Dong Quai and Royal Jelly [Discontinued] by GNC

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

• Menopausal symptoms. Several clinical studies suggest that oral royal jelly, taken alone or in combination with other ingredients, modestly improves menopausal symptoms. It is unclear if topical royal jelly is beneficial for this use. Details: One clinical study in postmenopausal patients shows that taking royal jelly 1000 mg daily for 8 weeks reduces menopausal symptom scores by around 30% when compared with placebo (102527). Other small clinical studies show that taking one to two capsules of a specific combination product containing royal jelly and flower pollen (Melbrosia) daily for 12 weeks reduces menopausal symptoms and improves feelings of well-being when compared with baseline or placebo (18064,71956,72005). Another clinical trial in postmenopausal patients shows that taking two capsules of a specific combination product containing royal jelly, evening primrose oil, damiana, and ginseng (Lady 4) daily for 4 weeks decreases self-rated menopausal symptoms when compared with placebo (21003). Topical royal jelly has also been evaluated. A small clinical study in postmenopausal adults shows that applying vaginal cream containing royal jelly 15% daily for 12 weeks improves quality of life, sexual problems, and urinary problems similarly to vaginal estrogen cream 0.625 mg. However, estrogen cream improves vaginal atrophy better than royal jelly (92884).

POSSIBLY INEFFECTIVE

• Allergic rhinitis (hay fever). Oral royal jelly does not appear to prevent or treat symptoms of allergic rhinitis in children. Details: A clinical trial in children 5-16 years of age with allergic rhinitis shows that taking a specific royal jelly product (Bidro) 150 mg twice daily for 3-6 months before and during pollen season does not prevent or treat nasal congestion, sneezing, or eye discomfort when compared with placebo (71968).
• Diabetes. Oral royal jelly does not appear to improve glycemic control in patients with type 2 diabetes. Details: Most clinical research in patients with type 2 diabetes, along with a meta-analysis of five small clinical trials including patients with or without type 2 diabetes, shows that taking royal jelly 0.5-6 grams daily for 4-8 weeks does not improve markers of glycemic control such as fasting plasma glucose and glycated hemoglobin (HbA1c) (92879,92880,92881,102529).
• Physical performance. Oral royal jelly does not appear to improve physical performance in elderly nursing home residents. Details: A clinical trial in elderly nursing home residents shows that taking royal jelly 1.2 grams or 4.8 grams daily for one year does not improve hand grip strength, walking, or ability to stand on one leg when compared with placebo (95870).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. Although there has been interest in using topical royal jelly for androgenic alopecia, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Atherosclerosis. Although there has been interest in using oral royal jelly for atherosclerosis, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Athletic performance. Oral royal jelly has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Two small clinical trials in elite male swimmers and runners show that taking royal jelly 400 mg and coenzyme Q10 60 mg daily for 10 days does not improve high-intensity interval training performance when compared with placebo (109992,109993). These studies were small and may not have been adequately powered to detect a difference between groups.
• Cancer-related fatigue. It is unclear if oral royal jelly is beneficial for improving cancer-related fatigue. Details: A small clinical study in patients with solid (nonhematologic) malignancies shows that taking 5 mL of processed honey and royal jelly twice daily for 4 weeks reduces fatigue when compared with 5 mL of honey alone (92877).
• Chemotherapy-induced acral erythema. It is unclear if oral royal jelly is beneficial for preventing acral erythema from tyrosine kinase inhibitors (TKIs). Details: One small clinical trial in patients receiving TKI therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months does not reduce the risk of acral erythema when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference between groups.
• Chemotherapy-induced hepatotoxicity. It is unclear if oral royal jelly is beneficial for preventing hepatotoxicity from tyrosine kinase inhibitors (TKIs). Details: One small clinical trial in patients receiving TKI therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months does not reduce the risk of hepatotoxicity when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference between groups.
• Chemotherapy-induced nephrotoxicity. It is unclear if oral royal jelly is beneficial for preventing chemotherapy-induced nephrotoxicity. Details: A small clinical study in patients receiving two cycles of cisplatin therapy shows that taking royal jelly capsules daily may attenuate increases in serum creatinine and urea levels when compared with placebo. However, it is unclear if this effect is clinically significant; the increased levels that occurred in the placebo group were still within normal limits (95871). The validity of these results is also limited by the short study duration and lack of statistical comparison between groups. Another small clinical trial in patients receiving tyrosine kinase inhibitor therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months does not reduce the risk of kidney dysfunction when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference between groups.
• Chemotherapy-related fatigue. It is unclear if oral royal jelly is beneficial for preventing fatigue from tyrosine kinase inhibitors (TKIs). Details: One small clinical trial in patients receiving TKI therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months reduces the frequency of chemotherapy-related fatigue when compared with placebo (105773,105774).
• Cognitive impairment. Oral royal jelly has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in elderly patients with mild cognitive impairment shows that taking a specific combination product (Memo, Pharco Pharmaceuticals), which contains natural lyophilized royal jelly 750 mg, ginkgo leaf extract 120 mg, and Panax ginseng root extract 150 mg, daily for 4 weeks improves cognitive ability when compared with placebo (89712).
• Coronavirus disease 2019 (COVID-19). Oral royal jelly has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults without diabetes in Iran hospitalized with moderately severe COVID-19 receiving corticosteroids shows that taking a specific combination supplement (Tang Forte, HealthAid) containing royal jelly extract 350 mg and vitamin E 2 mg daily for 7 days does not improve markers of the clinical course of COVID-19, such as oxygen saturation or length of hospital stay, when compared with placebo (114535). However, this study may not have been adequately powered to detect a difference between groups. It is unclear if this effect is due to royal jelly, other ingredients, or the combination.
• Diabetic foot ulcers. Small clinical studies suggest that topical application of royal jelly plus panthenol may improve healing of diabetic foot ulcers. It is unclear if topical royal jelly alone is beneficial for this use. Details: One small clinical study shows that applying royal jelly 5% to a wound after conventional cleansing and debriding three times weekly for 3 months does not improve the healing of diabetic foot ulcers when compared with placebo (92882). However, other small clinical studies show that applying 1-3 grams of a specific combination ointment (Pedyphar) containing royal jelly and panthenol after conventional cleansing and debriding procedures twice weekly for up to 6 months may improve the healing of diabetic foot ulcers (71980,102526). In one of these studies, the rate of complete healing of life-threatening ulcers was 2.7-fold greater with this combination ointment when compared with panthenol alone (102526). Possible reasons for these discrepancies include the use of combination versus single ingredient ointments and the duration of treatment.
• Dry eye. It is unclear if oral royal jelly is beneficial in patients with dry eye. Details: A small clinical trial in Japanese patients with dry eye shows that taking enzyme-treated royal jelly 2.4 grams daily for 8 weeks does not improve tear stability or dry eye symptoms when compared with placebo (95869).
• Fractures. Although there has been interest in using oral royal jelly for healing of fractures, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Hepatitis. Although there has been interest in using oral royal jelly for hepatitis, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Male infertility. Intravaginal application of royal jelly has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in couples experiencing infertility due to asthenozoospermia shows that applying a saline solution containing royal jelly 3 grams, Egyptian bee honey 100 grams, and bee bread 1 teaspoon intravaginally before or after intercourse, starting one day after menstruation and continuing for 2 weeks, can increase the rate of pregnancy when compared with intrauterine insemination (55131). It is unclear if this effect is due to royal jelly, other ingredients, or the combination.
• Obesity. It is unclear if oral royal jelly is beneficial for reducing body weight in patients who are overweight or obese. Details: One small clinical study in overweight patients with type 2 diabetes shows that taking fresh royal jelly 1 gram daily for 8 weeks reduces body weight by around 2 kg and body mass index (BMI) by around 0.7 kg/m², as well as carbohydrate and total energy intake, when compared with placebo. However, the improvement is modest and may not be clinically significant (92878). Another small clinical study in overweight adults shows that taking royal jelly 1000 mg daily for 8 weeks does not reduce body weight, BMI, or appetite when compared with placebo (102528). However, this study may have been inadequately powered to detect a difference in these outcomes.
• Oral mucositis. It is unclear if oral royal jelly is beneficial for preventing or treating oral mucositis in patients receiving radiotherapy and/or chemotherapy. Details: One small clinical trial in patients receiving chemotherapy and radiotherapy shows that swishing and swallowing royal jelly 1 gram in two divided doses daily, in addition to standard rinses with benzydamine and nystatin, improves healing time of mild or moderate oral mucositis when compared with standard rinses alone (95867).
• Osteoporosis. It is unclear if oral royal jelly is beneficial in patients with osteoporosis. Details: A small clinical trial in postmenopausal adults shows that taking royal jelly powder 1000 mg, equivalent to 3000 mg of fresh royal jelly, daily for 6 months maintains bone mineral density (BMD) in the proximal femur and lumbar spine, while patients taking placebo saw significant reductions in lumbar spine BMD. Also, markers of bone turnover were significantly reduced with placebo, while significant changes in these markers were lacking in patients taking royal jelly (105775). It is unclear whether these findings can be generalized to patients with documented osteoporosis.
• Peptic ulcers. Although there has been interest in using oral royal jelly for peptic ulcers, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Premenstrual syndrome (PMS). It is unclear if oral royal jelly, taken alone or in combination with other ingredients, is beneficial in patients with PMS. Details: A small clinical study in healthy college students shows that taking royal jelly 1 gram daily starting on the first day of menstruation and continuing for two consecutive menstrual cycles improves PMS symptoms when compared with placebo (95873). However, methodological flaws associated with the study limit the validity of these results. A small clinical study shows that taking a specific combination product (Femal, Natumin Pharma), providing royal jelly 12 mg, bee pollen extract 72 mg, and bee pollen plus pistil extract 240 mg, twice daily over 2 menstrual cycles seems to decrease some symptoms of PMS including irritability, weight increases, and edema (12008). It is unclear if these effects are due to royal jelly, other ingredients, or the combination.
• Renal cell carcinoma. It is unclear if oral royal jelly is beneficial in patients with renal cell carcinoma. Details: One small clinical trial in patients receiving tyrosine kinase inhibitor (TKI) therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months reduces tumor size, improves chemotherapy-related fatigue and anorexia, and reduces the need for dose reduction or the discontinuation of therapy when compared with placebo (105773,105774). Royal jelly does not seem to reduce other TKI-related adverse effects, including gastrointestinal symptoms, oral mucositis, acral erythema, anemia, hepatotoxicity, or nephrotoxicity, when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference in these outcomes. More evidence is needed to rate royal jelly for these uses.

(Read more about ROYAL JELLY)

POSSIBLY EFFECTIVE

• Mastalgia. Meta-analyses of small clinical studies show that vitex agnus-castus moderately reduces breast pain due to cyclic mastalgia. Details: Two small meta-analyses of low-to-moderate quality clinical studies in patients with cyclic mastalgia show that taking vitex agnus-castus moderately reduces breast pain when compared with placebo (101981,111753). The validity of these findings is limited by the heterogeneity of the included studies. Doses of vitex agnus-castus dried fruit extract range from 3.2-40 mg daily, for 2-6 months (90617,96250,101981,111753). Vitex agnus-castus is commonly used in proprietary products, alone or in combination with other herbs (Agnucaston/Cyclodynon, Bionorica AG, Femicur, Mastodynon, Bionorica AG, Monoselect Agnus, ZE 440) (13395).
• Premenstrual syndrome (PMS). Clinical research shows that vitex agnus-castus produces modest improvements in PMS symptoms. Details: Clinical research shows that taking vitex agnus-castus fruit extract orally for 2-6 menstrual cycles seems to reduce symptoms of PMS, especially breast pain or tenderness (mastalgia), edema, constipation, irritability, depressed mood, anxiety, anger, and headache (7055,7076,7078,7079,13394,15065,41483,41489,41490,41494,90619,101981). Doses of fruit extracts have varied from 3.5-40 mg daily, usually for 2-3 menstrual cycles (7055,7076,7078,7079,15065,41483,41489,41490,90619,96435). A meta-analysis of the available clinical research, including 17 studies involving 2,401 patients, shows that taking vitex agnus-castus is comparable to fluoxetine or oral contraceptives, and modestly more effective than placebo, for reducing the symptoms of PMS. A sub-group analysis indicates that efficacy is not impacted by the dose or form used, although the dried powdered berries appear to be ineffective. The low quality of the included studies and the high level of bias and heterogeneity limit the validity of these findings (96435). Another meta-analysis limited to three randomized controlled trials shows that taking vitex agnus-castus increases the likelihood of PMS symptom remission by 2.6-fold over placebo (101979). Some clinical studies have used a specific dried extract of vitex agnus-castus fruit (Agnolyt, Madaus AG) (7076). Other studies used a specific fruit extract known as Ze 440 (Prefemin, Zeller AG), which is standardized to casticin content (7078,90619). Additional studies have used the fruit extract BNO 1095 (Agnucaston/Cyclodynon, Bionorica AG) (15065,41483,41489,41490).

POSSIBLY INEFFECTIVE

• Fractures. Limited evidence suggests that vitex agnus-castus does not improve fracture healing rates. Details: Clinical research shows that taking a specific vitex agnus-castus dried fruit extract (Agnugol, Goldaru Pharmacy Company) 4 mg, alone or in combination with magnesium oxide (Nature Made Company) 250 mg, daily for 8 weeks does not improve long bone fracture healing when compared with placebo (90618).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using oral vitex agnus-castus for acne, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Aging skin. Vitex agnus-castus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical trial in postmenopausal adults with wrinkles shows that taking one capsule orally daily of a combination of vitex agnus-castus 400 mg, evening primrose oil 500 mg, soy isoflavones 100 mg, and black cohosh 520 mg (Estosalus, Max Biocare Pty Ltd) for 12 weeks improves skin elasticity, skin smoothness, and wrinkle density scores when compared with placebo (109440).
• Amenorrhea. Although there is interest in using oral vitex agnus-castus for amenorrhea, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Anxiety. Although there is interest in using oral vitex agnus-castus for anxiety, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Benign prostatic hyperplasia (BPH). Although there is interest in using oral vitex agnus-castus for BPH, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Dementia. Although there is interest in using oral vitex agnus-castus for dementia, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Dysmenorrhea. It is unclear if oral vitex agnus-castus is beneficial in patients with dysmenorrhea. Details: Preliminary clinical research in patients with primary dysmenorrhea shows that taking a specific vitex agnus-castus extract (Agnucaston, Bionorica AG) daily for 3 months reduces pain, as measured on a visual analog scale, similarly to ethinyl estradiol 0.03 mg / drospirenone 3 mg (Yasmin) taken daily (104975).
• Fibrocystic breast disease. Although there is interest in using oral vitex agnus-castus for fibrocystic breast disease, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Hyperprolactinemia. Although there is interest in using oral vitex agnus-castus for hyperprolactinemia, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Infertility. It is unclear if oral vitex agnus-castus is beneficial for female infertility. Details: Preliminary clinical research in infertile females with oligomenorrhea or amenorrhea shows that taking homeopathic vitex agnus-castus (Phyto Hypophyson L, Steierl-Pharma GmbH) 50 drops orally three times daily for 3 months does not increase the chance of getting pregnant (41470). Also, one small clinical study in those with infertility due to secondary amenorrhea or luteal insufficiency shows that taking a vitex agnus-castus preparation (Mastodynon, Bionorica GmbH, Neumarkt/Opf.) 30 drops twice daily for at least 3 months does not increase the chance of pregnancy when compared with placebo, although the study was likely inadequately powered to detect a difference (7077).
• Insect repellent. Limited research suggests that topical vitex agnus-castus has insect repellent activity. Details: Preliminary clinical research shows that applying a carbon dioxide extract of vitex agnus-castus seeds seems to repel ticks and fleas for 6 hours, mosquitoes for 3-8 hours, and biting flies for 3 hours (13396). It is unclear how this compares with commonly used insect repellants.
• Insomnia. Although there is interest in using oral vitex agnus-castus for insomnia, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Lactation. Although there is interest in using oral vitex agnus-castus for stimulating lactation, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Menopausal symptoms. Clinical research suggests that vitex agnus-castus can relieve some menopausal symptoms; however, most research uses vitex agnus-castus in combination with other treatments. Details: Clinical research shows that taking vitex agnus-castus extract 15 mg twice daily for 8 weeks improves some menopausal symptoms, including anxiety and vasomotor dysfunction, by 76% and 88%, respectively, when compared with baseline. However, there was no effect on depression or sexual dysfunction (101980). Vitex agnus-castus has also been studied as a component of combination products. Preliminary clinical research shows that taking a combination of vitex agnus-castus, equivalent to 1000 mg dried fruit, black seed powder 500 mg, and citalopram 20 mg daily for 8 weeks reduces vasomotor, psychosocial, and physical symptoms of menopause when compared with citalopram alone (100325). Other preliminary clinical research shows that taking one capsule orally daily of a combination of vitex agnus-castus 400 mg, evening primrose oil 500 mg, soy isoflavones 100 mg, and black cohosh 520 mg (Estosalus, Max Biocare Pty Ltd) for 12 weeks moderately reduces the severity of hot flashes, sweating, sleep problems, depressed mood, and irritability when compared with placebo. There was no effect on plasma lipids, joint discomfort, anxiety, exhaustion, or sexual problems (105102). It is unclear if these effects are due to vitex agnus-castus, other ingredients, or the combination.
• Menorrhagia. It is unclear if oral vitex agnus-castus is beneficial in patients with menorrhagia. Details: A meta-analysis of two moderate quality clinical trials in patients who had heavy menstrual periods shows that taking vitex agnus-castus does not reduce menstrual bleeding over the next 1-2 menstrual cycles when compared with placebo (101982). However, preliminary clinical research in patients using an intrauterine device (IUD) shows that taking vitex agnus-castus three times daily for 8 days, starting on the first day of menstruation, and repeated for four consecutive menstrual cycles, reduces the amount of bleeding by approximately 48% when compared with baseline. This reduction was similar to the effects of mefenamic acid 250 mg daily after 4 months, although treatment with mefenamic acid was superior during the first three months (90620).
• Migraine headache. Although there is interest in using oral vitex agnus-castus for migraine headache, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Polycystic ovary syndrome (PCOS). Vitex agnus-castus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with oligomenorrhea due to PCOS shows that taking a traditional combination product (Aslagh) containing equivalent amounts of essential oils of vitex agnus-castus fruit, fennel, and wild carrot seeds orally daily for 3 months, either alone or in combination with metformin, improves rates of menstrual bleeding and menstrual cyclicity similarly to metformin alone. All three groups experienced a significant improvement from baseline. Aslagh was taken as two, 500-mg capsules twice daily, except during menses; metformin was titrated over one week to a dose of 500 mg three times daily (108974).
• Premenstrual dysphoric disorder (PMDD). Limited evidence suggests that vitex agnus-castus might improve symptoms of PMDD. Details: In a clinical trial, vitex agnus-castus 20-40 mg daily for 8 weeks was similar to fluoxetine 20-40 mg daily for relieving symptoms of PMDD. About 58% of patients responded to vitex agnus-castus, compared to about 68% of patients taking fluoxetine. Vitex agnus-castus was more effective for physical symptoms such as breast tenderness, swelling, cramps, and food cravings (12207,41493).
• Rheumatoid arthritis (RA). Although there is interest in using oral vitex agnus-castus for RA, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Sexual dysfunction. It is unclear if oral vitex agnus-castus is beneficial in patients with sexual dysfunction. Details: Preliminary clinical research in healthy females under 44 years of age with sexual dissatisfaction shows that taking a specific vitex agnus-castus product (Agnugol, Goldaru Herbal Pharmaceutical Company) 3.2-4.8 mg orally once daily for 16 weeks modestly improves scores of sexual satisfaction, function, arousal, and desire when compared with placebo (109437). Additionally, a moderate-sized clinical study in females 50-69 years old with sexual dysfunction conducted in Iran shows that taking vitex agnus-castus 40 drops daily for 8 weeks improves sexual dysfunction scores from mild dysfunction to no dysfunction at 6 and 8 weeks when compared with placebo but does not improve scores at 4 weeks (112361). More evidence is needed to rate the effectiveness of vitex agnus-castus for these uses.

(Read more about VITEX AGNUS-CASTUS)

POSSIBLY INEFFECTIVE

• Menopausal symptoms. Topical wild yam does not seem to improve menopausal symptoms. Details: Wild yam applied topically as a cream in menopausal patients for 3 months appears to be no better than placebo for relieving vasomotor symptoms, such as hot flashes and night sweats. It also does not appear to change serum follicle stimulating hormone (FSH), estradiol, or progesterone levels (10989).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cognitive function. It is unclear if oral wild yam is beneficial for improving cognitive function in healthy adults. Details: Preliminary clinical research in healthy adults shows that taking a specific wild yam extract (Diopower 15, Anti-Aging Pro Corporation) orally, 50 mg (containing diosgenin 8 mg) daily for 12 weeks, modestly improves overall measures of cognitive function and semantic fluency when compared with placebo (96724).
• Dysmenorrhea. Although there is interest in using oral or topical wild yam for dysmenorrhea, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Gallbladder disease. Although there is interest in using oral wild yam for gallbladder disease, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Infertility. Although there is interest in using oral or topical wild yam for infertility, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Osteoporosis. Although there is interest in using oral wild yam for osteoporosis, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Postmenopausal conditions. Although there is interest in using oral wild yam for postmenopausal conditions, there is insufficient reliable information about the clinical effects of wild yam for these conditions.
• Premenstrual syndrome (PMS). Although there is interest in using oral wild yam for PMS, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Rheumatoid arthritis (RA). Although there is interest in using oral wild yam for RA, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Sexual dysfunction. Although there is interest in using oral wild yam for sexual dysfunction, there is insufficient reliable information about the clinical effects of wild yam for this condition. More evidence is needed to rate wild yam for these uses.

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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.

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POSSIBLY SAFE ...when used orally and appropriately, short-term. Royal jelly 1-4.8 grams daily for up to 1 year has been used in clinical research without reported adverse effects (95869,95870,102527,102528,105773,105774)....when used topically and appropriately for up to 6 months (71980,102526).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately for up to 6 months. A specific royal jelly product (Bidro) 150 mg twice daily has been used with apparent safety for 3-6 months in children 5-16 years of age (71968).

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

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LIKELY SAFE ...when the fruit extract is used orally and appropriately, short-term. Vitex agnus-castus fruit extract has been used safely in studies at doses up to 40 mg daily, for up to 3 months (7055,7076,7077,7078,7079,12207,13393,15065,90617,90618,96435). There is insufficient reliable information available about the safety of vitex agnus-castus seeds when used orally or topically.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally. Theoretically, the hormonal effects of vitex agnus-castus might adversely affect pregnancy or lactation (10979,11456,13393,109439). Animal research shows that taking vitex agnus-castus fruit extract when planning to become pregnant or during pregnancy may increase the risk of infertility, low fetal body weight, abortion, and stillbirth (109439); avoid using.

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POSSIBLY SAFE ...when used orally. A dose of 50 mg (containing 8 mg diosgenin) has been used with apparent safety for 12 weeks (12,96724). ...when used topically. A wild yam cream has been used with apparent safety for 3 months (10989).

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

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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).

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ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, royal jelly might increase the risk of hypotension when taken with antihypertensive drugs.  Details Animal research suggests that royal jelly might lower blood pressure (71982,71963).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Royal jelly might increase the risk of bleeding when taken with warfarin.  Details In one case, an 87-year-old male who was previously stabilized on warfarin developed hematuria and was found to have an INR of 7.29 after taking a royal jelly supplement for one week (14303).

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ANTIPSYCHOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, vitex agnus-castus could interfere with the activity of antipsychotic drugs.  Details Vitex agnus-castus might interfere with the action of dopamine antagonists such as antipsychotic drugs due to its dopamine agonist effects (7014,7015).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, vitex agnus-castus could interfere with oral contraceptives.  Details Vitex agnus-castus might interfere with the efficacy of oral contraceptives due to possible hormone modulating activity (10979,11456).

DOPAMINE AGONISTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, vitex agnus-castus could interfere with dopamine agonists.  Details Vitex agnus-castus might potentiate the actions of dopaminergic agonists due to possible dopaminergic effects (10122).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, vitex agnus-castus could interfere with the activity of estrogens.  Details Vitex agnus-castus has hormone modulating activity that can interfere with the efficacy of hormone replacement therapy (10979,11456).

METOCLOPRAMIDE (Reglan) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dopaminergic effects of vitex agnus-castus could interfere with metoclopramide.  Details Vitex agnus-castus might interfere with the action of dopamine antagonists such as metoclopramide due to its possible dopaminergic effects (7014,7015).

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ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, wild yam might increase or decrease the effects of estrogen.  Details Wild yam root shows estrogenic and anti-estrogenic effects in vitro (6180,70411,96723,96725). Theoretically, wild yam might interfere with hormone therapy.

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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).

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General ...Orally and topically, royal jelly seems to be well tolerated.
Most Common Adverse Effects:
Orally: Dyspnea, eczema, oral allergy syndrome, pruritus, and urticaria in people with a history of asthma or atopy.
Topically: Contact dermatitis and skin irritation.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis, status asthmaticus, and death in people with a history of asthma or atopy.

Gastrointestinal ...There is one case report of hemorrhagic colitis with abdominal pain, bloody diarrhea with concomitant hemorrhagic and edematous mucosa of the sigmoid colon after ingestion of royal jelly. Symptoms resolved within 2 weeks following discontinuation of royal jelly and conservative treatment (3516).

Immunologic ...In people with a history of atopy or asthma, royal jelly taken orally appears to cause a high rate of allergic symptoms including pruritus, urticaria, eczema, eyelid and facial edema, conjunctivitis, rhinorrhea, dyspnea, oral allergy syndrome, and asthma (7314,7315,7316,10623,95872). In severe cases, royal jelly can cause status asthmaticus, anaphylaxis, and death (792,7315,7316,10623,10624,108511). Allergic symptoms are associated with IgE-mediated hypersensitivity reactions (3513,10623).
Topically, skin irritation, exacerbation of dermatitis, or contact dermatitis may occur (791).
From occupational exposure, royal jelly can cause allergic rhinoconjunctivitis and asthma (95868).

Neurologic/CNS ...There is one report of dizziness in a patient who took a combination product containing royal jelly, bee pollen extract, and a bee pollen plus pistil extract (12008).

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General ...Orally, vitex agnus-castus is generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, fatigue, headache, insomnia, irregular menstruation, nausea, skin irritation, stomach pain, vomiting.

Dermatologic ...Orally, skin conditions such as itching, irritation, urticaria, rash, acne, eczema, and hair loss have been reported (7055,7076,7078,7079,12207,13393,15065,90617,90619,101981).

Gastrointestinal ...Orally, gastrointestinal upset or pain, diarrhea, and nausea and vomiting, have been reported (7079,12207,13393,15065,90620,101981,101982). In one clinical trial, a single patient reported persistent gastroenteritis while taking vitex agnus-castus (7076). Orally, development of a bezoar resulting in colonic obstruction is described in a 63-year-old male who consumed an unknown amount of vitex agnus-castus seeds (111752).

Genitourinary ...Orally, irregular or prolonged menstrual bleeding has been reported (7055,7079,12207,13393,15065,41489,41490,95326).

Hematologic ...Orally, nosebleed has been reported in a single patient in a clinical trial (7079).

Immunologic ...Orally, multiple abscesses have been reported in a single patient (7055).

Neurologic/CNS ...Orally, headache, fatigue, and insomnia (7076,7078,12207,13393,13395,15065), confusion (90617), and vertigo (7079) have been reported.

Other ...Orally, weight gain has been reported (12207,13393,15065).

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General ...Orally, wild yam is generally well tolerated.
Most Common Adverse Effects:
Orally: Fever, headache, upset stomach, and vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.

Gastrointestinal ...Orally, wild yam can cause upset stomach and vomiting, especially at higher doses (12,86450).

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 3 days after taking a combination phytoestrogen product containing wild yam 276 mg, dong quai 100 mg, red clover 250 mg, and black cohosh 250 mg (13155). It is unclear if wild yam contributed to this event.

Immunologic ...There are three case reports of anaphylaxis after ingestion of cooked wild yam (96722).

Neurologic/CNS ...Orally, wild yam can cause headache and fever, especially at higher doses (86450).

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