• Nocturnal enuresis. Topical German chamomile has only been evaluated in combination with almond oil; its effect when used alone is unclear. Details: Preliminary clinical research in children with enuresis shows that applying 6 drops of almond oil infused with German chamomile flower to the perineal and suprapubic areas nightly for 6 weeks reduces the frequency of enuresis by about 3 episodes per week when compared with placebo (98621).
• Oral mucositis. Small clinical studies suggest that oral rinses containing German chamomile might help to prevent or treat oral mucositis associated with radiation therapy, chemotherapy, or hematopoietic stem cell transplantation (HSCT). Details: Clinical research shows that using an oral rinse containing German chamomile extract (Kamillosan Liquidum, Asta Media AG) three times daily might help prevent or treat mucositis associated with radiation therapy and several chemotherapy drugs, but not 5-fluorouracil (6655,6656). Other clinical research in patients undergoing HSCT shows that using German chamomile 1% oral rinse twice daily along with standard care reduces the risk of oral mucositis by 67% when compared with standard care alone. However, 0.5% and 2% rinses did not decrease the risk, suggesting that the study may have been underpowered to detect differences (99853). German chamomile has also been studied in combination with other herbal ingredients. One clinical study shows that using an oral rinse containing 1% peppermint oil and 1% German chamomile extract, diluted in water, three times daily starting 1 week before HSCT might help to reduce the severity and duration of oral mucositis induced by high-dose pre-HSCT chemotherapy when compared with placebo. However, the oral rinse does not prevent oral mucositis or reduce the duration of hospitalization when compared with placebo (95622). Another small clinical study in adults with head and neck cancer receiving radiotherapy shows that rinsing with 5 mL of a mouthwash containing German chamomile, peppermint oil, aloe vera, and honey 3 times daily for 60 seconds for 6 weeks starting on the first day of radiotherapy reduces oral mucositis incidence, severity, and pain compared with chlorhexidine and placebo (111291). It is unclear if these findings are due to German chamomile, other ingredients, or the combination.
• Peptic ulcers. Although there has been interest in using oral German chamomile for peptic ulcers, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Periodontitis. German chamomile 1% mouthwash may be similarly effective to chlorhexidine 0.12% mouthwash. Details: Preliminary clinical research shows that using 15 mL of a 1% German chamomile flower mouthwash twice daily for 30 days reduces symptoms and severity of periodontitis by a similar amount when compared with chlorhexidine 0.12% mouthwash (104808).
• Pressure ulcers. Although there has been interest in using oral German chamomile for pressure ulcers, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Radiation dermatitis. It is unclear if topical German chamomile is beneficial for preventing dermatitis caused by radiotherapy. Details: A small clinical study in adults with head and neck cancer undergoing radiotherapy who developed dry desquamation shows that applying a German chamomile 2.5% compress, 20 minutes 3 times daily, results in complete or partial regression of the dry desquamation in 65% and 35% of patients, respectively, and delays the development of moist desquamation by 5-10 days (111376). The validity of these findings is limited by a lack of a comparator group. Another small clinical study in females with breast cancer shows that using a lotion containing a microencapsulated German chamomile extract 0.2%, applied daily after radiation therapy, starting on the first day and continued until the end of treatment, does not improve the incidence or time to onset of any grade of radiation dermatitis on day 35, although it may delay the time to onset of grades 2 or greater, when compared with an identical lotion vehicle control. German chamomile may modestly improve the rate of skin recovery in those with more severe dermatitis over the 15 days following therapy completion (108993). However, due to the small size of the study and short follow-up duration, the validity of these findings is unclear.
• Rhinosinusitis. Using German chamomile nose drops might improve symptoms of rhinosinusitis. Details: Preliminary clinical research in patients with rhinosinusitis shows that using 3 drops of an ethanolic German chamomile extract in each nostril three times daily for 3 weeks reduces symptom scores and improves quality of life when compared with a sesame seed oil placebo (104810).
• Sexual dysfunction. A 5% German chamomile vaginal gel may have similar efficacy to conjugated estrogen vaginal cream in postmenopausal patients. Details: Preliminary clinical research in postmenopausal patients with sexual dysfunction shows that using a 5% German chamomile vaginal gel, 1 gram nightly for 2 weeks then twice weekly for 10 weeks, decreases dyspareunia and increases sexual satisfaction to a similar extent as conjugated estrogen vaginal cream used in the same dosage (104809).
• Vaginitis. Although there has been interest in using oral German chamomile for vaginitis, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Venous leg ulcers. Although there has been interest in using oral German chamomile for venous leg ulcers, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Wound healing. It is unclear if topical German chamomile is beneficial for wound healing. Details: Preliminary clinical research in adults undergoing abrasive tattoo removal shows that applying a topical German chamomile product (Kamille Spitzner, W. Spitzner Arzneimittelfabrik GmbH) three times daily for 14 days reduces wound size by day 4 of treatment when compared with placebo (19718). However, no significant differences in wound healing were observed after 18 days. More information is needed to rate German chamomile for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). It is unclear if oral hemp seed oil is beneficial in patients with eczema. Details: A small preliminary clinical trial in patients with eczema shows that taking hemp seed oil 30 mL daily for 8 weeks improves skin dryness, itchiness, and use of dermal medication when compared with baseline, but not when compared with an olive oil control (101125).
• Constipation. Oral hemp seed has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with functional constipation shows that taking a proprietary Chinese herbal medicine (Hemp Seed Pill) containing hemp seed, rhubarb root, peony root, apricot kernel, bitter orange fruit, and magnolia bark twice daily for 8 weeks results in a response rate to 43%, compared with 8% in those taking placebo. The response rate was defined as an increase of at least 1 complete spontaneous bowel movement per week. This combination product also improved the responder rate in the 2 weeks after treatment, as well as the overall use of rescue therapy, when compared with placebo (101127). Data from this study pooled with data from another larger study in adults with functional constipation shows that this same product increases the likelihood of complete response, defined as at least 3 complete spontaneous bowel movements per week or an increase over baseline of at least 1 weekly, by 1.43 times when compared with placebo. Complete spontaneous bowel movements per week also increased by 1 when compared with placebo (107319). It is unclear if these effects are due to hemp seed, other ingredients, or the combination.
• Dysmenorrhea. Although there is interest in using oral hemp for dysmenorrhea, there is insufficient reliable information about the clinical effects of oral hemp for this condition.
• Familial hypercholesterolemia. It is unclear if oral hemp seed oil is beneficial in children with this condition. Details: A small preliminary clinical trial shows that taking hemp seed oil (AlfaLife, Freia Farmaceutici Srl) 3 grams daily for 8 weeks does not improve levels of total or low-density lipoprotein (LDL) cholesterol when compared with no treatment in hyperlipidemic children aged 6-16 years who are also following a low-fat diet with high fruit and vegetable intake (101144).
• Joint pain. Although there is interest in using oral hemp for joint pain, there is insufficient reliable information about the clinical effects of oral hemp for this condition.
• Multiple sclerosis (MS). Oral hemp seed has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with relapsing-remitting MS shows that taking a combination of hemp seed oil 5.4-6.3 grams and evening primrose oil three times daily for 6 months seems to improve disability scores and relapse rate when compared to baseline. However, the control group in this study ingested olive oil and also experienced notable improvements in disability and relapse rates (88183). This study is limited due to high dropout rate and because there was no statistical comparison between treatment and control groups.
• Obesity. It is unclear if an oral cannabidiol-rich hemp oil extract helps to improve weight loss. Details: A small clinical study in healthy overweight adults shows that taking a specific hemp oil extract (PlusCBD Extra Strength Hemp Extract, CV Sciences) as 60 mg, providing 15 mg cannabidiol, daily for 6 weeks, does not reduce weight or body mass index when compared with placebo (103805). The validity of this study is limited due to its exploratory nature and lack of control for voluntary dietary changes.
• Osteoarthritis. It is unclear if oral hemp seed is beneficial in patients with osteoarthritis. Details: A clinical study in 18 older adults with osteoarthritis undergoing in-hospital rehabilitation following knee or hip arthroplasty shows that consuming pasta enriched with hemp seed flour for 6 weeks improves pain scores by about 3 points, compared with only 1 point in those consuming a regular pasta control (107320).
• Psychological well-being. Although there is interest in using oral hemp for psychological well-being, there is insufficient reliable information about the clinical effects of oral hemp for this condition. More evidence is needed to rate hemp for these uses.

(Read more about HEMP)

POSSIBLY EFFECTIVE

• Dry mouth. Most clinical research shows that topical malic acid, used as either a mouth spray or a lozenge for up to 2 weeks, improves symptoms in patients with dry mouth from various causes. Details: A meta-analysis of five small clinical studies in patients with dry mouth from various causes shows that using a mouth spray containing malic acid 1%, with or without xylitol and fluoride, up to 8 times daily for 2 weeks improves dry mouth symptoms and increases salivary flow when compared with placebo or xylitol and fluoride alone (107916). Dry mouth in the evaluated patients was associated with antihypertensive therapy (92211), antidepressant therapy (92213), aging (95565), graft-versus-host disease (101174), and Sjogren syndrome (104778). Malic acid-containing products evaluated for dry mouth include Xeros Dentaid spray (92211,92213,95565), Xeros Dentaid tablets (104778), and SalivAktive (101174). Additionally, a small clinical study in patients with dry mouth due to type 2 diabetes shows that using malic acid 1% mouth spray on-demand for 2 weeks modestly increases salivary flow and improves patient-reported xerostomia scores at the 2-week follow-up, but not at the 1-month follow up, when compared with placebo (111743). Despite most studies showing consistent and positive results, one small clinical study in patients with idiopathic or drug-induced dry mouth failed to show significant improvement with Xeros Dentaid spray when compared with placebo. However, the malic acid spray performed similarly to betaine-based mouthwash and the study was likely underpowered to detect differences between groups (107917).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Topical malic acid has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: An open-label, non-randomized clinical study in patients with mild-to-moderate acne shows that applying a specific cream (Hyseac AHA cream, Uriage) containing malic acid and arginine glycolate twice daily for 60 days, alone or in combination with prescribed pharmacological treatment, improves acne severity in about 64% of patients when compared to baseline. Pharmacological treatment consisted primarily of antibiotics, but also included retinoids and benzyl peroxide (92207). These findings are limited by the lack of a comparator group. Also, it is unclear if these findings are due to malic acid, arginine glycolate, or the combination.
• Actinic keratoses. Although there has been interest in using topical malic acid for actinic keratoses, there is insufficient reliable information about the clinical effects of malic acid for this purpose.
• Fatigue. Although there has been interest in using oral malic acid for fatigue, there is insufficient reliable information about the clinical effects of malic acid for this purpose.
• Fibromyalgia. Oral malic acid has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with fibromyalgia shows that taking a specific product (Super Malic) containing malic acid 1200 mg and magnesium hydroxide 300 mg twice daily for 6 months reduces pain and tenderness when compared to baseline. However, taking malic acid 600 mg with magnesium hydroxide 150 mg twice daily for 1 month does not reduce pain and tenderness when compared with placebo (3262). The validity of the findings in the follow-on, open-label, 6-month phase of the study is limited by a lack of blinding and placebo control. Also, it is unclear if these findings are due to malic acid, magnesium, or the combination.
• Gastroesophageal reflux disease (GERD). Oral malic acid has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in patients with GERD shows that using a specific lozenge containing malic acid 25.58 mg, xylitol 422 mg, and fluoride 0.58 mg (Xeros Dentaid tablets, Dentaid) three times daily in combination with omeprazole 40 mg daily for 6 months may improve saliva buffering capacity and some symptoms of GERD when compared with omeprazole alone (104757). It is unclear if these findings are due to malic acid, other ingredients, or the combination.
• Psoriasis. Although there has been interest in using topical malic acid for psoriasis, there is insufficient reliable information about the clinical effects of malic acid for this purpose.
• Warts. Although there has been interest in using topical malic acid for warts, there is insufficient reliable information about the clinical effects of malic acid for this purpose.
• Wrinkled skin. Although there has been interest in using topical malic acid for wrinkled skin, there is insufficient reliable information about the clinical effects of malic acid for this purpose. More evidence is needed to rate malic acid for these uses.

(Read more about MALIC ACID)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Although there is interest in using oral fermented papaya for aging skin, there is insufficient reliable information about the clinical effects of papaya for this purpose.
• Androgenic alopecia. Papaya has only been evaluated in combination with other ingredients for androgenic alopecia; its effect when used alone is unclear. Details: A clinical study in adults with androgenic and diffuse alopecia shows that applying fermented papaya 2% hair lotion also containing fermented mangosteen and caffeine on the scalp daily plus fermented papaya 0.5% shampoo also containing fermented mangosteen on the scalp 3 times weekly for 14 weeks shows improvement in hair loss intensity and the quality of hair shaft compared to baseline (111719). It is unclear if the effect is due to the fermented papaya, other ingredients, or the combination.
• Colorectal cancer. It is unclear if oral papaya fruit prevents colorectal cancer. Details: One small observational study in adults living in Thailand has found that papaya fruit consumption is associated with a 42% lower odds of developing colorectal cancer (67941).
• Dengue fever. Small clinical studies suggest that oral papaya leaf extract might increase platelet counts in patients with dengue fever. Details: A meta-analysis of mostly small clinical studies in adults with dengue fever shows that taking papaya leaf extract reduces the duration of hospital stay by about 2 days and improves mean platelet count over the next five days by about 35 x 10⁹ when compared with standard treatment. The most common dosing ranged from 500 mg to 3300 mg daily for five days in divided doses (102799). This finding is limited by imprecision and high risk of bias. One additional small clinical study in patients with severe thrombocytopenia due to dengue fever shows that taking a papaya leaf extract (Caripill, Micro Labs) 1100 mg three times daily for 5 days increases platelet counts by a greater amount through day 3 when compared with placebo, and reduces the median time to platelet recovery by one day (102800).
• Diabetes. It is unclear if oral fermented papaya improves glycemic control in patients with diabetes. Details: A small clinical study in patients with type 2 diabetes shows that consuming fermented papaya fruit 3 grams once daily for 2 months reduces fasting and postprandial blood glucose levels by 13% and 10%, respectively, when compared to baseline (67902). The validity of this finding is limited by the lack of a comparator group.
• Gallbladder cancer. It is unclear if oral fermented papaya prevents gallbladder cancer. Details: One small observational study in adults living in Thailand has found that eating papaya fruit is associated with a 66% lower odds of developing gallbladder cancer (67871).
• Gingivitis. It is unclear if using toothpaste and/or mouthwash containing fermented papaya leaf extract improves symptoms of gingivitis. Details: Preliminary clinical research in adults with good oral hygiene shows that brushing teeth twice daily with a toothpaste containing papaya leaf extract for 4 weeks, with or without the use of a papaya leaf extract-containing mouthwash, decreases gingival bleeding when compared to baseline. However, using this toothpaste with or without the mouthwash is no better than using a sodium lauryl sulfate (SLS)-free, enzyme-containing toothpaste, with or without an essential oil mouthwash (99861).
• Human papillomavirus (HPV). It is unclear if oral papaya fruit prevents persistent HPV infection. Details: A small population study in females infected with HPV has found that consuming papaya fruit at least once weekly is associated with 70% lower odds of persistent HPV infection when compared with never eating papaya fruit (67881).
• Intestinal parasite infection. Although there is interest in using oral papaya for intestinal parasite infection, there is insufficient reliable information about the clinical effects of papaya for this condition.
• Periodontitis. It is unclear if applying fermented papaya gel into gingival pockets is beneficial for periodontitis. Details: One small open-label clinical study in adults with moderate to severe periodontitis shows that, when used in addition to standard treatment, applying fermented papaya gel (Carica Co.) 7 grams into intragingival pockets for 15 minutes daily for 10 days seems to improve bleeding, plaque, and gingivitis after 7-45 days when compared with standard treatment alone (93090). The validity of this finding is limited by the lack of blinding.
• Thrombocytopenia. Although there is interest in using oral papaya leaf extract for immune thrombocytopenic purpura (ITP), there is insufficient reliable information about the clinical effects of papaya for this condition.
• Wound healing. It is unclear if topical papaya fruit gel is beneficial for wound healing. Details: A small open-label clinical study in patients with post-caesarean section wound gape shows that applying a wound dressing containing partially ripe papaya fruit 200 grams to the edges of a gaped wound for 48 hours, and re-applying as needed, seems to modestly speed up the development of granulation tissue and reduce the duration of hospitalization when compared with using hydrogen peroxide dressings, changed daily (93091). The validity of this finding is limited because the control treatment with hydrogen peroxide may cause skin damage and slow wound healing. More evidence is needed to rate papaya for these uses.

(Read more about PAPAYA)

LIKELY EFFECTIVE

• Constipation. Taking senna orally is effective for the short-term treatment of constipation. Details: Senna is an FDA-approved nonprescription drug marketed for the short-term treatment of constipation in adults and children ages 2 years and older (15429,15433,15436,15441,15442,74545,74607,74609,74613,74615). Senna usually produces a laxative effect 6-10 hours after oral administration (15429,96559). However, in children ages 3-15 years, mineral oil and lactulose might be more effective (15434,15435). Taking senna with psyllium is also effective for the short-term treatment of constipation (8424,74593), with the combination increasing stool moisture to a greater degree than psyllium alone (8424). In patients with opioid or loperamide-induced constipation, taking senna appears to be as effective as lactulose, psyllium, and docusate for relieving constipation (15432,74586,74644,74650). Some population research has found that senna may be more effective than docusate, polyethylene glycol, and lactulose for preventing problematic constipation, the need for an enema, and abdominal imaging in pediatric cancer patients receiving opioids (92710). Senna also seems to be beneficial in chronic constipation. Clinical guidelines published by the American Gastroenterology Association and American College of Gastroenterology in 2023 give a conditional recommendation suggesting the use of senna over managing chronic idiopathic constipation without senna based on low-quality of evidence conducted over 4 weeks (112859). In geriatric patients, senna plus psyllium is more effective than lactulose for treating chronic constipation (15438,15439,15440). Also, a small study in middle-aged adults with chronic idiopathic constipation shows that taking senna (ALOSENN granules) 500 mg twice daily for 4 weeks seems to be similarly effective to taking magnesium oxide 500 mg three times daily (105959).

POSSIBLY EFFECTIVE

• Bowel preparation. Taking oral senna might be effective for bowel cleansing before colonoscopy. Details: A meta-analysis of 10 clinical trials in adults shows that taking senna alone or with other bowel preparations does not improve bowel cleansing before elective colonoscopy when compared with non-senna bowel preparations. However, in a subgroup analysis of 3 clinical studies, taking senna solution alone is about 2.5 times more likely to result in a clean bowel when compared with polyethylene glycol alone (112893). The interpretation of these findings is limited by varied senna dosages and regimens. Additionally, 2 clinical studies that were not included in this meta-analysis show that senna is as effective or more effective than polyethylene glycol for improving bowel cleanse quality (15431,40088). Conversely, other studies show that polyethylene glycol is superior to senna (40086,74587,74606,74636). It is also unclear if taking senna with polyethylene glycol improves bowel cleansing when compared with polyethylene glycol alone (74583,74585). Some clinical studies show that senna is as effective as castor oil and bisacodyl for bowel cleansing (74548,74603,74624). Although taking senna alone is less effective than sodium phosphate (15431,74567,74570,74653,92712), some evidence suggests that taking a combination of senna, sodium picosulfate, and polyethylene glycol is more effective than sodium phosphate for bowel cleansing prior to colonoscopy (74538). Limited research has also assessed the benefit of adding senna to a preparation regimen for small bowel capsule endoscopy; however, it is unclear whether the addition of senna improves endoscopy outcomes when compared with the preparation regimen alone (96557). There is insufficient reliable information available about the effectiveness of senna for its other uses.

(Read more about SENNA)

LIKELY EFFECTIVE

• Cystic fibrosis. Long-term nebulized hypertonic sodium chloride improves lung function and reduces pulmonary exacerbations in patients with cystic fibrosis. Details: Meta-analyses of clinical research in adults with cystic fibrosis show that, when taken along with a bronchodilator and other standard therapies, nebulized hypertonic sodium chloride in concentrations of 3% to 7%, up to 10 mL twice daily for 4 weeks, increases forced expiratory volume at one second (FEV1) when compared with isotonic saline (sodium chloride 0.9%) (26230,26230). This benefit was not seen at 48 weeks. Other clinical research in adults with cystic fibrosis shows that inhaling sodium chloride 7%, 4 mL twice daily for 48 weeks, does not improve FEV1 when compared with isotonic saline. However, chronic treatment with hypertonic saline does reduce the number of pulmonary exacerbations and increase the number of patients without pulmonary exacerbations when compared with isotonic saline (29402). It is not clear if this benefit occurs in children with cystic fibrosis. The Pulmonary Clinical Practice Guidelines Committee of the Cystic Fibrosis Foundation recommends that individuals with cystic fibrosis aged 6 years or older use nebulized hypertonic saline long-term to improve lung function, reduce the number of exacerbations, and improve quality of life (29403).

POSSIBLY EFFECTIVE

• Amphotericin B nephrotoxicity. Oral sodium chloride seems to prevent nephrotoxicity associated with use of amphotericin B. Details: Clinical research shows that administering oral or intravenous sodium chloride 150 mEq daily during treatment with amphotericin B can attenuate the rise in serum creatinine levels and preserve renal function when compared to treatment with amphotericin B alone (26226).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bipolar disorder. It is unclear if oral sodium is beneficial in preventing lithium level fluctuations in patients with bipolar disorder. Details: A moderate-sized open-label clinical study in adults with type I bipolar disorder receiving lithium carbonate shows that taking sodium chloride 1 gram daily for 12 weeks along with dietary salt restriction of 1 gram daily reduces the percentage of patients with lithium level fluctuations above 0.8 mEq/L, but does not significantly affect serum sodium, potassium, aldosterone, or creatinine levels when compared with controls who were not salt restricted, but were advised not to consume additional salt at the table (112909). However, the interpretation of these findings is limited by missing data in both groups.
• Canker sores. Although there is interest in using topical sodium chloride for canker sores, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Congestive heart failure. It is unclear if oral sodium is beneficial in patients with acute decompensated heart failure requiring decongestive therapy with diuretics. Details: A moderate-sized clinical study in adults hospitalized with acute decompensated heart failure requiring high-dose intravenous furosemide shows that taking sodium chloride 2 grams three times daily for up to 96 hours does not affect patient weight or serum creatinine levels when compared with placebo (112911). However, the clinical relevance of this study is unclear and it may have been inadequately powered to detect a difference between groups.
• Conjunctivitis. Although there is interest in using ophthalmic sodium chloride for conjunctivitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Hyponatremia. Although there is interest in using oral sodium chloride for hyponatremia, there is insufficient reliable information about the clinical effects of oral sodium chloride for this condition.
• Pharyngitis. Although there is interest in using topical sodium chloride for pharyngitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Prematurity. It is unclear if oral sodium is beneficial for premature infants. Details: Preliminary clinical research in infants born at less than 32 weeks' gestation shows that adding sodium 4 mEq/kg daily to enteral feedings, starting from the 7th day after birth and continuing through the 35th day, reduces the risk of developing hyponatremia and improves weight gain when compared with adding water (98180). A small, open-label clinical study in newborns less than 35 weeks gestation shows that high sodium intake, defined as an average of 0.25% sodium in maintenance fluids, for 48 hours on day 2 and 3 after birth results in less weight loss within the first 72 hours of life when compared with control, but does not improve mortality, length of hospital stay, or complications from prematurity (112908). However, interpretation of these findings is limited by varied concentrations of sodium as an intervention. More evidence is needed to rate sodium for these uses.

(Read more about SODIUM)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. It is unclear if oral stevia is beneficial in patients with diabetes; the available research is conflicting. Details: A small single-dose study shows that taking stevia leaf extract 1000 mg, standardized to contain 91% stevioside, along with a meal reduces postprandial glucose levels by 18% in adults with type 2 diabetes when compared with a starch control (11812). However, clinical research in patients with type 1 or type 2 diabetes shows that taking stevioside 250 mg three times daily for 3 months does not affect blood glucose levels or glycated hemoglobin (HbA1C) when compared with baseline (16705). Also, a small clinical study in patients with diabetes shows that drinking 200 mL of black tea, sweetened with stevia extract 2%, three times daily for 8 weeks does not affect glycemic indices when compared with drinking tea sweetened with sucralose (103695).
• Hypertension. It is unclear if oral stevia is beneficial in patients with hypertension; the available research is conflicting. Details: Some clinical research in patients with mild to moderate hypertension shows that taking stevioside, a constituent of stevia, 750-1500 mg in three divided doses daily reduces systolic blood pressure by 10-14 mmHg and diastolic blood pressure by 6-14 mmHg within one week to three months of treatment initiation and continuing for up to 2 years (11809,11810). However, other clinical research in patients with mild hypertension shows that taking stevioside in doses up to 15 mg/kg daily does not significantly reduce blood pressure (16706).
• Obesity. It is unclear if oral stevia is beneficial in patients with obesity; the available research is conflicting. Details: Although a small clinical study in healthy adults shows that drinking water with stevia (Truvia) 245 ppm as a single dose reduces appetite and energy intake when compared with drinking water alone (103697), other small, single-dose studies have shown no effect of stevia 15.3 mg or 1 gram as a single dose on satiety, energy intake, or fullness when compared with either water alone or a non-nutritive sweetener (103696,110124). A small clinical study in healthy adults shows that taking an aqueous stevia leaf extract (SweetLeaf) twice daily for 12 weeks does not affect body weight, compared with an increase in weight in the control group. This suggests that stevia extract may have attenuated weight gain in this study (106458). More evidence is needed to rate stevia for these uses.

(Read more about STEVIA)

LIKELY SAFE ...when used in amounts commonly found in foods.

POSSIBLY SAFE ...when used orally and appropriately for medicinal purposes, short term. Beetroot juice has been safely used in clinical trials in doses of up to 500 mL daily for up to 7 days and a beetroot-based nutritional gel has been used safely in doses of up to 100 grams daily for 8 days (94461,94462,94464,100149,100152,100153).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of beets used medicinally during pregnancy and breast-feeding.

(Read more about BEET)

LIKELY SAFE ...when used orally in amounts commonly found in foods. German chamomile has Generally Recognized as Safe (GRAS) status in the US (4912,110318).

POSSIBLY SAFE ...when used orally, for medicinal purposes, short-term. German chamomile has been used with apparent safety at doses of up to 1500 mg daily for up to 26 weeks (6655,12724,12729,13089,19377,19716,104806,111380). ...when applied topically. A lotion containing 0.2% microencapsulated German chamomile extract has been applied to the skin with apparent safety for up to 35 days (108993). ...when used topically as an oral rinse (99853).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Preliminary clinical research suggests that several multi-ingredient products containing German chamomile are safe in infants when used for up to 4 weeks (16735,19705,19715,96278). ...when used topically and appropriately, short-term. Six drops of oil infused with German chamomile flower has been applied nightly with apparent safety for up to 6 weeks in children 6-18 years old (98621).

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

(Read more about GERMAN CHAMOMILE)

LIKELY SAFE ...when hemp seed, hemp protein, and hemp seed oil are used orally in food amounts. Hulled hemp seed, hemp seed protein powder, and hemp seed oil are generally recognized as safe (GRAS) in the US (100531).

POSSIBLY SAFE ...when hemp seed oil is used orally and appropriately as medicine, short-term. Hemp seed oil in doses of 2-6.3 grams daily has been safely used for 3-6 months (88183,16791,101145). Hemp seed oil in doses of 30 mL (27.6 grams) daily has been used safely for 2 months (101125). There is insufficient reliable evidence available about the safety of hemp oil, flowers, or leaves.

CHILDREN:
There is insufficient reliable information available about the safety of hemp in children. Adverse effects have been noted in case reports, but details related to specific hemp products are limited (101153,110287).

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

(Read more about HEMP)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Malic acid has Generally Recognized as Safe (GRAS) status in the United States. Allowed maximum levels of malic acid in foods are as follows: 3.4% for nonalcoholic beverages; 3% for chewing gum; 0.8% for gelatins, puddings, and fillings; 6.9% for hard candy; 2.6% for jams and jellies; 3.5% for processed fruits and fruit juices; 3% for soft candy; and 0.7% for all other food categories (26969,95594).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Malic acid 1200 mg twice daily has been used with apparent safety for up to 6 months (3262). ...when used topically on oral mucosal surfaces. Specific malic acid combination products (Xeros Dentaid, Dentaid) have been used with apparent safety in spray and lozenge formulations for up to 6 months (92211,92213,95565,104757,104778). There is insufficient reliable information available about the safety of malic acid when used topically on the skin. Historically, malic acid has been used with apparent safety in cosmetics as a pH adjuster or fragrance ingredient, and at concentrations below 2% when used in shampoo, hair styling products, or sun protection products (26868,95595,111742).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (26969,95594). There is insufficient reliable information available about the safety of using malic acid in medicinal amounts during pregnancy or lactation.

(Read more about MALIC ACID)

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

POSSIBLY SAFE ...when the leaf extract is used orally and appropriately in medicinal amounts, short term. The leaf extract has been used with apparent safety in doses of up to 3300 mg daily for up to 5 days (102799,102800). ...when the ripe fruit is used topically and appropriately, short term. The fruit has been applied with apparent safety to the gingiva or skin for up to 10 days (93090,93091).

POSSIBLY UNSAFE ...when the unripe fruit containing papaya latex and raw papain is used orally. Raw papain has been reported to cause esophageal perforation (6,93083). ...when papaya latex is used topically. Papaya latex, which contains raw papain, is a severe irritant and vesicant (6).

PREGNANCY: LIKELY SAFE
when the ripe fruit is consumed in amounts commonly found in foods.

PREGNANCY: POSSIBLY UNSAFE
when the unripe fruit containing papaya latex is used orally; avoid using. There is some concern that crude papain, a constituent of papaya latex, is teratogenic and embryotoxic (6); however, this might be due to extraneous substances rather than papain (11). Some evidence also suggests that high doses of papaya seed extract have abortifacient activity and can adversely affect fetal development (67870). Theoretically, eating large amounts of papaya seeds may have similar effects.

LACTATION: LIKELY SAFE
when the ripe fruit is consumed in amounts commonly found in foods. There is insufficient reliable information available about the safety of using papaya medicinally; avoid using.

(Read more about PAPAYA)

LIKELY SAFE ...when used orally and appropriately, short-term. Senna is an FDA-approved nonprescription drug (8424,15429,15431,15442,40086,40088,74535,74545,74548,74562)(74567,74570,74583,74585,74586,74587,74593,74603,74606,74607)(74609,74613,74615,74624,74636,74639,74644,74650,74653,92711)(92712).

POSSIBLY UNSAFE ...when used orally long-term or in high doses. Long-term, frequent use, or use of high doses has been linked to serious side effects including laxative dependence and liver toxicity (13057,13095).

CHILDREN: LIKELY SAFE
when used orally and appropriately, short-term. Senna is an FDA-approved nonprescription drug for use in children 2 years and older. (15429,15434,15435).

CHILDREN: POSSIBLY UNSAFE
when used orally long-term or in high doses. Long-term, frequent use, or use of high doses has been linked to serious side effects including laxative dependence and liver toxicity (13057,13095,105956).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term (15429,24480). POSSIBLY UNSAFE...when used orally long-term or in high doses. Long-term, frequent use, or use of high doses has been linked to serious side effects including laxative dependence and liver toxicity (13057,13095).

LACTATION: POSSIBLY SAFE
when used orally and appropriately, short term. Although small amounts of constituents of senna cross into breast milk, senna has been taken while breast-feeding with apparent safety. Senna does not cause changes in the frequency or consistency of infants' stools. (6026,15429,15436,15437,24482,24484,24485,24486,24487,74545).

(Read more about SENNA)

LIKELY SAFE ...when used orally and appropriately. Sodium is safe in amounts that do not exceed the Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams daily (100310). Higher doses can be safely used therapeutically with appropriate medical monitoring (26226,26227).

POSSIBLY UNSAFE ...when used orally in high doses. Tell patients to avoid exceeding the CDRR intake level of 2.3 grams daily (100310). Higher intake can cause hypertension and increase the risk of cardiovascular disease (26229,98176,98177,98178,98181,98183,98184,100310,109395,109396,109398,109399). There is insufficient reliable information available about the safety of sodium when used topically.

CHILDREN: LIKELY SAFE
when used orally and appropriately (26229,100310). Sodium is safe in amounts that do not exceed the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310).

CHILDREN: POSSIBLY UNSAFE
when used orally in high doses. Tell patients to avoid prolonged use of doses exceeding the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310). Higher intake can cause hypertension (26229).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Sodium is safe in amounts that do not exceed the CDRR intake level of 2.3 grams daily (100310).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in higher doses. Higher intake can cause hypertension (100310). Also, both the highest and the lowest pre-pregnancy sodium quintile intakes are associated with an increased risk of hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, and the delivery of small for gestational age (SGA) infants when compared to the middle intake quintile (106264).

(Read more about SODIUM)

LIKELY SAFE ...when certain stevia constituents, including stevioside and rebaudiosides A, D, and M, are used orally as sweeteners in foods. These constituents have generally recognized as safe (GRAS) status in the US for this purpose (16699,16700,16702,16705,16706,108049). The stevia constituent stevioside has been safely used in doses of up to 1500 mg daily for 2 years (11809,11810,11811). There is insufficient reliable information available about the safety of whole stevia or stevia extracts when used orally. The European Food Safety Authority (EFSA) has determined that the acceptable intake of steviol glycosides is 4 mg/kg daily (106456); however, it is unclear how this relates to the use of whole stevia or stevia extract.

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

(Read more about STEVIA)

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, beet might decrease the levels and clinical effects of CYP1A2 substrates.  Details In vitro research suggests that beet induces CYP1A2 enzymes (111404).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, beet might increase the levels of CYP3A4 substrates.  Details In vitro research suggests that betanin, the major pigment in beet, competitively inhibits CYP3A4 in a dose-dependent manner similarly to strong CYP3A4 inhibitor ketoconazole (113425).

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CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, German chamomile might have additive effects when used with CNS depressants.  Details German chamomile has mild sedative effects. Theoretically, concomitant use with drugs with sedative properties can cause additive effects and side effects (9765,12725,19719).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, large amounts of German chamomile might reduce the effectiveness of oral contraceptives.  Details In vitro, German chamomile has demonstrated antiestrogenic activity (12728). Theoretically, concomitant use of large amounts of German chamomile might interfere with contraceptive drugs through competition for estrogen receptors.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, German chamomile might inhibit CYP1A2 and increase levels of drugs metabolized by these enzymes.  Details In vitro and animal research shows that German chamomile might inhibit CYP1A2 (12734,19720). So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP1A2 in patients taking German chamomile.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, German chamomile might inhibit CYP2C9 and increase levels of drugs metabolized by these enzymes.  Details In vitro evidence shows that German chamomile might inhibit CYP2C9 (19720). So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2C9 in patients taking German chamomile.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, German chamomile might inhibit CYP2D6 and increase levels of drugs metabolized by these enzymes.  Details In vitro evidence shows that German chamomile might inhibit CYP2D6 (19720). So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2D6 in patients taking German chamomile.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, German chamomile might inhibit CYP3A4 and increase levels of drugs metabolized by these enzymes.  Details In vitro evidence shows that German chamomile might inhibit CYP3A4 (6450,19720). So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP3A4 in patients taking German chamomile.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, large amounts of German chamomile might reduce the effectiveness of estrogens.  Details In vitro, German chamomile has demonstrated antiestrogenic activity (12728). Theoretically, large amounts of German chamomile might interfere with hormone replacement therapy through competition for estrogen receptors.

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, large amounts of German chamomile might interfere with the activity of tamoxifen.  Details In vitro, German chamomile has demonstrated antiestrogenic activity (12728).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D German chamomile might increase the effects of warfarin and increase the risk of bleeding.  Details In one case, a 70-year-old female taking warfarin developed retroperitoneal hematoma and bilateral recti muscle bleeding along with an INR of 7.9 following ingestion of German chamomile tea 4-5 cups daily and use of a topical chamomile-based lotion applied 4-5 times daily (14309).

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ACE INHIBITORS (ACEIs) Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, consuming hemp seed protein isolate with ACE inhibitors might have additive effects and increase the risk of hypotension.  Details Hemp seed protein hydrolysate has shown ACE inhibitor-like effects in a hypertensive animal model (101136). However, hempseed oil consumption does not seem to reduce blood pressure in humans (101144). Until more is known, monitor blood pressure and potassium levels.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, hemp seed might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs.  Details In animal research, hemp seed at 5% of the diet inhibits platelet aggregation in vitro (101137). However, in human research, taking hemp seed oil 2 grams daily for 12 weeks does not inhibit the aggregation of platelets in vitro (16791).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, hemp seed protein may have additive effects with antihypertensive drugs.  Details In a hypertensive animal model, hemp seed protein hydrolysate reduced systolic blood pressure by a mechanism possibly involving the inhibition of renin and angiotensin converting enzyme (ACE) activities. However, there was no effect of hemp seed protein on blood pressure in normotensive animals (101136). Furthermore, hempseed oil consumption does not seem to reduce blood pressure in humans (101144).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hemp might interfere with hormone therapy due to its estrogenic effects.  Details In an ovariectomized animal model, a diet containing hemp seed 1%, 2%, or 10% resulted in normalized plasma levels of 17-beta-estradiol (101132). The mechanism of action for this effect is unclear.

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ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, malic acid might increase the risk of hypotension when taken with antihypertensive drugs.  Details Animal research shows that malic acid isolated from tagetes roots can reduce mean arterial blood pressure (26970).

(Read more about MALIC ACID)

AMIODARONE (Cordarone) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, papaya extract may increase the levels and clinical effects of amiodarone.  Details Animal research in rats shows that a single oral dose of papaya extract, as well as multiple doses of papaya extract daily over 14 days, prior to a single dose of amiodarone delays the time to maximum amiodarone concentration. However, only the 14-day papaya extract regimen increases systemic amiodarone exposure by 60% to 70% (93093). This interaction has not been reported in humans.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Concomitant use of antidiabetic drugs with fermented papaya can produce additive effects. It is unclear if other forms of papaya have the same effect.  Details A small low-quality clinical study in patients with type 2 diabetes who are taking glibenclamide shows that taking a fermented papaya preparation 3 grams daily for 2 months decreases fasting and postprandial blood glucose levels when compared to baseline. Additionally, of the 25 patients in the study, 9 required a reduction in glibenclamide dose (67902).

LEVOTHYROXINE (Synthroid, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, consuming large quantities of papaya fruit can reduce the clinical effects of levothyroxine.  Details In one case-report, a 37-year-old male with a history of thyroidectomy who was stabilized on levothyroxine for 5 years presented with hypothyroidism after consuming 5-6 papaya fruits daily for 14 days during vacation. In a controlled re-challenge test involving 5-6 papayas daily, the patient remained euthyroid for 7 days, but developed mild hypothyroidism after 14 days. Both times, thyroid levels normalized 40-45 days after discontinuing papaya (93087).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of warfarin with papain-containing papaya extract might increase the effects and side effects of warfarin.  Details In one case report, a patient previously stable on warfarin was found to have an international normalization ratio (INR) of 7.4, which was attributed to ingestion of a supplement containing papain from papaya extract (613).

(Read more about PAPAYA)

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, senna might increase the risk of adverse effects when taken with digoxin.  Details Overuse/abuse of senna increases the risk of adverse effects from cardiac glycosides, such as digoxin, due to potassium depletion (15425).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, senna might increase the risk of hypokalemia when taken with diuretic drugs.  Details Overuse of senna might compound diuretic-induced potassium loss and increase the risk for hypokalemia (15425).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking senna may interfere with the absorption of exogenous estrogens.  Details Some preliminary clinical evidence suggests that senna reduces the absorption of estradiol and decreases serum concentrations of estrone and estrone sulfate by decreasing intestinal transit time (74647,74651).

STIMULANT LAXATIVES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, senna might increase the risk for fluid and electrolyte loss when taken with other stimulant laxatives.  Details Senna is a stimulant laxative; concomitant use with other stimulant laxatives might compound fluid and electrolyte loss (19,15425).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, excessive use of senna might increase the effects of warfarin.  Details Senna has stimulant laxative effects and can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. In one case report, excessive use of senna for 3 weeks resulted in diarrhea, bloody stools, and an elevated INR of 11.9 (16530).

(Read more about SENNA)

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = A Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.  Details High intake of dietary sodium can increase systolic and diastolic blood pressure (26222). Also, high intake of sodium may necessitate increased use of antihypertensive medications to achieve blood pressure control in some patients, such as those with chronic kidney disease (26223).

CORTICOSTEROIDS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.  Details Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone (4425).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Altering dietary intake of sodium might alter the levels and clinical effects of lithium.  Details High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion (26225). Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate (26224,26225). Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L (112909). Patients taking lithium should avoid significant alterations in their dietary intake of sodium.

SODIUM-CONTAINING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.  Details The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population (100310). Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.

TOLVAPTAN (Samsca) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.  Details Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia (29406). Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.

(Read more about SODIUM)

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, stevia might increase the risk for hypoglycemia when combined with antidiabetes drugs.  Details Preliminary clinical research in patients with type 2 diabetes suggests that taking a single dose of stevia extract 1000 mg reduces postprandial blood glucose levels when taken with a meal (11812). However, other clinical research in patients with type 1 or type 2 diabetes suggests that taking stevioside 250 mg three times daily does not significantly affect blood glucose levels or glycated hemoglobin (HbA1C) after three months of treatment (16705).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining stevia or stevia constituents with antihypertensive agents might increase the risk of hypotension.  Details Stevia extract and stevioside might lower blood pressure in patients with hypertension (3745,3747,5031,11809,11810). However, other clinical research suggests that stevioside does not significantly lower blood pressure in patients with hypertension (16706).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, stevia might decrease clearance and increase levels of lithium.  Details Animal research suggests that stevia extracts might have diuretic activity (3746,3747). Theoretically, increased reabsorption of lithium along with sodium might reduce excretion and increase levels of lithium.

(Read more about STEVIA)

General ...Orally, beet seems to be well tolerated when used for medicinal purposes, short term.
Most Common Adverse Effects:
Orally: Red stools and red urine.
Serious Adverse Effects (Rare):
Orally: Hypocalcemia and kidney damage when ingested in large amounts.

Endocrine ...Theoretically, ingestion of large quantities of beets could lead to hypocalcemia because of the oxaluric acid content (18).

Gastrointestinal ...Orally, beet juice may cause red stools (94470,97726,100142,100145,105762). This red coloring of the stools is not harmful. Additionally, beet supplementation has been reported to cause black stools. In one case, a 79-year-old male on apixaban and clopidogrel presented with black stools, nausea, and vomiting after taking beet pills 2-3 days prior. The likelihood of upper gastrointestinal bleed was determined to be low based on factors such as normal vital signs and lack of severe anemia. The patient was diagnosed with beet-induced pseudo-hematochezia which was successfully treated with fluids and discontinuation of the beet supplement (113426).
Other less common gastrointestinal side effects include loose stools, constipation, and nausea (100149).

Genitourinary ...Orally, beet is known to produce red or pink urine (beeturia) in some people (32569,34134,94464,94470,97725,97726,100142,100145,100152,105762,113422). However, this red coloring of the urine is not harmful and dissipates after about 12 hours (113422).

Neurologic/CNS ...Orally, vivid dreams and worsening headaches have each occurred in one person in a clinical trial, although it is not clear if this is due to beet (97723).

Renal ...Theoretically, ingestion of large quantities of beets could lead to kidney damage due to its oxaluric acid content (18).

(Read more about BEET)

General ...Orally and topically, German chamomile is well tolerated.
Most Common Adverse Effects:
Orally and topically: Allergic reactions and irritation.

Dermatologic ...Topically, German chamomile may cause allergic dermatitis and eczema (9766,9768,10377,110318).

Gastrointestinal ...When used topically as an oral rinse, German chamomile has been reported to cause nausea and burning in the mouth in some patients (99853).

Immunologic ...Orally, German chamomile tea can cause allergic reactions including severe hypersensitivity reactions and anaphylaxis in some patients (567). In one case report, a 47-year-old female who tolerated drinking chamomile tea, reported sneezing, nasal and ocular itching, red and watery eyes, and severe rhinorrhea after 10 years of occupational exposure to German chamomile dust (90542).

Ocular/Otic ...If used near the eyes, German chamomile can cause irritation (10377).

(Read more about GERMAN CHAMOMILE)

General ...Orally, hemp products are generally well tolerated in food amounts. In larger amounts, hemp seed oil seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Rare cases of anaphylaxis have been reported. Long QT syndrome, torsades de pointes, and syncope have also been reported rarely.

Cardiovascular ...Acquired long QT syndrome, torsades de pointes, and syncope have been reported in a 56-year-old woman following the intake of supplements containing hemp oil. The hemp supplements provided cannabidiol (CBD), and possibly cannabigerol (CBG). Although the exact dose is unknown, up to six times the recommended dose had been used for approximately 6 weeks, in combination with a supplement containing berberine. While hospitalized, intravenous magnesium and saline were used to stabilize heart rhythm. It is unknown whether this adverse effect was related to the hemp oil, berberine, or their interaction (110104).

Hepatic ...Orally, there is a case report of elevated liver enzymes and hepatitis in a two-year-old boy given hemp extract 2. 5 mL, providing 125 mg phytocannabinoid, five to eight times daily for infantile spasms and refractory seizures. The total dose of phytocannabinoids was approximately 60-100 mg/kg daily (110287).

Immunologic ...Orally, there are case reports of allergy to hemp seed, although this is uncommon (101140,101154). A 44-year-old male developed hives during a meal of hemp seed-crusted seafoods. Later, he developed facial swelling, shortness of breath, and problems speaking. Evaluation revealed allergy to a specific protein in hemp seed. He did not react to smoked cannabis (101140). In other cases, anaphylaxis, facial swelling, and worsening asthma have been reported in association with a first exposure to hemp seed, although some had smoked cannabis previously (101154).
Topically, a case of patch-test confirmed allergic contact dermatitis to hemp seed oil has been reported in a 22-year-old woman. The initial rash started at the application point on her back and spread to her arms, hands, and neck (110288).
Airborne exposure to hemp pollen is a relatively common cause of allergic respiratory symptoms in some locations (101155).

Neurologic/CNS ...Orally, cases of acute cannabinoid toxicity with neurological symptoms in children and adults have been associated with intake of hemp seed oil. There is a case report of decreased alertness, stupor, bloodshot eyes, and fixed gaze in a 2-year-old male probably related to the intake of one teaspoon hemp seed oil (CANAH) containing 0.06% delta-9-tetrahydrocannabinol (THC) twice daily for 3 weeks. After stopping the oil, irritability was reported over the next few days (101153).

(Read more about HEMP)

General ...Orally, malic acid seems to be well tolerated. Topically, malic acid seems to be well tolerated when applied to oral mucosal surfaces. A thorough evaluation of safety outcomes with topical malic acid use on the skin has not been conducted.
Most Common Adverse Effects:
Topical: Eye irritation, skin irritation, and skin peeling.

Dermatologic ...Topically, malic acid may cause moderate to strong skin irritation and peeling (26968,95564,95595). In patients first patch tested with malic acid, next instructed to avoid foods containing malic or citric acid, and then challenged with foods containing high amounts of malic and citric acid, skin reactions including immediate hives and delayed contact dermatitis occurred (26968).

Gastrointestinal ...Orally, diarrhea and nausea have been reported for patients taking a specific combination product (Super Malic) containing malic acid1200 mg and magnesium 300 mg twice daily. However, it is unclear if the adverse effect is due to malic acid, since it is known that magnesium can have a laxative effect at this dose (3262).

Ocular/Otic ...Topically, malic acid might irritate the eyes, especially in formulations containing 2. 27% or more malic acid (26968,95564,95595).

(Read more about MALIC ACID)

General ...Orally, papaya fruit is well tolerated when consumed in food amounts. Papaya leaf extract seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Nausea and vomiting from papaya leaf extract.
Topically: Burning sensation from unripe papaya.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions.

Dermatologic ...Orally, high doses of papaya might cause yellow skin discoloration. A case of carotenemia has been reported for a 42-year-old female who consumed 1.5-2 papayas daily for 6 months. The condition resolved when she stopped eating papayas (67929).
Topically, unripe papaya fruit may cause occasional burning sensation when applied to skin ulcers (67856).

Gastrointestinal ...Orally, the leaf extract has been reported to cause nausea and vomiting in clinical research (102799). A case of esophageal perforation has been reported for a previously healthy 27-year-old female who used papain, a constituent of papaya latex, to digest a piece of meat stuck in her esophagus (93083).

Immunologic ...Orally, papain, a constituent of raw, unripe papaya, has been reported to cause allergic reactions in sensitive individuals, including itchy watery eyes, runny nose, sneezing, abdominal cramps, sweating, and diarrhea (6,967). Papaya may also cause hypersensitivity reactions such as systemic contact dermatitis, which occur more commonly in people who are allergic to latex (6197,7853,57635). A case of systemic contact dermatitis has been reported for a 55-year-old female with no prior history of atopic disease or drug allergy after ingesting a throat lozenge containing papaya juice (67942).

Other ...In regions with arsenic-contaminated soil, papaya fruits contain a higher mean concentration of arsenic compared with many other forms of vegetation grown in the regions. Eating papaya from these regions is thought to contribute to higher dietary levels of arsenic (32461,67879).

(Read more about PAPAYA)

General ...Orally, senna is generally well-tolerated when used short-term in appropriate doses.
Most Common Adverse Effects:
Orally: Abdominal pain and discomfort, cramps, diarrhea, flatulence, nausea, fecal urgency, and urine discoloration.
Serious Adverse Effects (Rare):
Orally: Skin eruptions.

Cardiovascular ...Excessive use can cause potassium depletion and other electrolyte abnormalities (15425). In theory, this could cause potentially dangerous changes in heart rhythm. A small decrease in heart rate was seen in one clinical study (74587).

Dermatologic ...In adults, there are rare case reports of skin eruptions associated with senna, including erythema multiforme, fixed drug eruption, lichenoid reaction, toxic epidermal necrolysis, urticaria, photosensitivity, and contact dermatitis (96558). Infants and young children given senna products have experienced contact reactions on the buttocks due to prolonged exposure to stool while wearing a diaper overnight. These reactions range from erythema with small blisters, to large fluid-filled blisters with skin sloughing, as occurs with second degree burns (96559). In a case series of children treated with senna for chronic constipation, burn-like reactions occurred in 2.2%, typically with higher doses (mean 60 mg/day, range 35.2 to 150 mg/day) (96558,96559). These reactions can be avoided by giving senna early in the day, so that bowel movements occur at a time when diapers can be changed quickly (96559).

Gastrointestinal ...Orally, senna can cause abdominal pain and discomfort, cramps, bloating, flatulence, nausea, fecal urgency, and diarrhea (15427,15434,15435,15436,15439,15440,15441,105955). Chronic use has also been associated with "cathartic colon," radiographically diagnosed anatomical changes to the colon such as benign narrowing, colonic dilation, and loss of colonic folds (15428). The clinical relevance of these findings is unclear. Chronic use can also cause pseudomelanosis coli (pigment spots in intestinal mucosa) which is harmless, usually reverses with discontinuation, and is not associated with an increased risk of developing colorectal adenoma or carcinoma (6138). The cathartic properties of senna leaf are greater than the fruit (15430). Thus, the American Herbal Products Association only warns against long-term use of senna leaf (12).

Hepatic ...Chronic liver damage, portal vein thrombosis, and hepatitis have been reported following oral use of senna alkaloids, such as in tea made from senna leaves (13057,13095,41431,74560,74564,74584,105956). There is a case report of hepatitis in a female who consumed moderate amounts of senna tea. The patient was a poor metabolizer of cytochrome P450 2D6 (CYP2D6). It's thought that moderate doses of senna in this patient led to toxic hepatitis due to the patient's reduced ability to metabolize and eliminate the rhein anthrone metabolites of senna, which are thought to cause systemic toxicity (13057). There is also a case of liver failure, encephalopathy, and renal insufficiency in a female who consumed 1 liter/day of senna tea, prepared from 70 grams of dried senna fruit, over 3 years (13095). In another case report, a 3-year-old female presented with hepatitis that led to pancytopenia after drinking tea made from 2-3 grams dry senna leaves three times or more weekly for over one year (105956).

Immunologic ...In one case report, a 19-year-old male developed anaphylaxis with dyspnea, facial edema, and hives. This reaction was determined to be caused by the senna content in a specific combination product (Delgaxan Plus, Pompadour Ibérica) that the patient ingested (105957).

Musculoskeletal ...Hypertrophic osteoarthropathy, finger clubbing, cachexia, and tetany have been reported from excessive oral senna use in humans (15426,74580,74582,74620,74625).

Renal ...Nephrocalcinosis has been reported as a result of oral senna overuse (74582).

(Read more about SENNA)

General ...Orally, sodium is well tolerated when used in moderation at intakes up to the Chronic Disease Risk Reduction (CDRR) intake level. Topically, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Worsened cardiovascular disease, hypertension, kidney disease.

Cardiovascular ...Orally, intake of sodium above the CDRR intake level can exacerbate hypertension and hypertension-related cardiovascular disease (CVD) (26229,98176,100310,106263). A meta-analysis of observational research has found a linear association between increased sodium intake and increased hypertension risk (109398). Observational research has also found an association between increased sodium salt intake and increased risk of CVD, mortality, and cardiovascular mortality (98177,98178,98181,98183,98184,109395,109396,109399). However, the existing research is unable to confirm a causal relationship between sodium intake and increased cardiovascular morbidity and mortality; high-quality, prospective research is needed to clarify this relationship (100312). As there is no known benefit with increased salt intake that would outweigh the potential increased risk of CVD, advise patients to limit salt intake to no more than the CDRR intake level (100310).
A reduction in sodium intake can lower systolic blood pressure by a small amount in most individuals, and diastolic blood pressure in patients with hypertension (100310,100311,106261). However, post hoc analysis of a small crossover clinical study in White patients suggests that 24-hour blood pressure variability is not affected by high-salt intake compared with low-salt intake (112910). Additionally, the available research is insufficient to confirm that a further reduction in sodium intake below the CDRR intake level will lower the risk for chronic disease (100310,100311). A meta-analysis of clinical research shows that reducing sodium intake increases levels of total cholesterol and triglycerides, but not low-density lipoprotein (LDL) cholesterol, by a small amount (106261).
It is unclear whether there are safety concerns when sodium is consumed in amounts lower than the adequate intake (AI) levels. Some observational research has found that the lowest levels of sodium intake might be associated with increased risk of death and cardiovascular events (98181,98183). However, this finding has been criticized because some of the studies used inaccurate measures of sodium intake, such as the Kawasaki formula (98177,98178,101259). Some observational research has found that sodium intake based on a single 24-hour urinary measurement is inversely correlated with all-cause mortality (106260). The National Academies Consensus Study Report states that there is insufficient evidence from observational studies to conclude that there are harmful effects from low sodium intake (100310).

Endocrine ...Orally, a meta-analysis of observational research has found that higher sodium intake is associated with an average increase in body mass index (BMI) of 1. 24 kg/m2 and an approximate 5 cm increase in waist circumference (98182). It has been hypothesized that the increase in BMI is related to an increased thirst, resulting in an increased intake of sugary beverages and/or consumption of foods that are high in salt and also high in fat and energy (98182). One large observational study has found that the highest sodium intake is not associated with overweight or obesity when compared to the lowest intake in adolescents aged 12-19 years when intake of energy and sugar-sweetened beverages are considered (106265). However, in children aged 6-11 years, usual sodium intake is positively associated with increased weight and central obesity independently of the intake of energy and/or sugar-sweetened beverages (106265).

Gastrointestinal ...In one case report, severe gastritis and a deep antral ulcer occurred in a patient who consumed 16 grams of sodium chloride in one sitting (25759). Chronic use of high to moderately high amounts of sodium chloride has been associated with an increased risk of gastric cancer (29405).

Musculoskeletal ...Observational research has found that low sodium levels can increase the risk for osteoporosis. One study has found that low plasma sodium levels are associated with an increased risk for osteoporosis. Low levels, which are typically caused by certain disease states or chronic medications, are associated with a more than 2-fold increased odds for osteoporosis and bone fractures (101260).
Conversely, in healthy males on forced bed rest, a high intake of sodium chloride (7.7 mEq/kg daily) seems to exacerbate disuse-induced bone and muscle loss (25760,25761).

Oncologic ...Population research has found that high or moderately high intake of sodium chloride is associated with an increased risk of gastric cancer when compared with low sodium chloride intake (29405). Other population research in patients with gastric cancer has found that a high intake of sodium is associated with an approximate 65% increased risk of gastric cancer mortality when compared with a low intake. When zinc intake is taken into consideration, the increased risk of mortality only occurred in those with low zinc intake, but the risk was increased to approximately 2-fold in this sub-population (109400).

Pulmonary/Respiratory ...In patients with hypertension, population research has found that sodium excretion is modestly and positively associated with having moderate or severe obstructive sleep apnea. This association was not found in normotensive patients (106262).

Renal ...Increased sodium intake has been associated with impaired kidney function in healthy adults. This effect seems to be independent of blood pressure. Observational research has found that a high salt intake over approximately 5 years is associated with a 29% increased risk of developing impaired kidney function when compared with a lower salt intake. In this study, high salt intake was about 2-fold higher than low salt intake (101261).

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General ...Orally, stevia and steviol glycosides appear to be well tolerated. Most minor adverse effects seem to resolve after the first week of use.
Most Common Adverse Effects:
Abdominal bloating, dizziness, headache, myalgia, nausea, and numbness.
Serious Adverse Effects (Rare):
Allergic reactions.

Gastrointestinal ...Orally, stevia and steviol glycosides such as stevioside, can cause gastrointestinal adverse effects such as abdominal fullness and nausea. However, these generally resolve after the first week of use (11809,11810).

Immunologic ...Theoretically, stevia might cause allergic reactions in individuals sensitive to plants in the Asteraceae/Compositae family (11811). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Musculoskeletal ...Orally, stevia and steviol glycosides may cause myalgia, but this generally resolves after the first week of use (11809,11810).

Neurologic/CNS ...Orally, stevia and steviol glycosides may cause headache, dizziness, and numbness (11809,11810).

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