Skin Balance [Discontinued] by Health Concerns

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. Although there has been interest in using oral bupleurum for asthma, there is insufficient reliable information about the clinical effects of bupleurum for this purpose.
• Autoimmune thyroiditis. Oral bupleurum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with Hashimoto's thyroiditis receiving conventional levothyroxine supplementation shows that taking bupleurum 10 grams in combination with other traditional Chinese medicines for 8 weeks improves thyroid antibody levels, thyroid stimulating hormone levels, depression scores, and anxiety scores when compared with control at 24 weeks follow up. However, TSH levels were normalized by week 8 in both groups, and bupleurum does not improve free T3 or T4 levels (112353). It is unclear if these effects are due to bupleurum, other ingredients, or the combination.
• Cancer. Although there has been interest in using oral bupleurum for cancer, there is insufficient reliable information about the clinical effects of bupleurum for this purpose.
• Depression. Oral bupleurum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 55 Chinese studies shows that taking herbal combinations which include Bupleurum chinense root for 2-12 weeks slightly reduces depression severity on the Hamilton Rating Scale for Depression (HRSD) when compared with fixed standard doses of selective serotonin reuptake inhibitors (SSRIs). Using bupleurum mixtures in combination with SSRIs greatly reduces depression severity on the HRSD when compared with SSRIs alone (104103). However, the validity of this analysis is limited by considerable heterogeneity amongst the studies, which were generally of low quality and at a high risk of bias. There were 49 different bupleurum-containing formulas used in the included studies, and these contained 103 different herbs. It is unclear whether any effects were due to bupleurum, other herbs, or the combinations. It is also unclear what the depression severity was at baseline, whether SSRIs were given in sufficient doses and durations, and whether patients were treatment-naïve.
• Dysmenorrhea. Although there has been interest in using oral bupleurum for dysmenorrhea, there is insufficient reliable information about the clinical effects of bupleurum for this purpose.
• Epilepsy. Although there has been interest in using oral bupleurum for epilepsy, there is insufficient reliable information about the clinical effects of bupleurum for this purpose.
• Hepatitis B. Oral bupleurum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with chronic hepatitis B shows that taking a specific combination product (sho-saiko-to) 5.4 grams daily for 24 weeks decreases liver enzyme levels when compared with taking this same combination product at a dose of 0.5 grams daily (37391). Another small clinical study in children with chronic hepatitis B shows that taking this same combination product at an unknown dose increases the production of hepatitis B antibodies and increases the clearance of hepatitis B virus when compared with historical controls (37384). However, the clinical significance of these changes is unknown.
• Influenza. Oral bupleurum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with H1N1 influenza shows that taking a specific bupleurum-containing combination decoction (chima qingwen) twice daily for 5 days is as effective as taking oseltamivir 75 mg twice daily for 5 days for improving symptoms by at least 30% (100167).
• Liver cancer. Oral bupleurum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with hepatitis B and liver cirrhosis shows that taking a specific bupleurum-containing combination product (sho-saiko-to, TJ-9, Tsumura and Co.) 7.5 grams daily for 60 months along with conventional medicine reduces the risk of developing liver cancer when compared with conventional treatment alone in patients without anti-hepatitis B antibodies. Taking this combination product did not reduce the risk of developing liver cancer in patients with anti-hepatitis B antibodies (37410).
• Pain. Although there has been interest in using oral bupleurum for pain, there is insufficient reliable information about the clinical effects of bupleurum for this purpose.
• Peptic ulcers. Although there has been interest in using oral bupleurum for peptic ulcers, there is insufficient reliable information about the clinical effects of bupleurum for this purpose.
• Respiratory tract infections. Although there has been interest in using oral bupleurum for various respiratory tract infections, including bronchitis and the common cold, there is insufficient reliable information about the clinical effects of bupleurum for these conditions. More evidence is needed to rate bupleurum for these uses.

(Read more about BUPLEURUM)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). Although there is interest in using oral dong quai for atopic dermatitis, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Chronic kidney disease (CKD). There is limited evidence on the use of dong quai in patients with CKD. Details: A large propensity score-matched observational study over 15 years in Taiwanese adults with CKD suggests that taking dong quai is associated with a 5.1% risk of end-stage renal disease (ESRD) and 38% risk of overall mortality when compared with 7% and 56%, respectively, in controls. Higher cumulative doses (i.e., 15 grams or more) and longer duration of exposure (i.e., > 60 days) are also associated with fewer ESRD events (112362). However, the interpretation of these findings is limited by the lack of exact dosage information and retrospective study design.
• Coronary heart disease (CHD). Intravenous dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with CHD shows that injecting 20 mL of an intravenous solution containing dong quai, ginseng, and astragalus (Yi-qi Huo-xue Injection) daily for 2 weeks reduces the frequency and severity of angina episodes when compared with placebo. It also seems to increase exercise tolerance and improve left ventricular function when compared with placebo (33046). It is unclear if these benefits are due to dong quai, other ingredients, or the combination.
• Dysmenorrhea. Although there is interest in using oral dong quai for dysmenorrhea, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Hypertension. Although there is interest in using oral dong quai for hypertension, there is insufficient reliable information about the clinical effects of dong quai for this purpose.
• Idiopathic interstitial pneumonia. Oral dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 17 studies conducted in China in patients with idiopathic interstitial pneumonia concludes that adding traditional Chinese medicine combinations containing dong quai root and astragalus root to treatment with conventional medicines improves pulmonary function index, six-minute walking distance, and the Borg scale of perceived exertion when compared with conventional treatment alone (103618). The included studies are of low quality, include a range of treatment durations from 1-12 months, and vary in the conventional medicines and Chinese herb combinations used. The doses of dong quai used were not stated.
• Infertility. Although there is interest in using oral dong quai for infertility, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Iron deficiency anemia. Although there is interest in using oral dong quai for iron deficiency anemia, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Menopausal symptoms. There is inconsistent and contradictory evidence about the effect of dong quai on menopausal symptoms. Benefits have only been seen when it is used in combination with other ingredients; its effect when used alone is unclear. Details: Some clinical research shows that taking dong quai, 1.5 grams three times daily for 24 weeks, does not affect menopausal symptoms (738). Other clinical research shows that dong quai improves menopausal symptoms when used in combination with other constituents. In one clinical trial, taking five chewable tablets of a specific combination of dong quai and chamomile (Climex) daily for 12 weeks reduced the frequency and severity of hot flushes when compared with placebo (48445). In another trial, taking a combination providing dong quai 75 mg, along with American ginseng, black cohosh, milk thistle, red clover, and vitex agnus-castus (Phyto-Female Complex) twice daily for 3 months reduces menopausal symptoms, including the number and intensity of hot flushes, the number of night sweats, and sleep quality (19552). Taking another combination product containing dong quai, burdock root, licorice root, motherwort, and Mexican wild yam root, 500 mg three times daily for 3 months, also reduces menopausal symptoms when compared with placebo (48522). It is unclear if the beneficial effects in these studies were due to dong quai, other ingredients, or a combination of ingredients.
• Migraine headache. Oral dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with menstrual migraine shows that taking a combination of soy isoflavones 60 mg, dong quai 100 mg, and black cohosh 50 mg daily for 24 weeks reduces the frequency of attacks when compared with placebo (35797). It is unclear if this effect is due to dong quai, other ingredients, or the combination.
• Osteoporosis. Although there is interest in using oral dong quai for osteoporosis, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Peptic ulcers. Although there is interest in using oral dong quai for peptic ulcers, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Premature ejaculation. Topical dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In one preliminary clinical trial in patients with premature ejaculation, a multi-ingredient cream preparation (SS Cream) containing dong quai, Panax ginseng root, Cistanches deserticola, Zanthoxyl species, Torlidis seed, clove flower, Asiasari root, cinnamon bark, and toad venom was applied to the glans penis 1 hour prior to intercourse and washed off immediately before intercourse. Patients using the cream had significantly improved ejaculatory latency when compared with placebo cream (2537). It is unclear if this effect is due to dong quai, other ingredients, or the combination.
• Premenstrual syndrome (PMS). Although there is interest in using oral dong quai for PMS, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Psoriasis. Although there is interest in using oral dong quai for psoriasis, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Pulmonary hypertension. Preliminary clinical research shows that intravenous dong quai may be effective in patients with pulmonary hypertension. Details: Some preliminary clinical research in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension shows that intravenous administration of 250 mL of a solution containing dong quai 25%, once daily for 5-10 days, reduces pulmonary arterial pressure and pulmonary vascular resistance when compared to baseline (48438,48442,48443). The validity of these findings is limited by the lack of comparator groups.
• Rheumatoid arthritis (RA). Although there is interest in using oral dong quai for RA, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Stroke. Preliminary evidence does not support the use of intravenous dong quai for acute ischemic stroke. Details: Preliminary clinical research in patients with acute ischemic stroke shows that administering 200 mL of a solution containing dong quai 25% intravenously daily for 20 days does not improve neurological symptoms when compared with dextran-40 (48483). More evidence is needed to rate dong quai for these uses.

(Read more about DONG QUAI)

POSSIBLY EFFECTIVE

• Sinusitis. Clinical research shows that taking gentian orally in a specific combination product (SinuComp; Sinupret) that also contains elderflower, verbena, cowslip flower, and sorrel improves the symptoms of acute or chronic sinusitis (374,379). In one cohort study, taking this specific combination product orally three times daily with mometasone furoate nasal spray 200 mcg twice daily for 7 days reduces symptoms related to acute sinusitis when compared with using mometasone nasal spray alone (95907).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Weight loss. Preliminary clinical research in healthy adults shows that consuming a pudding containing microencapsulated gentian root extract 1.25 g at breakfast modestly reduces caloric intake over 24 hours, but does not affect self-reported feelings of hunger or fullness, when compared with placebo pudding (96534). More evidence is needed to rate gentian for this use.

(Read more about GENTIAN)

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

(Read more about GOLDTHREAD)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). Preliminary clinical research shows that applying an ointment containing 5% each of the extracts of heart's ease, gotu kola, and Oregon grape twice daily for 4 weeks does not improve eczema when compared with a base cream. However, patients with eczema on skin exposed to cold weather might experience some improvement (67372).
• Chronic obstructive pulmonary disease (COPD). Preliminary clinical research in men aged 40-70 years with a history of smoking and stage 2 COPD shows that taking a combination of heart's ease 165 mg, calendula flowers 165 mg, and elderberry 165 mg (Inflaminat, INAT-Farma), 3 capsules daily for 6 months, modestly improves the score on the 5-point breathlessness, cough, and sputum scale (BCSS) and the mean forced expiratory volume in 1 second (FEV1), compared with no changes in the placebo group. However, the number of COPD exacerbations per month does not seem to be affected (103629). It is unclear if these effects are due to heart's ease, other ingredients, or the combination. More evidence is needed to rate heart's ease for these uses.

(Read more about HEART'S EASE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral honeysuckle extract is beneficial in patients with age-related cognitive decline. Details: A small clinical study in elderly adults shows that taking honeysuckle (Lonicera caerulea) berry extract 200-400 mg, 90 minutes prior to a cognitive test, improves episodic memory, but not working memory or executive function tasks, when compared with placebo (103876). The long-term effects of honeysuckle on cognitive decline are unclear.
• Atopic dermatitis (eczema). Although there has been interest in using topical honeysuckle for atopic dermatitis, there is insufficient reliable information about the clinical effects of honeysuckle for this purpose.
• Bronchiolitis. Intravenous honeysuckle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with respiratory syncytial virus (RSV) infection shows that intravenous administration of a combination of honeysuckle, Baikal skullcap, and forsythia might decrease the duration of symptoms of bronchiolitis when compared with a control group (12613). It is unclear if these findings are due to honeysuckle, other ingredients, or the combination.
• Diabetes. Although there has been interest in using oral honeysuckle for diabetes, there is insufficient reliable information about the clinical effects of honeysuckle for this purpose.
• Dyspepsia. It is unclear if oral honeysuckle flower bud extract is beneficial in patients with dyspepsia. Details: A small clinical study in patients with functional dyspepsia shows that taking honeysuckle (Lonicera japonica) flower bud extract 125 mg twice daily for 8 weeks improves gastrointestinal symptom scores when compared with placebo (103877).
• Postoperative infection. Topical honeysuckle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large open-label trial in adults with obstructive sleep apnea recovering from uvulopalatopharyngoplasty shows that gargling with honeysuckle in combination with numerous other herbs 25 mL for 5 minutes 4 times daily for 2 weeks does not reduce post-operative wound infection when compared with saline placebo (112867). The interpretation of this study is limited by the unclear dose of honeysuckle.
• Postoperative pain. Topical honeysuckle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large open-label trial in adults with obstructive sleep apnea recovering from uvulopalatopharyngoplasty shows that gargling with honeysuckle in combination with numerous other herbs 25 mL for 5 minutes 4 times daily for 2 weeks improves post-operative resting, swallowing throat pain, and patient comfort when compared with saline placebo (112867). It is unclear if this effect is due to honeysuckle, other ingredients, or the combination. The interpretation of this study is also limited by the unclear dose of honeysuckle.
• Pruritus. Although there has been interest in using topical honeysuckle for pruritus, there is insufficient reliable information about the clinical effects of honeysuckle for this purpose.
• Respiratory tract infections. Although there has been interest in using oral honeysuckle for various respiratory tract infections, including bronchitis, the common cold, influenza, and pneumonia, there is insufficient reliable information about the clinical effects of honeysuckle for these conditions.
• Rheumatoid arthritis (RA). Although there has been interest in using oral honeysuckle for RA, there is insufficient reliable information about the clinical effects of honeysuckle for this purpose.
• Urinary tract infections (UTIs). Although there has been interest in using oral honeysuckle for UTIs, there is insufficient reliable information about the clinical effects of honeysuckle for this purpose.
• Wound healing. Although there has been interest in using topical honeysuckle for wound healing, there is insufficient reliable information about the clinical effects of honeysuckle for this purpose. More evidence is needed to rate honeysuckle for these uses.

(Read more about HONEYSUCKLE)

POSSIBLY EFFECTIVE

• Chronic kidney disease (CKD). Oral rehmannia acteosides might reduce proteinuria when used in conjunction with angiotensin II receptor blockers in patients with CKD. Details: A large clinical trial in adults with chronic glomerulonephritis shows that taking rehmannia acteosides extract 400 mg twice daily, in conjunction with irbesartan 150 mg daily, for 8 weeks decreases proteinuria by 36%, compared with a reduction of 28% with irbesartan alone (93662).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aplastic anemia. It is unclear if oral rehmannia is beneficial in patients with aplastic anemia. Details: A small clinical study in adults with aplastic anemia shows that taking rehmannia polysaccharide (dose unknown), in conjunction with stanozolol, increases the incidence of symptom remission by 45% when compared with stanozolol alone (70704).
• Atopic disease. Although there has been interest in using oral rehmannia for atopic disease, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Diabetes. Although there has been interest in using oral rehmannia for diabetes, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Diabetic nephropathy. Oral rehmannia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in adults with chronic kidney disease due to type 2 diabetes receiving standard care with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker shows that taking a specific combination product (Rehmannia-6, PuraPharm) containing rehmannia, Japanese cornel dogwood, wild yam, poria mushroom, Asian water plantain, and peony root bark twice daily for 48 weeks modestly slows the decline in kidney function when compared with standard care alone (112821). It is unclear if this effect is due to rehmannia, other ingredients, or the combination.
• Metabolic syndrome. Although there has been interest in using oral rehmannia for metabolic syndrome, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Obesity. It is unclear if oral rehmannia root extract is beneficial in patients with obesity. Details: A very small clinical study in females with obesity shows that taking steamed rehmannia root extract 4 grams twice daily for 8 weeks decreases waist circumference by 2.6%, but does not affect body weight or body fat percentage, when compared to baseline (93660). The validity of these findings is limited by the lack of a control group.
• Osteoporosis. Although there has been interest in using oral rehmannia for osteoporosis, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral rehmannia for RA, there is insufficient reliable information about the clinical effects of rehmannia for this purpose. More evidence is needed to rate rehmannia for these uses.

(Read more about REHMANNIA)

POSSIBLY EFFECTIVE

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

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about RHUBARB)

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)

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Bupleurum has been used with apparent safety as part of a multi-ingredient decoction (sho-saiko-to) for up to 5 years (37391,37410). It has also been used with apparent safety as part of another multi-ingredient decoction (chima qingwen) at doses of up to 40 grams bupleurum daily for up to 5 days (100167).

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

(Read more about BUPLEURUM)

POSSIBLY SAFE ...when used orally and appropriately. Dong quai has been used with apparent safety in a dose of 4.5 grams daily for 24 weeks, or in combination with other ingredients in doses of up to 150 mg daily for up to 6 months (19552,35797). ...when used intravenously as a 25% solution, in a dose of 200-250 mL daily for up to 20 days (48438,48442,48443,48483).

POSSIBLY UNSAFE ...when used orally in large amounts, long-term. Theoretically, long-term use of large amounts of dong quai could be harmful. Dong quai contains several constituents such as bergapten, safrole, and isosafrole that are considered carcinogenic (7162). There is insufficient reliable information available about the safety of dong quai when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used orally. Dong quai has uterine stimulant and relaxant effects (8142); theoretically, it could adversely affect pregnancy. Observational research has found that intake of An-Tai-Yin, an herbal combination product containing dong quai and parsley, during the first trimester is associated with an increased risk of congenital malformations of the musculoskeletal system, connective tissue, and eyes (15129).

LACTATION:
Insufficient reliable information available; avoid use.

(Read more about DONG QUAI)

LIKELY SAFE ...when the root preparations are used in amounts commonly found in foods. Gentian root is categorized by the FDA as a safe food additive flavoring in the US (4912).

POSSIBLY SAFE ...when gentian root is used orally in a specific combination that contains gentian root, elderflower, verbena, cowslip flower, and sorrel (SinuComp, Sinupret) (374,379,95907). There is insufficient reliable information available about the safety of the topical use of gentian.

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of gentian in medicinal amounts during pregnancy and lactation; avoid using.

(Read more about GENTIAN)

There is insufficient reliable information available about the safety of goldthread when used in adults in medicinal amounts.

CHILDREN: LIKELY UNSAFE
when used orally in newborns. The berberine constituent of goldthread can cause kernicterus in newborns, particularly preterm neonates with hyperbilirubinemia (2589).

PREGNANCY: LIKELY UNSAFE
when used orally. Berberine is thought to cross the placenta and may cause harm to the fetus. Kernicterus has developed in newborn infants exposed to berberine (2589). Preliminary evidence suggests that maternal intake of goldthread during the first trimester increases the risk of congenital malformations of the central nervous system (15129).

LACTATION: LIKELY UNSAFE
when used orally. Berberine and other harmful constituents can be transferred to the infant through breast milk (2589).

(Read more about GOLDTHREAD)

POSSIBLY SAFE ...when used orally and appropriately (12). ...when used topically and appropriately (12). A lotion containing 5% heart's ease extract has been safely used in a study lasting up to 4 weeks (67372).

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

(Read more about HEART'S EASE)

POSSIBLY SAFE ...when used orally and appropriately, short term. Rehmannia root extract 4 grams daily or rehmannia leaf extract 800 mg daily has been used with apparent safety for 8 weeks in clinical studies (93660,93662).

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

(Read more about REHMANNIA)

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

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

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

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

(Read more about RHUBARB)

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)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bupleurum might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro research suggests that saikosaponins, constituents of bupleurum, can inhibit platelet aggregation (3159,3156).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bupleurum might decrease the effects of antidiabetes drugs.  Details Animal research suggests that saikosaponins, constituents of bupleurum, can increase blood glucose (37402,37403).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, bupleurum might decrease the effects of immunosuppressants.  Details In vitro and animal research suggests that bupleurum might stimulate immune function (2598,3160,3161).

(Read more about BUPLEURUM)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dong quai may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs; however, research is conflicting.  Details Animal studies suggest that dong quai has antithrombin activity and inhibits platelet aggregation due to its coumarin components (6048,10057,96137). Additionally, some case reports in humans suggest that dong quai can increase the anticoagulant effects of warfarin (3526,6048,23310,48439). However, clinical research in healthy adults shows that taking 1 gram of dong quai root daily for 3 weeks does not significantly inhibit platelet aggregation or cause bleeding (96137). Until more is known, use dong quai with caution in patients taking antiplatelet/anticoagulant drugs.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dong quai may reduce the effects of estrogens.  Details Dong quai has estrogenic effects (6180,7860,15108,15535,48459). Theoretically, concomitant use of large amounts of dong quai might interfere with hormone replacement therapy due to competition for estrogen receptors.

WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Dong quai may increase the risk of bleeding when used with warfarin.  Details Case reports suggest that concomitant use of dong quai with warfarin can increase the anticoagulant effects of warfarin and increase the risk of bleeding (3526,6048,23310,48439). In one case, after 4 weeks of taking dong quai 565 mg once or twice daily, the international normalized ratio (INR) increased to 4.9. The INR normalized 4 weeks after discontinuation of dong quai (3526).

(Read more about DONG QUAI)

(Read more about GENTIAN)

(Read more about GOLDTHREAD)

(Read more about HEART'S EASE)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, honeysuckle might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro research shows that polyphenols extracted from honeysuckle can inhibit platelet aggregation (12610).

(Read more about HONEYSUCKLE)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rehmannia might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal research shows that rehmannia may have hypoglycemic effects (15061,93668).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rehmannia might increase the risk of hypotension when taken with antihypertensive drugs.  Details Animal research shows that rehmannia may have hypotensive effects. Laboratory research shows that formulations of dried and processed rehmannia root inhibit angiotensin-converting enzyme (ACE) (104272).

(Read more about REHMANNIA)

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

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

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

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

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

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

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

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

(Read more about RHUBARB)

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)

General ...Orally, bupleurum seems to be well tolerated. However, most research has evaluated bupleurum in combination with other ingredients; the adverse effects of bupleurum when used alone are unclear.

Gastrointestinal ...Orally, a specific bupleurum-containing combination product (sho-saiko-to) has been reported to cause nausea, anorexia, and abdominal fullness (37391). It is unclear if these adverse effects are due to bupleurum, other ingredients, or the combination.

Hepatic ...Orally, a specific bupleurum-containing combination product (sho-saiko-to) has been associated with at least 24 reported cases of hepatotoxicity (92575). It is unclear if these adverse effects are due to bupleurum, other ingredients, or the combination.

Neurologic/CNS ...Orally, a specific bupleurum-containing combination product (sho-saiko-to) has been reported to cause fatigue and paresthesia (37391). It is unclear if these adverse effects are due to bupleurum, other ingredients, or the combination.

Pulmonary/Respiratory ...Orally, combination products containing bupleurum have been reported to cause eosinophilic pneumonia (354), pulmonary edema (361), and multiple cases of pneumonitis (355,356,357,37404). A specific combination product (sho-saiko-to), used in combination with interferon-alpha in patients with chronic active hepatitis, has also been associated with multiple cases of pneumonitis (358,359,360). It is unclear if these adverse effects are due to bupleurum, other ingredients, or the combination.

(Read more about BUPLEURUM)

General ...Orally, dong quai is generally well-tolerated.
Most Common Adverse Effects:
Orally: Burping and flatulence.
Intravenously: Headache.

Cardiovascular ...Orally, dong quai might cause hypertension; according to one case report, a parent and breastfed infant experienced hypertension (195/85 mmHg and 115/69 mmHg, respectively) after the parent consumed a soup containing dong quai root (48428).

Dermatologic ...Dong quai contains psoralens that may cause photosensitivity and photodermatitis (10054,10057,48461).

Endocrine ...In a case report, a male developed gynecomastia after ingesting dong quai tablets (48504).

Gastrointestinal ...Orally, burping and gas may occur with dong quai (738).

Hematologic ...In one case report, a 55-year-old female with protein S deficiency and systemic lupus erythematosus (SLE) had temporary vision loss in the left eye from hemiretinal vein thrombosis three days after taking a phytoestrogen preparation containing dong quai 100 mg, black cohosh 250 mg, wild Mexican yam 276 mg, and red clover 250 mg (13155). It is unclear if dong quai contributed to this event.

Neurologic/CNS ...Dong quai given orally or by injection may be associated with headache (738,48438).

Oncologic ...Dong quai contains constituents that are carcinogenic; however, whether these constituents are present in concentrations large enough to cause cancer with long-term or high-dose use is unknown (7162).

Pulmonary/Respiratory ...A pharmacist experienced allergic asthma and rhinitis after occupational exposure to dong quai and other herbs (48435).

(Read more about DONG QUAI)

General ...Orally, gentian root, in combination with other herbs, seems to be generally well tolerated (95907). Side effects reported in clinical studies include gastrointestinal discomfort and allergic skin reactions (374,379). There is insufficient reliable information available about the adverse effects of gentian when taken as a medicine alone.

Gastrointestinal ...Orally, gentian root, in combination with other herbs, has been reported to cause gastrointestinal adverse effects (374,379). Gastrointestinal intolerance occurred in patients with cancer-associated anorexia who took gentian tincture 1 mL three times daily, in conjunction with turmeric 1 gram and ginger 1 gram twice daily, for 14 days. Six of 17 patients discontinued the regimen due to nausea, 3 due to vomiting, 2 due to diarrhea, and 2 due to bloating. It is unclear if this gastrointestinal intolerance was caused by gentian, the other herbs, or the patients' predisposing conditions (96263).

Immunologic ...Orally, gentian root, in combination with other herbs, has been reported to cause allergic skin reactions (374,379). It is unclear if these reactions were caused by gentian, the other herbs, or the combination.

(Read more about GENTIAN)

General ...No adverse effects have been reported in adults. However, a thorough evaluation of safety outcomes has not been conducted.

(Read more about GOLDTHREAD)

General ...Orally, heart's ease seems to be generally well tolerated (12). It has caused hemolysis in a nine-month-old infant with glucose-6-phosphate-dehydrogenase (G6PD) deficiency (11324).

Hematologic ...Orally, heart's ease boiled extract has caused hemolysis in a nine-month-old infant with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. The methyl ester of salicylic acid, a constituent of heart's ease, is hypothesized to be responsible for this effect (11324).

(Read more about HEART'S EASE)

General ...Orally, honeysuckle seems to be well tolerated. No adverse effects have been reported. There is insufficient reliable information available about the safety of honeysuckle when used topically. However, a thorough evaluation of safety outcomes has not been conducted.

Immunologic ...Topically, applying honeysuckle to the skin has been associated with contact dermatitis in a case report (12611). Orally, a case of biopsy-confirmed allergic drug eruption is reported in a young adult male after taking honeysuckle granules 30 grams over a 24-hour period. Symptoms resolved with discontinuation of honeysuckle and 2-weeks of antihistamine and glucocorticoid therapy (112866).

(Read more about HONEYSUCKLE)

General ...Orally, rehmannia seems to be well tolerated.

(Read more about REHMANNIA)

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

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

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

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

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

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

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

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

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

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

(Read more about RHUBARB)

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).

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