Bioglan MenoPause Day & NIght Formulas by PharmaCare Laboratories Pty Ltd

POSSIBLY EFFECTIVE

• Generalized anxiety disorder (GAD). Oral ashwagandha may modestly improve symptoms of anxiety in patients with GAD. Details: Clinical practice guidelines from the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) provisionally recommend ashwagandha root extract at doses of 300-600 mg, standardized to 5% withanolides, daily as monotherapy or adjunctive therapy in patients with GAD. This recommendation is based on a review of three preliminary clinical trials with consistent results (110318). Two of these studies are described below. A small clinical trial in patients with GAD who are taking selective serotonin reuptake inhibitors (SSRIs) shows that taking ashwagandha 1 gram daily for 6 weeks reduces symptoms of anxiety by 48%, compared with a 27% reduction in patients taking placebo. Furthermore, by the end of treatment, 72% of patients taking ashwagandha were determined to have mild symptoms of GAD, compared with only 32% of those taking placebo (102687). Another preliminary clinical trial in patients aged 16 years and older with GAD shows that taking ashwagandha root powder granules 4 grams three times daily for 60 days moderately improves anxious mood in 58% of patients, compared with no moderate improvement in the placebo group. Mild improvement occurred in 82% of patients in the placebo group and 40% of patients in the ashwagandha group (90654).
• Insomnia. Oral ashwagandha may modestly improve sleep in patients with insomnia or non-restorative sleep. Details: A small meta-analysis in patients with insomnia and healthy patients shows that taking a specific ashwagandha root extract (KSM-66, Ixoreal Biomed) 250-600 mg daily or a specific root and leaf extract (Shoden, Arjuna Natural) 120 mg daily for 6-12 weeks modestly improves overall sleep, as well as sleep quality, sleep latency, total sleep time, wake time after sleep onset, and sleep efficiency, when compared with placebo. Effects were more pronounced in those with insomnia, with doses of at least 600 mg daily, and with treatment durations of at least 8 weeks (106784). These findings may be limited by heterogeneity of the included studies. In patients with non-restorative sleep, clinical research shows that taking a specific ashwagandha extract (Shoden, Arjuna Natural Private Ltd) 125 mg daily for 6 weeks increases sleep quality by 72%, compared with an improvement of 29% in patients taking placebo. Small to moderate improvements also occurred in total sleep time, sleep latency, and number of times awake (103476).
• Stress. Oral ashwagandha seems to help reduce stress and may also reduce stress-related weight gain. Details: A meta-analysis of seven small clinical studies in healthy adults, patients with chronic stress, or patients with psychiatric conditions shows that taking ashwagandha 240-1000 mg daily for 8-12 weeks improves stress when compared with placebo (109587). Clinical studies included in this meta-analysis that evaluated adults with chronic stress show that taking specific ashwagandha root extracts 240 mg daily (Shoden, Arjuna Natural Ltd.) or 300 mg twice daily (KSM-66, Ixoreal Biomed) for 60 days reduces perceived stress levels by 30% to 44% and decreases cortisol levels by 22% to 28% when compared with baseline. These improvements remain significant when compared with the changes seen for patients treated with placebo (90652,95617,101816,102682). In adults reporting moderate to high stress levels, clinical research shows that treatment with specific slow-release capsules containing another ashwagandha root extract (Prolanza), 300 mg daily for 90 days, lowers perceived stress scores and cortisol levels when compared with placebo (107371). In healthy college students, clinical research also shows that taking ashwagandha root extract 350 mg twice daily for 30 days improves qualitative perceptions of stress management, but not stress scores, when compared with placebo (109589,109590). Other clinical research shows that taking ashwagandha root extract 500 mg twice daily may prevent stress-related weight gain when compared with placebo (95617).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. A small clinical study suggests that oral ashwagandha may modestly improve well-being, sleep, and alertness in elderly patients. Details: A small clinical trial in individuals aged 65-80 years shows that taking ashwagandha root extract (KSM-66, Ixoreal Biomed) 600 mg daily for 12 weeks improves overall well-being, sleep quality, and mental alertness by small to moderate amounts when compared with placebo (102684).
• Antipsychotic-induced metabolic side effects. It is unclear if ashwagandha is beneficial for attenuating the metabolic side effects of antipsychotic agents. Details: One preliminary clinical trial shows that taking a specific ashwagandha extract (Cap Strelaxin, M/s Pharmanza Herbal Pvt. Ltd.) 400 mg three times daily for one month reduces serum triglycerides by 12% and fasting blood glucose by 15% when compared with baseline levels. Patients were taking atypical antipsychotics and had modestly elevated triglycerides and fasting blood glucose levels at baseline (90649). The validity of these findings is limited by the lack of a comparator group.
• Anxiety. It is unclear if oral ashwagandha is beneficial for reducing anxiety. Details: One small clinical study shows that taking ashwagandha root (Swiss Herbals) 300 mg twice daily for 12 weeks, in combination with standard psychotherapy interventions, including dietary counseling, deep breathing exercise instruction, and a multivitamin, reduces anxiety scores when compared with standard psychotherapy interventions and placebo (19271). However, other clinical research in young adults shows that a specific ashwagandha root and leaf extract (NooGandha, Specnova LLC) 225 mg or 400 mg daily for 30 days produces similar improvements in self-reported anxiety, stress, and depression scores when compared with placebo (107370).
• Asthma. Although there has been interest in using oral ashwagandha for asthma, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Athletic performance. It is unclear if ashwagandha is beneficial for improving athletic performance. Details: A meta-analysis of four small clinical trials shows that taking ashwagandha increases aerobic capacity in athletes and non-athletes based on the measurement of maximum oxygen consumption. Effective doses ranged from 500-1000 mg daily for up to 12 weeks (102683). Another meta-analysis shows that taking ashwagandha in doses of 120-1250 mg daily, as a single dose or divided twice daily, for up to 6 months seems to improve muscle strength, speed, time to exhaustion, recovery time, and cardiorespiratory fitness in athletes and non-athletes (105824). However, the validity of this analysis is reduced by the lack of a control group, the varied training levels of the subjects, and the wide range of outcomes assessed. More research is needed to determine whether taking ashwagandha can improve athletic performance.
• Attention deficit-hyperactivity disorder (ADHD). Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In a preliminary clinical trial, children with ADHD were given a combination herbal extract formula (Nurture & Clarity), containing ashwagandha, white peony root, gotu kola, blue-green algae, bacopa, and sage, 3 mL three times daily for 4 months. Measures of attention, cognition, and impulse control improved significantly in children receiving ashwagandha when compared with placebo (19272). The dose of ashwagandha in the combination product was not reported, and the effect of ashwagandha alone in ADHD is unclear.
• Back pain. Although there has been interest in using oral or topical ashwagandha for back pain, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Bipolar disorder. It is unclear if oral ashwagandha is beneficial for improving cognitive function in adults with bipolar disorder. Details: Clinical research shows that taking ashwagandha extract (Sensoril, Natreon, Inc.) 250 mg daily for 1 week and then 250 mg twice daily for 7 weeks, improves some, but not all, measures of cognition by a small-to-moderate amount when compared with placebo (90653).
• Bronchitis. Although there has been interest in using oral ashwagandha for bronchitis, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Cerebellar ataxia. It is unclear if oral ashwagandha is beneficial for improving balance in patients with cerebellar ataxia. Details: A small, open-label study evaluating ashwagandha 500 mg three times daily in combination with Ayurvedic therapy for one month showed improvement in balance indices in subjects with cerebellar ataxia when compared with baseline (19273). The validity of this finding is limited by the lack of a comparator group. Additionally, it is unclear if this effect is due to ashwagandha, other ingredients, or the combination.
• Chemotherapy-related fatigue. Evidence is limited to one small clinical study in patients with breast cancer. Details: In preliminary clinical research in patients with breast cancer, taking ashwagandha powdered root extract 2 grams (Himalaya Drug Co) three times daily through six cycles of chemotherapy decreases chemotherapy-related fatigue when compared with no treatment. Fatigue scores were 16% to 52% higher in the control group when compared to the ashwagandha group (90651).
• Chronic obstructive pulmonary disease (COPD). It is unclear if oral ashwagandha is beneficial in patients with COPD. Details: A small clinical study in patients with stable COPD shows that taking ashwagandha root extract 250 mg twice daily for 12 weeks, along with conventional therapy, improves measures of lung function and exercise tolerance, but not quality of life, when compared with conventional therapy alone (109588).
• Cognitive function. Although there has been interest in using oral ashwagandha for cognitive function, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Constipation. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in adults with constipation shows that taking a combination product containing ashwagandha root and ambrette fruit extracts 300 mg or 500 mg daily for 14 days improves bowel movement frequency and abdominal, rectal, and stool symptoms when compared with placebo (112114). It is unclear if these effects are due to ashwagandha, ambrette, or the combination. The validity of these effects is limited by the small sample size.
• Coronavirus disease 2019 (COVID-19). Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults hospitalized with COVID-19 shows that taking a specific combination product, (Artovid-20, Bioved Pharmaceuticals) containing ashwagandha, ginger, turmeric, and Boswellia, 1,776 mg orally twice daily for 14 days shortens the duration of symptoms by 0.9 days when compared with placebo. Taking the combination product also modestly reduced the severity ratings of some symptoms, such as sore throat and cough, however, these improvements are unlikely to be clinically relevant (109899). Another small clinical study in adults with mild to moderate COVID-19 shows that taking ashwagandha 500 mg and ginger 1000 mg twice daily for 15 days reduces time to recovery by around 6 days and increases the rate of clinical cure 14-fold and 2.6-fold at days 5 and 7, respectively, when compared with a control. However, taking this combination does not appear to improve the proportion of patients with a negative COVID-19 test, viral clearance, serum antibodies, chest findings, or disease progression when compared with control (112094). The validity of these findings is limited by a lack of blinding, and the study may have been inadequately powered to detect a difference between groups. Additionally, it is unclear if these effects are due to ashwagandha, ginger, or the combination.
• Diabetes. It is unclear if oral ashwagandha is beneficial for type 2 diabetes. Details: In patients with type 2 diabetes, preliminary clinical research shows that ashwagandha 3 grams daily for 30 days decreases blood glucose to a degree similar to oral hypoglycemic drugs (19274). However, this study did not compare ashwagandha directly to a group taking oral hypoglycemic drugs.
• Fibromyalgia. Although there has been interest in using oral ashwagandha for fibromyalgia, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Hiccups. Although there has been interest in using oral ashwagandha for hiccups, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Hypercholesterolemia. It is unclear if ashwagandha is beneficial for hypercholesterolemia. Details: A very small clinical study in subjects with hypercholesterolemia shows that ashwagandha 3 grams daily for 30 days decreases serum cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) cholesterol levels when compared with baseline (19274). The validity of these findings is limited by the lack of a comparator group.
• Hypothyroidism. It is unclear if ashwagandha is beneficial for hypothyroidism. Details: Preliminary clinical research in adults with subclinical hypothyroidism shows that taking a specific ashwagandha root extract (KSM-66, Ixoreal Biomed) 300 mg twice daily for 8 weeks increases triiodothyronine (T3) and thyroxine (T4) levels by 42% and 20%, respectively, and reduces serum TSH levels by 17% from baseline. These changes are significant when compared with placebo (97292). However, the effects of ashwagandha on thyroid hormone levels in patients with overt hypothyroidism, or in patients taking prescription thyroid hormones, is unknown.
• Infertility. Although there has been interest in using oral ashwagandha for infertility in females, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Male infertility. It is unclear if oral ashwagandha is beneficial for male infertility. Details: Preliminary clinical research in males with infertility shows that taking ashwagandha root powder for approximately 3 months modestly improves hormone levels, as well as sperm count and motility, when compared with baseline (19275,90650). The validity of these findings is limited by the lack of a comparator group. One study used a specific ashwagandha root extract (KSM-66 Ashwagandha, Ixoreal Biomed) 225 mg three times daily; another study provided doses of 5 grams daily (19275,90650).
• Menopausal symptoms. Oral ashwagandha may be beneficial for menopausal symptoms. Details: A small clinical study in healthy adults in perimenopause shows that taking a specific ashwagandha root extract (KSM-66, Ixoreal Biomed) 300 mg twice daily for 8 weeks improves menopausal symptom severity by 24%, compared with 11% in those receiving placebo. Quality of life and hot flashes also were improved in those taking ashwagandha (106785).
• Obsessive-compulsive disorder (OCD). It is unclear if ashwagandha is beneficial for OCD. Details: Preliminary clinical research shows that taking ashwagandha root extract 120 mg after meals for 6 weeks, in conjunction with prescribed selective-serotonin reuptake inhibitors (SSRIs), might reduce OCD symptom severity when compared with prescribed SSRIs alone. The dose was initiated at 30 mg daily and increased by 30 mg every 4 days. Although OCD scores were significantly reduced when compared with placebo, it should be noted that scores were already significantly lower in the placebo group at baseline (95618).
• Osteoarthritis. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with osteoarthritis, taking a specific combination supplement, containing ashwagandha 450 mg, Ayurvedic zinc complex 50 mg, guggul 100 mg, and turmeric 50 mg (Articulin-F) two capsules three times daily for 3 months reduces symptoms of pain and swelling when compared with placebo. However, there were no radiological improvements (19276). It is unclear if this effect is due to ashwagandha, other ingredients, or the combination.
• Parkinson disease. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with Parkinson disease, a small clinical study shows that taking a product containing ashwagandha 14.5 grams, cowhage 4.5 grams, Hyoscyamus reticulantus 0.75 grams, and Sida cordifolia 14.5 grams in lukewarm milk twice daily for 56 days improves symptoms like tremor, stiffness, and cramps when compared with baseline. The therapy followed 28 days of cleansing or eliminative therapy using Ayurvedic remedies (6899). The validity of these findings is limited by the lack of a comparator group. Also, it is unclear if these effects are due to ashwagandha, other ingredients, or the combination. Cowhage contains levodopa, which may contribute to any benefit seen with this combination product.
• Psychological well-being. It is unclear if oral ashwagandha is beneficial for improving psychological well-being in college students. Details: A small clinical study in healthy college students shows that taking ashwagandha root extract 350 mg twice daily for 30 days improves perceptions of well-being, including improvements in energy, mental clarity, food cravings, and sleep quality, when compared with placebo. Qualitative analysis also suggests these students had improvements in stress management, but stress scores were not reduced when compared with placebo (109589,109590).
• Rheumatoid arthritis (RA). It is unclear if ashwagandha is beneficial for improving symptoms of RA. Details: Preliminary clinical research shows that taking ashwagandha powder 5 grams twice daily for 3 weeks, followed by 4 weeks of sidh makardhwaj (a mixture of gold, mercury, and sulfur) 100 mg with honey daily, modestly improves symptoms in about 50% of males and 60% of females with RA when compared with baseline (95620). The lack of a control group limits the validity of this finding. Additionally, the effect of ashwagandha powder alone is unclear.
• Sexual dysfunction. Small clinical studies suggest that oral ashwagandha root extract may help improve sexual arousal and sexual desire in some females and males with sexual dysfunction. Details: Two, small clinical studies in adult females with sexual dysfunction show that taking ashwagandha root extract (KSM-66, Ixoreal Biomed) 300 mg twice daily with food for 8 weeks in conjunction with or without counseling increases the number of successful sexual encounters and improves orgasms, satisfaction, lubrication, and arousal when compared with placebo or counseling alone (95619,110492). Also, a small clinical study in adult males with low sexual desire shows that taking the same ashwagandha root extract 300 mg twice daily after meals for 8 weeks improves subjective sexual functioning scores, including measures of sexual arousal, sexual desire, sexual behavior, and orgasm, when compared with placebo (109586).
• Smoking cessation. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing ashwagandha 100 mg, Indian gooseberry, tribulus, bacopa, Albizia lebbeck, licorice, clove, ginger, cowhage, holy basil, and turmeric (Smotect, Smotect India) daily for 3 months reduces the number of cigarettes smoked daily and levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity when compared with placebo (112115). It is unclear if these effects are due to ashwagandha, other ingredients, or the combination.
• Tuberculosis. Although there has been interest in using oral ashwagandha for tuberculosis, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Vitiligo. Although there has been interest in using oral ashwagandha for vitiligo, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Wrinkled skin. It is unclear if topical ashwagandha is beneficial in individuals with wrinkled skin. Details: A small clinical study in healthy adults with photoaged skin shows that applying ashwagandha root extract 8% lotion daily for 60 days improves physician-rated scores for skin wrinkles, hydration, brightness, tone, and pigmentation and improves other measures of skin elasticity and hydration when compared with placebo. However, changes in melanin content did not differ between treatment groups (111538).
• Wound healing. Although there has been interest in using topical ashwagandha for healing of skin ulcers and skin sores, there is insufficient reliable information about the clinical effects of ashwagandha for this condition. More evidence is needed to rate ashwagandha for these uses.

(Read more about ASHWAGANDHA)

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)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. It is unclear if topical peony is beneficial in patients with aging skin. Details: Preliminary clinical research shows that using a cosmetic ingredient containing 0.5% paeoniflorin, a constituent of peony root, for 8 weeks can reduce facial wrinkles when compared with baseline (68356). The validity of this finding is limited by the lack of a comparator group.
• Anal fissures. Although there has been interest in using topical peony for anal fissures, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Ankylosing spondylitis. Small, low-quality clinical studies suggest that oral peony, as total glucosides of peony (TGP), may improve disease symptoms in patients with ankylosing spondylitis. Details: A meta-analysis of 3 clinical trials in patients with ankylosing spondylitis (AS) shows that taking TGP 0.6 grams 3 times daily with conventional medical treatment for 12-24 weeks improves the AS disease activity score when compared with conventional treatment alone. TGP also improves inflammatory markers including erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor alpha, and interleukin-6 (112861). The reliability of these findings is limited by the low to very low quality of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Antipsychotic-induced hyperprolactinemia. Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in females with risperidone-induced hyperprolactinemia shows that taking a specific combination of peony and licorice (Peony-Glycyrrhiza Decoction; PGD) 45 grams daily for 4 weeks is similarly effective to bromocriptine for reducing prolactin levels (59775). A similar trial in males with antipsychotic-induced hyperprolactinemia shows that taking an herbal extract containing peony and licorice (shakuyaku-kanzo-to), 2.5 grams three times daily, reduces prolactin levels after 4 weeks of treatment when compared with baseline. Prolactin levels returned to baseline 4 weeks after treatment cessation (59907). The validity of this study is limited by the lack of a comparator group. Subsequently, a higher quality clinical trial in females with antipsychotic-induced hyperprolactinemia shows that taking a peony and licorice decoction (PGD) 45 grams daily for 16 weeks does not improve prolactin levels or clinical symptoms when compared with placebo (97219). However, a small clinical trial in adults with schizophrenia and sexual dysfunction due to antipsychotic-induced hyperprolactinemia shows that taking a similar PGD formulation for 8 weeks improves sexual function scores and prevents further increases in prolactin levels when compared with a non-treated control group (112412). It is unclear if any effects are due to peony, licorice, or the combination.
• Atherosclerosis. Although there has been interest in using oral peony for atherosclerosis, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral peony for CFS, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Cirrhosis. Although there has been interest in using oral peony for cirrhosis, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Cough. Although there has been interest in using oral peony for cough, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Dysmenorrhea. Although there has been interest in using oral peony for dysmenorrhea, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Dyspepsia. Although there has been interest in using oral peony for dyspepsia, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Diabetic nephropathy. It is unclear if oral peony is beneficial in patients with diabetic nephropathy. Details: Preliminary clinical research in Chinese adults with diabetic nephropathy shows that taking total glucosides of peony (TGP) 600 mg three times daily in conjunction with losartan 100 mg daily for 6 months does not improve urinary albumin excretion rate when compared with losartan alone. Taking TGP in conjunction with losartan also did not affect serum creatinine, fasting glucose, glycated hemoglobin (HbA1c), triglycerides, or total cholesterol when compared with losartan alone (98466).
• Epilepsy. It is unclear if oral peony is beneficial in patients with epilepsy. Details: Preliminary clinical research in children 1-14 years of age with intractable epilepsy shows that taking peony root extract orally 20 mg/kg twice daily for 4 weeks reduces weekly seizure frequency and average seizure duration by 80% and 83%, respectively, when compared with baseline. Approximately 63% of subjects reported a reduction in seizure frequency of at least 50% when compared with baseline. The validity of this study is limited by the lack of a comparator group (106851).
• Gout. Although there has been interest in using oral peony for gout, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Hepatitis. Although there has been interest in using oral peony for hepatitis, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Juvenile idiopathic arthritis (JIA). Small clinical studies suggest that oral peony, as total glucosides of peony (TGP), may modestly improve symptoms in patients with JIA. Details: A pooled analysis of low-quality clinical research in Chinese children 1.5-14 years of age with JIA shows that taking TGP 30-180 mg/kg daily or 600-1800 mg daily in conjunction with methotrexate for 9-26 weeks improves the odds of overall response rate by 1.5 to 2.5 times when compared with methotrexate alone. TGP also reduces erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels when compared with methotrexate alone. Preliminary subgroup analyses suggest that TGP is not effective for JIA if it is taken for 8 weeks or less (92785). Another meta-analysis of 7 small to moderate-sized clinical trials in children with JIA also shows that taking TGP 0.3 mg/kg, 30-60 mg/kg, or 1200 mg daily with conventional treatment for 12-24 weeks improves effectiveness rates when compared with conventional treatment alone. TGP also reduces ESR, CRP, and tumor necrosis factor alpha (TNF-α) (112861). The reliability of these findings is limited by the variability in the quality of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Mastalgia. Although there has been interest in using oral peony for mastalgia, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Migraine headache. Although there has been interest in using oral peony for migraine, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Muscle cramps. Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary, low-quality, clinical research shows that taking a specific combination of peony and licorice (shakuyaku-kanzo-to) orally, 2.5-6 grams daily for up to 4 weeks, relieves muscle cramps when compared to baseline in patients undergoing hemodialysis (13551,13552). The validity of these studies is limited by the lack of a comparator group. It is also unclear if this effect is due to peony, licorice, or the combination.
• Neuropathic pain. Although there has been interest in using oral peony for neuropathic pain, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Osteoarthritis. Some low-quality clinical studies suggest that oral peony, as total glucosides of peony (TGP), may modestly improve symptoms in patients with osteoarthritis. Details: A meta-analysis of 4 moderate-sized clinical trials in adults with osteoarthritis shows that taking TGP 0.6 grams 2 or 3 times daily with conventional medical treatment for 4-12 weeks improves joint pain when compared with conventional treatment alone (112861). The reliability of these findings is limited by the low quality and high heterogeneity of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Pancreatitis. It is unclear if rectal peony is beneficial in patients with pancreatitis. Details: Preliminary clinical research in adults with moderate to severe acute pancreatitis shows that rectal administration of 150 mL water containing 15 grams of red peony root granules twice daily for 7 days in addition to standard care reduces the time to resolution of abdominal pain and normal bowel habits by 25% when compared with a placebo enema. Additionally, patients receiving red peony root had an average 2-day reduction in hospital stay and a greater improvement on the modified Balthazar CT score when compared with placebo (104283).
• Polycystic ovary syndrome (PCOS). Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking peony root extract 2250 mg daily, along with Ceylon cinnamon, levant berry, St. John's wort, Tribulus, and licorice, during the follicular phase of the menstrual cycle for 3 months reduces the rate of oligomenorrhea or amenorrhea by 33% and the time between menstrual cycles by 43 days when compared with lifestyle modification alone. Taking this combination also improves quality of life by about 30% and modestly reduces body weight and body mass index when compared with lifestyle intervention alone. Although taking this combination improved conception rate by 4-fold, live birth rate was similar to lifestyle intervention alone (97216). It is unclear if these effects are due to peony, the other ingredients, or the combination.
• Premenstrual syndrome (PMS). Although there has been interest in using oral peony for PMS, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Psoriasis. It is unclear if oral peony is beneficial for plaque psoriasis. Details: Preliminary clinical research in Chinese adults with moderate to severe plaque psoriasis shows that taking total glucosides of peony (TGP) 600 mg three times daily in conjunction with acitretin for 12 weeks does not improve plaque size or severity when compared with acitretin alone. However, taking TGP in combination with acitretin might increase the number of patients achieving a 50% reduction in plaque size when compared with acitretin alone (97950).
• Psoriatic arthritis. Small, low-quality clinical studies suggest that oral peony, as total glucosides of peony (TGP), may improve symptoms in patients with psoriatic arthritis. Details: A meta-analysis of 2 small clinical trials in adults with psoriatic arthritis shows that taking TGP 0.6 grams 3 times daily with conventional medical treatment for 12-24 weeks improves Psoriasis Area and Severity Index (PASI) scores and the inflammatory marker erythrocyte sedimentation rate when compared with conventional treatment alone (112861). The reliability of these findings is limited by the low quality and high heterogeneity of the included studies. Additionally, all of the studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Respiratory tract infections. Although there has been interest in using oral peony for respiratory tract infections, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Restless legs syndrome (RLS). Oral peony has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 12 low-quality clinical studies in Chinese patients with RLS shows that taking peony-containing combination herbal preparations along with conventional therapy appears to improve sleep quality and decrease RLS symptoms when compared with conventional therapy alone. A few of the studies included in this analysis also suggest that taking peony-containing herbal products alone might be more effective than conventional therapy for RLS (100991). The peony-containing products included in this analysis contained between 4-15 other herbal ingredients. It is unclear whether the effects are due to peony, other ingredients, or the combination.
• Rheumatoid arthritis (RA). It is unclear if oral peony is beneficial in patients with RA; evidence is conflicting. Details: Although low-quality clinical research in patients with RA has shown that use of total glucosides of peony (TGP) in conjunction with standard treatment for 4-24 weeks reduces inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein when compared with standard treatment alone, effects on RA symptoms are conflicting (92786,101245,112861). A pooled analysis of clinical research in adults with RA shows that taking TGP in conjunction with leflunomide for 4-24 weeks is less effective for reducing RA symptom scores than taking leflunomide alone (92786). In contrast, another pooled analysis of clinical research in adults with RA shows that taking TGP for 12-24 weeks in combination with methotrexate improves swollen joint count, but not other symptoms such as morning stiffness and tender joint count, when compared with methotrexate alone. Preliminary subgroup analyses also suggest that taking TGP in conjunction with methotrexate might reduce overall adverse effects when compared with methotrexate alone (101245). Of note, the dose of TGP used is not reported in most trials included in these two analyses. Another meta-analysis of 10 mostly small to moderate-sized clinical trials in adults with RA shows that taking TGP 0.6 grams 1-3 times daily with conventional medical treatment for 12-48 weeks improves symptoms as evaluated with the Disease Activity of 28 joints (DAS28) scale when compared with conventional treatment alone (112861). However, these analyses are all limited by the low quality of the included studies. Additionally, all of the included studies were conducted in China; it is unclear if findings can be applied to other geographical regions and populations.
• Sjogren syndrome. It is unclear if oral peony is beneficial in patients with Sjogren syndrome. Details: Some clinical research in Chinese adults with Sjogren syndrome shows that taking total glucosides of peony (TGP) 600 mg three times daily for 24 weeks improves overall symptoms, with the greatest effects on symptoms of dry eye and fatigue, when compared with placebo (100992). An earlier and smaller clinical study from the same research group found that taking TGP at the same dose and duration improved symptoms of dry mouth, but did not reduce overall symptom scores or other markers of disease, when compared with placebo (97949). However, this study was not adequately powered to detect differences in overall symptom scores between TGP and placebo.
• Spasticity. Although there has been interest in using oral peony for spasticity, there is insufficient reliable information about the clinical effects of peony for this purpose.
• Systemic lupus erythematosus (SLE). Small clinical studies suggest that oral peony, as total glucosides of peony (TGP), may modestly improve disease activity scores in patients with SLE. Details: A meta-analysis of 13 small to moderate-sized, low-quality clinical studies in patients with SLE shows that taking TGP 0.6 grams 2-3 times daily or 1.2 grams twice daily for 1-6 months in conjunction with conventional treatment modestly improves the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score when compared with conventional treatment alone. Analyses of secondary endpoints which were not available for all studies show that TGP also improves markers of SLE disease activity, including erythrocyte sedimentation rate (ESR) and C-reactive protein, reduces the average daily dose of glucocorticoids and the cumulative dose of cyclophosphamide, and decreases the rate of disease recurrence (110432). However, the validity of the findings from this meta-analysis is limited by the heterogeneity of the included studies, which enrolled patients of varying age and disease severity. Additionally, a similar meta-analysis of 8 small to moderate-sized, low-quality clinical studies in adults with SLE shows that taking TGP 0.6 grams 2-3 times daily for 3-12 months in conjunction with conventional treatment of glucocorticoids and/or immunosuppressants improves SLEDAI scores when compared with conventional treatment alone. TGP also improves markers of inflammation such as ESR, levels of immunoglobulins A, G and M, and complement 3 and 4 (112862). The validity of these finding is also limited by substantial heterogeneity which may be due to differences in conventional therapies. In addition, all of the studies included in these meta-analyses were conducted in China; it is unclear if findings can be applied to other geographical regions and populations. More evidence is needed to rate peony for these uses.

(Read more about PEONY)

POSSIBLY EFFECTIVE

• Cognitive function. Oral sage seems to be beneficial for improving cognitive function in healthy adults. The benefits of sage aromatherapy are unclear. Details: Clinical research shows that taking a specific product providing common sage polyphenols and Spanish sage terpenoids (Cognivia), either as a single dose or daily for 29 days, modestly improves working memory and accuracy when compared with placebo. A single dose of this product contains common sage leaf extract 400 mg and Spanish sage essential oil 200 mg (105337). In addition, preliminary clinical research shows that Spanish sage essential oil 25-50 mcL orally as a single dose seems to dose-dependently enhance some measures of cognitive performance in young adults by a small amount (10811,72609,72616,72660). When used as aromatherapy, essential oils of common sage, but not Spanish sage, seem to improve quality of memory and secondary memory. Neither species improves speed of memory or working memory when used as aromatherapy. In this study, five drops of common sage essential oil and 5 mL water were placed on a warmed stone and allowed to diffuse for 5 minutes prior to exposure (72658).
• Hyperlipidemia. Oral sage seems to be beneficial for reducing low-density lipoprotein (LDL) cholesterol and triglyceride levels. Details: Clinical research in adults with mixed hyperlipidemia types shows that taking common sage leaf extract 500 mg, standardized to quercetin 2.16%, three times daily for 2 months reduces LDL cholesterol and triglyceride levels by about 20% and 23%, respectively, and increases high-density lipoprotein (HDL) cholesterol levels by 20%, when compared with placebo (72662). Also, preliminary clinical research in adults with type 2 diabetes and hypercholesterolemia shows that taking common sage leaf extract 500 mg three times daily for 3 months lowers total cholesterol by 17%, LDL cholesterol by 36%, and triglycerides by 56%, and increases HDL cholesterol by 28%, when compared with placebo (91971).
• Menopausal symptoms. Oral sage seems to be beneficial for reducing menopausal symptoms. Details: Clinical research shows that taking a thujone-free common sage extract (Menosan, A.Vogel AG) 280 mg daily for 4 weeks reduces overall symptoms of menopause by 39% when compared with placebo. About 41% of patients taking common sage had at least a 50% reduction in symptoms, compared with 8% of those taking placebo. Hot flushes, sleep problems, joint and muscle discomfort, irritability, and physical and mental exhaustion were improved, whereas urogenital symptoms such as sexual desire and vaginal dryness were not (105338). Other clinical research shows that taking common sage extract 300 mg daily for 3 months moderately reduces overall symptoms of menopause after about 10 weeks when compared with placebo. However, there was no effect on vaginal dryness, physical and mental exhaustion, or urinary incontinence (103379). Another small clinical study shows that taking a specific thujone-free common sage extract (Sage Menopause, Bioforce AG) 280 mg daily for 56 days reduces daily hot flash frequency by 40% and reduces hot flash intensity when compared with baseline (17177). The validity of these findings is limited by the lack of a comparator group.

POSSIBLY INEFFECTIVE

• Postoperative pain. Using an oral rinse containing common sage does not seem to be beneficial for reducing postoperative pain. Details: A large open-label clinical trial in children and adults shows that using a common sage oral rinse 6 times daily in combination with ibuprofen or diclofenac is less effective than benzydamine hydrochloride, a local anesthetic, for reducing pain following tonsillectomy and/or adenoidectomy. Furthermore, treatment with common sage oral rinse is associated with an increased risk of postoperative infection in adults when compared with benzydamine hydrochloride (72700).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if a single oral dose of common sage is beneficial for age-related cognitive decline. Details: Clinical research in healthy, older adults shows that taking a single dose of common sage extract 333 mg improves accuracy of attention and some measures of memory when compared with placebo. However, not all doses were effective and some measures of cognitive function were not affected (72642).
• Alzheimer disease. It is unclear if oral sage is beneficial for Alzheimer disease. Details: Preliminary clinical research shows that taking extracts of common sage and Spanish sage orally seems to improve cognitive function in patients with mild to moderate Alzheimer disease when used for up to 4 months (10334,10810). In one study, a fixed dose of common sage hydroalcoholic extract, equivalent to 1 gram of sage per day, was used for 4 months (10810). In the other, an extract of Spanish sage titrated up to 2.5 mg three times daily for 6 weeks was used (10334). These studies are limited by their short duration and small numbers of participants.
• Androgen deprivation therapy (ADT)-associated hot flashes. It is unclear if oral sage is beneficial for ADT-associated hot flashes. Details: Preliminary clinical research in patients with prostate cancer receiving ADT shows that taking common sage extract 150 mg three times daily with meals for 4 weeks reduces hot flash severity by 48% and hot flash frequency by 42% when compared with baseline. These improvements were maintained with an additional 8 weeks of treatment (91970). The validity of these findings is limited by the lack of a comparator group.
• Athletic performance. It is unclear if oral sage is beneficial for improving athletic performance. Details: In young, healthy, physically active adults, taking a specific supplement (Cognivia, Nexira) containing 400 mg common sage leaf extract and 200 mg Spanish sage oil, orally 2 hours prior to a 40-minute stationary cycling session at 80% of maximum aerobic power, lowers perceived exertion scores and improves working memory and reaction times when compared with placebo (108961).
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if topical sage is beneficial for the treatment or prevention of CINV. Details: A small clinical study in patients undergoing chemotherapy shows that using common sage oil 2 mL topically during 15-minute sessions of Swedish abdominal massage twice daily for 3 days modestly reduces nausea severity scores, but does not affect vomiting frequency, when compared with massage alone (107023).
• Dental plaque. It is unclear if rinsing the mouth with sage is beneficial for reducing plaque. Details: Preliminary clinical research shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), is as effective as normal saline for reducing dental plaque. However, there was no effect on tongue plaque. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Diabetes. It is unclear if oral sage is beneficial for diabetes. Details: A small clinical study in adults with type 2 diabetes shows that taking common sage leaf extract 500 mg three times daily for 3 months lowers fasting blood glucose by 32% and glycated hemoglobin (HbA1c) by 23% when compared with placebo (91971). However, another small clinical study in patients with type 2 diabetes shows that taking common sage extract 150 mg three times daily for 3 months does not lower fasting blood glucose or HbA1c when compared with placebo, although there is a modest reduction in 2-hour postprandial blood glucose levels (105340). A meta-analysis of 3 small studies, including the 2 described above, shows that taking common sage, 150-500 mg three times daily for 2-3 months, modestly reduces fasting blood glucose and 2-hour postprandial blood glucose levels, as well as HbA1c, when compared with placebo (108962). These studies were all conducted in Iran; it is unclear if these findings are generalizable to other geographic locations.
• Dry mouth. It is unclear if rinsing the mouth with common sage is beneficial for dry mouth. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in conjunction with standard care involving brushing and an oral gel (Biotene), is as effective as normal saline for improving overall oral health and modestly more effective than normal saline for improving dry mouth. The rinse was made by steeping 2.5 grams dried sage leaf in 100 mL boiled water for two minutes (105339).
• Gingivitis. Sage has only been evaluated as a mouthwash in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in elderly individuals shows that rinsing the mouth with a mouthwash containing sage, marshmallow, calendula, tormentil, horse chestnut, neem, and myrrh, once daily for 30 seconds for 6 weeks, is no more effective than placebo for improving plaque and gingival bleeding (105341).
• Herpes labialis (cold sores). It is unclear if topical sage is beneficial for herpes labialis. Details: Clinical research shows that topical application of a cream containing either sage alone or sage with rhubarb, starting within 1 day of the first symptoms and continuing for 10-14 days, heals herpes labialis legions in 7.6 days or 6.7 days, respectively, compared to a healing time of 6.3 days with acyclovir cream. The combination of sage and rhubarb also improves the time to healing and reduces pain when compared with sage alone. The cream provided 23 mg sage extract, with or without 23 mg rhubarb extract, per gram and was applied every 2-4 hours while awake (10437).
• Lung cancer. It is unclear if dietary sage is beneficial for lung cancer prevention. Details: Epidemiological research has found that regularly consuming sage is associated with a 54% lower risk of developing lung cancer when compared with those who do not use sage as a spice (72593).
• Oral mucositis. It is unclear if rinsing the mouth with sage is beneficial for oral mucositis. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a rinse containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), does not improve oral mucositis when compared with baseline or normal saline rinse. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Pharyngitis. It is unclear if inhaling a spray containing sage, with or without other ingredients, is beneficial for pharyngitis. Details: Clinical research in patients with acute viral pharyngitis shows that inhaling three puffs (140 mcL) of a specific spray (Valverde Salvia Rachenspray) containing common sage extract 15%, six to nine times daily for 3 days, reduces throat pain intensity over 2 hours when compared with placebo. However, sprays containing common sage extract 5% or 30% do not seem to be more effective than placebo for reducing throat pain (72619). Other preliminary clinical research in patients with sore throat due to acute pharyngitis or tonsillitis shows that applying a combination spray product containing common sage leaf tincture 430 mg/mL, Echinacea flowering aerial parts tincture 863.3 mg/mL, and Echinacea root tincture 45.5 mg/mL, every 2 hours up to 10 times daily for up to 5 consecutive days improves symptoms as effectively as a chlorhexidine-lidocaine spray (20077).
• Polycystic ovary syndrome (PCOS). It is unclear if oral sage is beneficial for PCOS. Details: Clinical research shows that taking common sage extract 330 mg daily for 8 weeks modestly reduces body mass index (BMI), diastolic blood pressure, and fasting blood glucose, and modestly improves measures of insulin resistance, when compared with placebo in individuals with PCOS. However, there was no effect on waist to hip ratio or systolic blood pressure (103380).
• Sunburn. It is unclear if topical sage is beneficial for sunburn prevention. Details: Clinical research shows that a single application of a hydrophilic ointment containing common sage extract 2% to the skin immediately after exposure to ultraviolet light reduces the development of skin redness when compared with placebo (72638).
• Swallowing dysfunction. It is unclear if rinsing the mouth with sage is beneficial for swallowing dysfunction. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), does not improve swallowing when compared with baseline or normal saline rinse. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Tonsillitis. Sage has only been evaluated in a spray in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with sore throat due to acute pharyngitis or tonsillitis shows that applying a combination spray product containing common sage leaf tincture 430 mg/mL, Echinacea flowering aerial parts tincture 863.3 mg/mL, and Echinacea root tincture 45.5 mg/mL, every 2 hours up to 10 times daily for up to 5 consecutive days improves symptoms as effectively as a chlorhexidine-lidocaine spray (20077).
• Tonsillopharyngitis. It is unclear if oral sage is beneficial for treating tonsillopharyngitis. Details: A moderate-sized observational study in patients aged 12-75 years old with acute tonsillopharyngitis suggests that taking lozenges containing sage extract 378.5 mg and echinacea extract 5 times daily for 4 days reduces throat pain and tonsillopharyngitis symptoms when compared to baseline, both acutely within 90 minutes and after 4 days of treatment (111530). The validity of these findings is limited by the lack of a comparator group. Also, it is unclear if these effects are due to sage, echinacea, the combination, or natural resolution of the condition. More evidence is needed to rate sage for these uses.

(Read more about SAGE)

POSSIBLY EFFECTIVE

• Breast cancer. High dietary intake of soy might be beneficial for the prevention of breast cancer and breast cancer recurrence in some patients. However, soy supplements do not seem to be beneficial. Details: For prevention, most population research has found that higher dietary intake of soy is associated with up to a 26% reduced odds of developing breast cancer when compared with a lower intake (7335,7336,11038,11807,75377,75587,90955,108251). One meta-analysis of population research found that patients who consumed more than 15 mg soy isoflavones daily made up about 25% of all cases of breast cancer, compared with 75% of cases in the group of patients consuming less than 15 mg daily (108251). The effects appear to vary depending on the ethnicity of the patient. Population research has consistently found that a high-soy diet in Asian and Asian-American females is associated with a significantly reduced risk of breast cancer (7335,7336,11038,11807,75377,75587,90955). However, the amount of soy consumed in a Western diet, even among those who consume the highest amounts of soy, was not found to have a preventative effect (11391,17109,90955,90967). The reason for the disparate findings are unknown but may be related to genetic differences or differences in quantification of soy intake (7663,94153). Also, the prophylactic benefit seems to apply regardless of whether high amounts of soy are consumed during adolescence or later in life (7335,7336,9674). Limited population research has also found that consuming a diet high in soy is associated with up to a 25% reduced risk of breast cancer recurrence; however, it is unclear whether there is an association with reduced mortality in breast cancer patients (90956,90969,94154). The effect appears to be greater for certain subgroups of breast cancer patients. Increased dietary soy intake is associated with a 28% to 36% risk reduction in patients with estrogen receptor (ER)-negative tumors, a 30% risk reduction in patients with ER-positive/progesterone receptor (PR)-positive tumors, and a 25% to 36% risk reduction in postmenopausal patients (90956). Some small clinical studies have also evaluated the use of soy isoflavone extract . One small clinical study in patients with breast cancer shows that taking a soy isoflavone extract 200 mg daily for 2 weeks prior to surgery does not seem to affect cancer cell growth when compared with a historical control (11042). Another small clinical study in patients at high risk for breast cancer or with a history of breast cancer shows that taking a soy tablet containing 50 mg soy isoflavones (Novasoy, Archer Daniels Midland Co.) daily for 12 months does not alter mammographic or breast tissue density when compared with placebo (95999).
• Chronic kidney disease (CKD). Oral soy protein seems to improve some measures of disease severity in patients with CKD. Details: Clinical research shows that consuming soy protein seems to reduce proteinuria in people with kidney disease (2286,2287,2288,75249,75634). Also, a meta-analysis of clinical research in patients with CKD who are not on dialysis shows that soy protein intake reduces serum levels of creatinine by 0.07 mg/dL, phosphorus by 2.5 mg/dL, and triglyceride by 18 mg/dL when compared with placebo or control (90989).
• Diabetes. Diets high in soy seem to reduce the risk of type 2 diabetes. Also, oral soy protein, but not soy isoflavones, seems to modestly improve glycemic indices. It is unclear if soy is beneficial for lowering blood lipid levels or reducing cardiovascular (CVD) mortality risk in adults with type 2 diabetes. Details: A meta-analysis of observational studies has found that higher dietary intake of tofu, soy protein, or soy isoflavones is associated with an 8% to 16% lower risk of developing diabetes when compared with a lower dietary intake (105608). In menopausal patients without diabetes, a meta-analysis of clinical research shows that intake of soy isoflavones 40-161 mg daily seems to improve glycemic indices when compared with control (96423). Some research shows that soy can modestly improve glycemic indices in patients with diabetes. A meta-analysis of small low-quality clinical studies in patients with diabetes or metabolic syndrome shows that taking various formulations of soy protein modestly reduces fasting plasma glucose and insulin levels, as well as insulin resistance, when compared with control (96001). An older meta-analysis assessing both healthy patients and patients with diabetes shows that a whole soy diet reduces fasting blood glucose by about 4 mg/dL when compared with control (75493). Small clinical studies also suggest that an extract of the fermented soybean product, Touchi, acts as an alpha-glucosidase inhibitor. It seems to modestly lower blood glucose, glycated hemoglobin (HbA1c), and triglycerides in patients with type 2 diabetes (11762,75205). However, some conflicting evidence exists. A meta-analysis of small, low-quality clinical studies in patients with type 2 diabetes shows that taking soy isoflavones does not improve glycemic indices when compared with control (105610). Also, another meta-analysis of clinical research in patients with type 2 diabetes shows that taking soy protein and/or soy isoflavones for 6-12 weeks does not improve glycemic indices when compared with either soy protein without isoflavones, other protein, or placebo (105610). Reasons for these conflicting results are unclear but may relate to differences in baseline blood glucose levels, the formulation of soy, or the duration of treatment. Some research shows that soy may modestly improve the lipid profile in patients with diabetes. A meta-analysis of clinical research in patients with diabetes shows that taking soy protein and/or soy isoflavones for 6-12 weeks modestly reduces levels of total and low-density lipoprotein (LDL) cholesterol, but not high-density lipoprotein (HDL) cholesterol or triglycerides, when compared with control (105610). Consuming soy foods might reduce the risk of mortality related to CVD in patients with diabetes. Population research suggests that consuming soy foods at least four days each week is associated with a 23% reduced risk of CVD mortality when compared with never consuming soy foods. Consuming soy foods less than four times weekly is not associated with CVD mortality risk (108242). Soy is also of interest in the prevention or treatment of gestational diabetes. Population research has found that consumption of less than 40 grams of soy daily in the second trimester is associated with a 2.1-fold increased risk of gestational diabetes when compared with daily soy intake of 40 grams or more (108241). Also, a small clinical trial in patients with gestational diabetes shows that consuming a diet containing about 0.3 grams/kg soy protein for 6 weeks, beginning at 24-28 weeks' gestation, reduces blood glucose levels, insulin resistance, and triglyceride levels when compared with consuming a non-soy control diet (95993).
• Diarrhea. Oral soy fiber seems to reduce acute diarrhea in infants, although it may not be beneficial in adults. Details: Giving soy fiber-supplemented formula orally, either alone or in combination with oral rehydration solution, seems to reduce the duration of acute diarrhea in infants when compared with cow's milk formula or oral rehydration solution alone (2291,2292,75474,75517,75523,75531,75572). However, in some studies, a reduction in the duration of acute diarrhea was not observed when compared with cow's milk formula (75522,75542). In adult patients receiving nutrition via intubation, preliminary clinical research suggests that treatment with soy-polysaccharide fiber does not improve the incidence of diarrhea when compared to control (75508).
• Galactosemia. Oral soy protein can be used in infant formula to prevent symptoms of galactosemia. Details: Soy does not contain the sugar galactose. Some research suggests that giving oral isolated soy protein-based formula in place of milk-based formula to infants seems to be helpful for preventing symptoms of galactosemia (3400).
• Hyperlipidemia. Oral soy protein seems to modestly reduce lipid levels. However, purified soy isoflavone may not have the same benefit. Details: Consuming soy protein orally, in place of other dietary protein, seems to modestly reduce total cholesterol and low-density lipoprotein (LDL) cholesterol by about 3% to 4% when compared with control (842,2293,2294,2296,2585,3402,4755,6412,7346,7803)(8530,10459,42059,75356,105598,105604). Additionally, some research shows that soy protein might be more effective in patients with more severe hyperlipidemia (75497). The FDA has approved labeling for specific soy products that states that they may be used for cholesterol reduction in combination with a diet low in saturated fat and cholesterol. To be eligible for this labeling, soy products must provide at least 6.25 grams of soy protein per serving, which is 25% of the effective daily intake (3977). However, not all evidence is positive. Some studies have shown no benefit of soy protein or isoflavones on LDL cholesterol levels when compared to control (8521,9679,12034,17105,53771,75236)(75242,75274,75276). Furthermore, although a few clinical trials have shown significant decreases in triglycerides following supplementation with soy or soy protein isolate (75258,75365), most studies suggest that soy protein does not decrease triglycerides when compared to control (2293,6412,8530,12034,17105). The effect of soy protein on high-density lipoprotein (HDL) cholesterol is inconsistent. Most studies suggest that it does not increase HDL levels (2293,6412,8530,12034,75286)(75524), although some analyses of clinical research suggest that soy might increase HDL cholesterol levels by up to 4% when compared to control (75480,75497). Doses of soy protein have ranged from 25-135 grams daily, providing 40-318 mg daily of isoflavones; however, higher doses do not seem to be more effective (17106,105598). Some evidence suggests that soy protein providing more isoflavones, or supplemented with isoflavones, might be more effective (3402,6413,10459), but this has not been consistently found in studies (3402). Most studies evaluating soy protein products containing little to no isoflavones suggest that these products are not effective (3402,7346,9679); however, purified soy isoflavone supplements alone do not seem to decrease LDL cholesterol (851,4738,7345,8502,10459,14066). In addition to soy protein, limited evidence suggests that soy fiber alone might reduce total cholesterol, LDL cholesterol, and triglyceride levels when compared with placebo (75686,75689). There is also some evidence that ultra-high temperature (UHT) treatment of soy milk destroys any cholesterol-lowering activity (17106).
• Hypertension. Oral soy seems to modestly reduce blood pressure in some patients. Details: A meta-analysis of the available clinical research shows that consuming soy products modestly lowers systolic and diastolic blood pressure by an average of 1.6 mmHg and 1.2 mmHg, respectively, when compared with control (105605). This analysis is limited by high risk of bias and the lack of a dose-response relationship. An older meta-analysis, as well as individual clinical studies, in patients with prehypertension or mild hypertension show that consuming soy protein 18-40 grams, providing 118-143 mg of isoflavones, daily or black soy peptide 4.5 grams daily for 8 weeks reduces systolic blood pressure by about 4-8 mmHg and diastolic blood pressure by about 3-5 mmHg when compared with control (1313990962,90965). In normotensive patients, soy protein does not seem to reduce systolic or diastolic blood pressure (90965).
• Lactose intolerance. Oral soy protein can be used in infant formula to prevent symptoms of lactose intolerance. Details: Providing isolated soy protein-based formula orally to infants is an acceptable alternative to milk-based formulas, especially for infants with symptoms of lactose intolerance (3400).
• Menopausal symptoms. Oral soy seems to reduce hot flashes in patients with menopausal symptoms. Details: Consuming soy protein 15-60 grams, providing 34-100 mg of isoflavones, daily seems to modestly decrease the frequency and severity of hot flashes in some menopausal adults. Improvement seems to be greater in those with a higher frequency of hot flashes at baseline (2296,2297,3978,3986,3987,7653,9917,11805,15220,17110,75478)(75486,75649,92661,95997). Taking concentrated soy isoflavone extracts, providing 35-200 mg of isoflavones, daily seems to have similar effects (4751,6455,7802,9916,10460,11805,11993,11994,13209,15220)(15850,75478,90950,90979,92661). Higher doses of 100-200 mg of isoflavones daily and higher frequency of dosing intervals seem to have greater benefit (90950). Furthermore, the amount of the specific isoflavone genistein contained in a soy product may influence outcomes. According to one analysis, studies using products that provide at least 15 mg of genistein daily consistently show positive outcomes. Studies using products containing a lower concentration of genistein have produced inconsistent findings (15133). Not all research has found that soy extracts reduce hot flashes (7801,11806,14062,15038,15851,16762); some experts speculate that this is due to a high placebo response (9916). Some clinical research has compared soy isoflavone extracts to conventional estrogen replacement. In one study, a concentrated soy isoflavone extract of genistein 54 mg daily reduced hot flashes by 22% to 29%, compared to 54% in those taking 17beta-estradiol as 1 mg daily plus norethisterone acetate 0.5 mg daily (11994). Additional preliminary research suggests that taking a soy isoflavone extract providing 60 mg isoflavones twice daily is comparable in efficacy to conjugated estrogens 0.625 daily for reducing menopausal symptoms. Conjugated estrogens seem to work more quickly; it seems to take up to 2 months to achieve the full effect of soy isoflavones (13209). One clinical trial compared soy isoflavones 10-40 mg daily to S-equol, a soy isoflavone metabolite. Soy isoflavones were less effective for reducing hot flash frequency when compared with S-equol (90960). This has led to some speculation that the effectiveness of soy in relieving hot flashes is influenced by a patient's ability to convert daidzen, a soy isoflavone, to S-equol (90950). It is theorized that patients who are S-equol producers are more likely to achieve symptom relief from soy. However, observational and clinical research does not support this theory (90990,94162). Soy has also been evaluated for the management of other symptoms of menopause. Some clinical research in menopausal patients with depression suggests that taking soy 100 mg, providing 50 mg of soy isoflavones, in combination with sertraline 50 mg daily for three months improves depression severity when compared with sertraline or soy alone (90958). An analysis of two small clinical trials shows that supplemental soy providing 50-118 mg of isoflavones can reduce vaginal dryness scores by 0.26 when compared with control (92661). Also, an open-label study suggests that drinking a specific beverage (ViveSoy) containing soy protein 15 grams and soy isoflavones 50 mg orally daily for 12 weeks reduces overall urogenital symptoms when compared with a control group (95997). However, one small clinical study in perimenopausal patients shows that a soy-rich diet does not relieve urogenital symptoms, including vaginal dryness, itching, and urinary incontinence, when compared with a soy-free diet (75285).
• Metabolic syndrome. Oral soy protein seems to improve glycemic control and other markers of metabolic syndrome. Details: A meta-analysis of clinical research in patients with diabetes or metabolic syndrome shows that following a diet high in soy protein can decrease fasting plasma glucose and insulin levels, as well as insulin resistance, when compared with a control diet. Furthermore, dietary intake of soy protein modestly decreases diastolic blood pressure and low-density lipoprotein (LDL) cholesterol by a small amount in this population, although there is no effect on systolic blood pressure, high-density lipoprotein (HDL) cholesterol, or triglycerides (96001). Other clinical research shows that consuming a soy nut diet or a soy protein diet reduces fasting plasma glucose and LDL cholesterol levels when compared to baseline in postmenopausal adults with metabolic syndrome; however, the soy nut diet seems to more beneficial than either the soy protein diet or a Dietary Approaches to Stop Hypertension (DASH) diet (75378).
• Muscle strength. Oral soy protein seems to increase muscle strength. Details: Overall, soy protein combined with resistance training seems to increase muscle strength when compared with placebo (16748,75246,96942,98871). A meta-analysis of three clinical studies shows that consuming soy protein in addition to resistance training improves strength and lean body mass in untrained athletes (98871). Other clinical research shows that soy also improves muscle strength in trained athletes and postmenopausal adults (75246,96942). One study in Olympic endurance athletes shows that consuming isolated soy protein (Supro) 1.5 grams/kg daily for 8 weeks increases body mass and strength indices and reduces fatigue when compared with no protein supplementation (75246). Clinical research in postmenopausal adults undergoing resistance training 3 days weekly shows that taking soy protein 25 grams daily in skim milk for 16 weeks increases the maximum amount of weight lifted in one repetition by over 80% for both bench press and knee extension when compared to a maltodextrin placebo (96942). Soy protein has also been compared with other protein supplements. A meta-analysis of preliminary clinical studies and other clinical research show that soy protein seems to work as well as whey, beef, and dairy (casein and whey) protein for improving muscle strength (75404,85941,98871,105591). However, the validity of these findings is limited by the small size and high heterogeneity of the studies.
• Osteoporosis. Oral soy isoflavones seem to improve bone density and reduce the risk of osteoporosis in post-menopausal adults. Details: Most clinical research suggests that soy protein or soy extract containing 75-90 mg of isoflavones can increase bone mineral density (BMD), or slow BMD loss, and improve biochemical markers of bone turnover in peri- and postmenopausal adults when compared with control (842,4951,6449,9775,11082,90972,90980). Lower doses of isoflavones do not seem to be as beneficial. However, some observational research in postmenopausal Japanese adults and Chinese females aged 30-40 years has found that consuming about 50 mg dietary soy isoflavones daily is associated with a higher BMD when compared with lower soy isoflavone intake (7342,11081). An observational study in postmenopausal Asian patients has found that consuming higher dietary soy protein is associated with a lower risk of developing fractures when compared with lower amounts (13181). However, not all research has been positive. Some conflicting evidence suggests that soy protein does not improve BMD in some postmenopausal adults. The discrepancy in findings may be due to differences in soy formulations, concomitant treatments, or variable patient populations (4952,12034,14064,90978). For example, most evidence shows that soy does not affect BMD in premenopausal patients or bone turnover in adolescents (7660,8532,9684,11086). It is theorized that only people who can convert daidzein, a soy isoflavone, to S-equol might obtain benefits from soy (4952). However, clinical research suggests that there is no difference in bone calcium retention between equol producers and nonproducers (95995).

POSSIBLY INEFFECTIVE

• Benign prostatic hyperplasia (BPH). Oral soy does not seem to reduce BPH symptoms. Details: Clinical research in patients with BPH shows that taking soy isoflavones 40 mg (Soylife 40, Acatris) daily for 12 months does not improve peak urine flow rate, residual urine volume, symptoms of BPH, or general quality of life when compared with placebo (90983).
• Breast cancer-related hot flashes. Oral soy does not seem to reduce the risk for breast cancer-related hot flashes. Details: Clinical research shows that consuming a soy beverage providing soy isoflavones 90 mg daily or taking a soy extract providing soy isoflavones 50 mg three times daily does not reduce hot flashes in breast cancer survivors (3991,7658,8499). Observational research in breast cancer survivors has also found no association between hot flash incidence and soy isoflavone consumption (105602).
• Colorectal cancer. Oral soy does not seem to reduce the risk for colorectal cancer. Details: Some observational research from China and Japan has found that intake of soy protein or soy isoflavone is not associated with the risk of developing colorectal cancer (105601). Furthermore, some clinical research shows that soy protein powder 58 grams containing isoflavones 83 mg, taken daily for 12 months, does not reduce the proliferation of colorectal epithelial cells in patients with adenomatous polyps when compared to control (75282).
• Exercise-induced muscle soreness. Oral soy does not seem to reduce muscle soreness after exercise. Details: Some clinical research shows that taking soy isoflavone extract 120 mg orally for 30 days prior to exercise doesn't ameliorate muscle soreness caused by exercise when compared with placebo (8524).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if oral soy improves cognition in patients with Alzheimer disease. Details: Preliminary clinical research in patients with Alzheimer disease shows that taking soy isoflavones (Novasoy, Archer Daniels Midland Co.) 100 mg daily for 6 months does not improve cognition when compared with placebo (96424).
• Androgen deprivation therapy (ADT)-associated hot flashes. One small clinical study in patients with prostate cancer receiving ADT shows that taking soy protein powder 20 grams, providing 160 mg of isoflavones, alone or along with venlafaxine 75 mg, once daily for 12 weeks does not improve the severity of hot flash symptoms when compared with milk protein, with or without venlafaxine (90981).
• Asthma. It is unclear if oral soy reduces asthma symptoms. Details: One population study has found that people with asthma who consume soy foods providing more than 250 mcg of genistein for every 1000 kcal consumed (e.g., 500 mcg/day for 2000 kcal diet) daily have increased lung function, as measured by FEV1 scores, when compared to those who consume less (11084). However, clinical research in adult and pediatric patients with poorly controlled asthma shows that taking soy isoflavones 50 mg twice daily for 24 weeks does not improve FEV1 scores, reduce the number of asthma episodes, or improve asthma symptoms when compared with placebo (90977).
• Cardiovascular disease (CVD). It is unclear if soy consumption reduces the risk for CVD or CVD-related mortality. More research is needed to determine whether certain populations may benefit from increased soy intake. Details: Due to mixed findings, it is unclear if consuming soy is associated with a reduced risk of CVD events. One population study has found that consuming at least 60 grams of soy daily over a 12-month period is associated with a 14% reduced risk of having a CVD event over the next 5 years, as well as a reduced risk of stroke, when compared with consuming less than 15 grams daily (108253). A study in Japan has found that consuming soy five or more times per week over a 10-year period is associated with fewer adverse cardiovascular outcomes in only a certain subset of patients when compared with consuming soy twice a week or less. Postmenopausal adults with the highest consumption had a 36% lower risk of stroke, a 45% lower risk of myocardial infarction, and a 65% lower risk of CVD mortality. However, risk was not significantly reduced in males or premenopausal adults (17108). In contrast, a study in Korea has found that consuming a median of 16.5 servings of soy per week is associated with a 64% reduced risk of CVD incidence in premenopausal, but not postmenopausal, adults when compared with a median of 4.7 servings per week. A subgroup analysis has found that the highest intake of tofu, but not soybeans, fermented soy paste, or soy milk, is associated with a reduced incidence of CVD (108243). Additionally, higher dietary intake of soy does not seem to be associated with a reduced risk of cardiovascular events in Western females (13040). The amount of phytoestrogens typically consumed in Western diets is significantly lower than the amount typically consumed in Asian diets. The form of soy food and isoflavone content might play a role in these discrepancies. Any association between consumption of soy-containing foods and CVD mortality is also unclear. A meta-analysis of observational studies conducted in China or Japan has found that the highest intake of soy-containing foods is not associated with a lower risk of CVD-related mortality when compared with the lowest intake (96941). A population study in patients with or without a prior history of CVD has also found that soy-containing food consumption is not associated with a lower risk of CVD-related mortality when compared with the lowest intake (108244). However, some research has found a positive effect of soy consumption on CVD mortality risk. A subgroup analysis of a meta-analysis has found that the highest intake of fermented soy products is associated with a 16% reduced risk of CVD mortality; higher intake of non-fermented soy is not associated with CVD mortality (96941). Population research in patients without a prior history of CVD has found that soy-containing food consumption is associated with a lower risk of myocardial infarction-related mortality when compared with the lowest intake (108244). Also, one population study in adults with type 2 diabetes has found that consuming soy-containing foods at least four days each week is associated with a 23% reduced risk of CVD mortality when compared with never consuming soy foods. Consuming soy foods less than four times weekly is not associated with CVD-related mortality (108242).
• Cervical cancer. It is unclear if oral soy reduces the risk for cervical cancer. Details: Population research has found that the highest dietary intake of soy over approximately 17 years is associated with a 57% decreased risk of cervical cancer when compared to the lowest intake of soy in females who also drank green tea. However, neither soy intake nor green tea intake alone was associated with a decreased risk of cervical cancer. Additionally, other population research has not confirmed an association between soy intake and cervical cancer (101800).
• Child growth. It is unclear if oral soy protein enhances child growth. Details: Preliminary clinical research in Colombian children 2-7 years of age shows that consuming a soy protein supplement dissolved in fruit juice on 6 days of every week for 1 year does not improve body mass index, body composition, weight, or height when compared with consuming fruit juice and whole milk. A sub-analysis shows that children consuming the soy protein supplement had an increase in weight-for-age when compared with the control group, indicating that the supplement may be beneficial for ensuring adequate weight and nutritional status during prepubertal growth (100320). However, the children in this study had normal or below average weight-for-age at baseline, limiting the applicability of these findings to other patient populations.
• Cognitive function. It is unclear if oral soy improves cognitive function; research is conflicting. Details: Some research shows that college students who increase consumption of soy foods providing isoflavones 100 mg daily have improved short- and long-term memory (9671). Postmenopausal patients aged 50-65 years who take a soy extract supplement providing isoflavones 60 mg daily also seem to have some improvement in some measures of cognitive function (12048). There is also evidence in postmenopausal patients aged 55-75 years that taking a soy extract supplement providing isoflavones 110 mg daily might improve verbal memory scores (12040). However, another study in this population shows that consuming 25.6 grams daily of soy protein providing 99 mg of isoflavones does not improve cognitive function (12034). Similarly, population research in females aged 42-52 years has found that increasing dietary intake of the isoflavones genistein and daidzein is not associated with improved measures of cognitive function (15042). These differing findings might be explained by variations in study design and soy formulations.
• Cognitive impairment. Oral soy has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults 55 years of age and older with mild cognitive impairment shows that taking a specific combination product (DW2009) containing fermented soybean powder and Lactobacillus plantarum daily for 12 weeks modestly improves composite cognitive function when compared with placebo (100319). It is not clear if this effect is due to soy, lactobacillus, or the combination.
• Colic. It is unclear if oral soy is beneficial in infants with colic. Details: Preliminary clinical research shows that consuming soy-based formula might reduce the duration of colic symptoms in infants with cows' milk intolerance (75509,75543). However, other clinical research shows that consuming soy-based formula does not improve crying in infants with colic when compared with dicyclomine hydrochloride 3 mg/kg daily (75573). Also, a meta-analysis of only high quality clinical research shows that soy milk formula does not improve the persistence of colic or the duration of crying in infants with colic when compared with control (75611).
• Crohn disease. It is unclear if oral soy improves symptoms of Crohn disease. Details: A small observational study in patients with inactive Crohn disease has found that taking oral soy-derived protein in combination with enteral treatment for 4 weeks is associated with increased bowel movements, improved symptoms such as fatigue and mental strain, and increased body weight when compared with standard enteral treatment alone (75175).
• Diabetic nephropathy. It is unclear if oral soy improves kidney function in patients with diabetic nephropathy. Details: A meta-analysis of small clinical trials in patients with diabetic nephropathy shows that consuming soy products, such as soy protein and soy milk, modestly reduces proteinuria and blood urea nitrogen (BUN), as well as levels of total and low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose, when compared with animal protein or cow's milk. However, there was no effect on any measures of kidney function (108247). Some individual small clinical trials show that replacing dietary animal protein with soy protein reduces urinary albumin excretion in patients with diabetic nephropathy (7348,12555,12556). However, one small clinical study shows that consuming soy milk 240 mL daily for 4 weeks does not affect urinary creatinine, blood urea nitrogen, proteinuria, or glomerular filtration rate in patients with diabetic nephropathy (90966).
• Dyspepsia. Oral soy protein has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with mild or moderate dyspepsia shows that consuming 1 gram of toasted soy flour fermented with Lactobacillus delbrueckii up to three times daily for 3 weeks does not improve heartburn severity or frequency when compared with placebo (105599).
• Endometrial cancer. It is unclear if oral soy protein reduces the risk for endometrial cancer. Details: Most epidemiological research has found that increased soy intake is associated with a lower risk of endometrial cancer. Endometrial cancer incidence is lower in Japan, China, and other Asian countries where the typical diet is low in calories and high in soy, whole grain foods, vegetables, and fruits (7338,11036,90954). Also, a large meta-analysis of population research has found that the highest total and fermented soy intake is associated with a 17% to 19% reduced risk of developing endometrial cancer when compared to the lowest intakes in postmenopausal adults (96002). However, one clinical study shows that taking soy protein 25 grams daily providing 91 mg of aglycon equivalents of isoflavones and glycosides for three years does not reduce the risk of endometrial hyperplasia or cancer when compared with placebo in postmenopausal adults. However, this study may not have been adequately powered to detect small differences in the low rates of endometrial hyperplasia (90971).
• Fibromyalgia. It is unclear if oral soy reduces fibromyalgia symptoms. Details: Clinical research shows that consuming a shake containing soy protein 20 grams and soy isoflavone 160 mg once daily for 6 weeks does not improve physical functioning or symptoms of depression in patients with fibromyalgia when compared with placebo (75451).
• Gastric cancer. It is unclear if oral soy reduces the risk for gastric cancer. Details: Meta-analyses of population research have found that the highest intake of soy-containing foods and nonfermented soy products is associated with a 21% to 37% decreased risk of gastric cancer when compared with the lowest intake (95998,108246). Intake of at least 100 grams daily of nonfermented soy foods was found to be the most protective (95998). However, a high intake of fermented soy products is associated with an increased risk of gastric cancer, and intake of 1-5 cups daily of the fermented soy product miso soup is associated with an increased risk of gastric cancer in males (95998,108246).
• Hepatitis C. It is unclear if oral soy is beneficial for hepatitis C. Details: Preliminary clinical research in patients with hepatitis C shows that taking soy protein 32 grams daily for 12 weeks reduces the number of cases of steatosis by 47% and reduces alanine aminotransferase (ALT) levels by 13% when compared to baseline. However, it is no different than taking casein protein (90970).
• Irritable bowel syndrome (IBS). A small study suggests that oral soy isoflavones might reduce IBS symptoms. Details: A small clinical study in females with IBS shows that taking soy isoflavones 40 mg daily for 6 weeks improves symptoms of IBS, such as abdominal distention and abdominal pain severity and duration, by approximately 27% when compared with placebo. Quality of life is also improved. Some symptoms are also improved when soy isoflavones are taken in combination with vitamin D; however, the combination of soy isoflavones and vitamin D does not seem to improve symptoms better than soy isoflavones alone (96425).
• Lung cancer. It is unclear if dietary soy reduces the risk for lung cancer. Details: A meta-analysis of epidemiological research has found that although increased soy intake is not associated with a reduced risk of lung cancer overall, it is associated with a slightly reduced risk in nonsmoking adults (90985).
• Mastalgia. It is unclear if oral soy is beneficial for mastalgia. Details: A small clinical study suggests that soy milk providing 34 grams soy protein daily might reduce cyclical breast pain when compared with no intervention (2428).
• Migraine headache. Oral soy has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research 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 menstrual-associated migraine attacks when compared with placebo (35797). It is not clear if this effect is due to soy, the other ingredients, or the combination.
• Neonatal jaundice. It is unclear if oral soy reduces the risk of neonatal jaundice. Details: Clinical research shows that patients with gestational diabetes who consume a diet containing soy protein along with other plant and animal proteins for 6 weeks beginning at 24-28 weeks' gestation have a 73% reduced risk for newborn hyperbilirubinemia when compared with those consuming a control diet containing only non-soy plant and animal proteins (95993).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral soy is beneficial for the treatment or prevention of NAFLD. Details: Observational research in a Chinese population has found that increased frequency of dietary soy consumption is associated with a lower incidence of NAFLD when compared with lower consumption (105612). A meta-analysis of three small clinical trials in patients living in Iran with NAFLD shows that consuming soy milk, soy foods, or a genistein supplement for 8 weeks might reduce some liver transaminase levels when compared with control (105611). Another meta-analysis of small clinical trials in patients with NAFLD shows that consuming soy milk, soy foods, or a genistein supplement for 8 or 24 weeks modestly improves insulin resistance but does not improve body mass index, cholesterol levels, or liver transaminase levels (108239). These analyses are limited by their generally small population size and the heterogeneity of interventions.
• Obesity. It is unclear if consuming oral soy protein as part of a calorie-restricted diet improves weight loss; research is conflicting. Details: Some clinical research shows that consuming soy protein in conjunction with calorie restriction for 2-6 months helps reduce weight in those who are obese and overweight when compared with calorie restriction alone (11085,75397). Other clinical research shows that consuming soy protein for 16 weeks improves weight loss in overweight females when compared with consuming protein from meat (75620). Also, consuming black soy peptide 4.5 grams daily for 12 weeks reduces body weight and body fat mass more than placebo in overweight and obese adults (90961). In addition, some clinical evidence shows that eating biscuits supplemented with soy fiber 100 grams daily for 12 weeks reduces body weight, body mass index (BMI), and low-density lipoprotein (LDL) cholesterol when compared to control in overweight and obese patients (90960). However, contradictory evidence exists. Some clinical research shows that following a calorie-restricted diet and consuming soy-based meal replacements 3-5 times daily for 12-16 weeks, or eating soy protein-rich foods in place of animal protein for 2-12 weeks, does not improve weight loss in overweight or obese individuals when compared to a calorie-restricted diet alone (75277,75372,75376,90968). Also, in overweight and obese females following a free-choice diet, soy protein 56 grams daily for 23 weeks does not appear to improve weight loss when compared to eating an isoenergetic amount of carbohydrates (86077). Finally, a subgroup analysis of six preliminary clinical trials shows that soy products do not improve weight loss in postmenopausal adults (98870). The reason for these disparate findings is unclear but may be due to differences in the soy products used or differences in patient population. For example, a meta-analysis of clinical research shows that phytoestrogen consumption reduces weight in healthy postmenopausal adults but not in those with comorbid conditions (98870). However, the clinical validity of this analysis is limited because it did not evaluate the effect of soy-only phytoestrogens. Soy protein has also been compared with whey protein. One small clinical study in overweight and obese adults shows that patients taking soy protein isolate 52 grams for 23 weeks had similar overall weight and fat loss as those taking whey protein concentrate 52 grams daily (86077). In contrast, another small clinical study in overweight males shows that taking soy isolate 60 grams before lunch daily for 12 weeks is less effective for weight loss when compared with taking whey protein concentrate 65 grams (91801).
• Osteoarthritis. It is unclear if oral soy protein reduces osteoarthritis pain. Details: Preliminary clinical research shows that taking soy protein 40 grams daily for three months improves range of motion, pain, and quality of life in osteoarthritis patients, particularly males, when compared to baseline. However, these beneficial effects seem to also be observed following supplementation with milk-based protein, indicating that the benefits may have resulted from a placebo effect (75266).
• Overall mortality. It is unclear if dietary soy reduces overall mortality; the available research is conflicting. Details: A meta-analysis of observational studies has found that the highest intake of soy products is not associated with a lower risk of overall mortality, mortality from cardiovascular disease, or mortality from cancer when compared with the lowest intake (96941). However, a more recent population study has found that consuming at least 60 grams of soy daily over a 12-month period is associated with a 17% reduced risk of overall mortality over the next 5 years when compared with consuming less than 15 grams daily (108253). Also, an observational study in Japanese patients followed over 14.8 years has found that although overall soy intake is not associated with any benefit, increased intake of fermented soy products, such as natto and miso, was found to be associated with a slightly reduced risk of mortality (105600).
• Polycystic ovary syndrome (PCOS). It is unclear if oral soy reduces PCOS symptoms. Details: Clinical research shows that taking soy isoflavones 50 mg daily for 12 weeks improves insulin levels and insulin resistance by a small amount when compared with placebo in patients with PCOS. Furthermore, taking soy isoflavones improves the free androgen index by approximately 25% and triglyceride levels by 14% when compared to baseline. However, taking soy isoflavones does not improve low- or high-density lipoprotein (LDL or HDL) cholesterol levels or markers of inflammation (95994).
• Postmenopausal conditions. It is unclear if oral soy is beneficial for postmenopausal conditions. Details: A meta-analysis of generally small clinical trials in postmenopausal adults shows that taking soy protein with isoflavones or soy isoflavones, usually for 3-24 months, has modest beneficial effects on total cholesterol, and possibly high-density lipoprotein (HDL) cholesterol, when compared with milk protein, soy protein without isoflavones, or placebo. However, there was no effect on low-density lipoprotein (LDL) cholesterol or triglyceride levels. Subgroup analyses show that reductions in LDL cholesterol levels occur when soy is used for less than 6 months, in individuals older than 55 years, and when the soy protein contains isoflavones (108249).
• Preterm labor. It is unclear if oral soy reduces the risk for preterm labor. Details: Clinical research in patients with gestational diabetes shows that consuming a diet containing soy protein along with other plant and animal proteins for 6 weeks, beginning at 24-28 weeks' gestation, does not reduce the likelihood for caesarean section, preterm delivery, or maternal hospitalization when compared with a control diet containing only non-soy plant and animal proteins (95993).
• Premenstrual syndrome (PMS). It is unclear if oral soy reduces PMS symptoms. Details: Preliminary clinical research in patients with PMS shows that taking isolated soy protein containing soy isoflavones 68 mg daily for two menstrual cycles reduces cramps and swelling when compared with placebo (75279).
• Prostate cancer. It is unclear if oral soy is beneficial for the treatment or prevention of prostate cancer; research is conflicting. Details: Observational and clinical research has evaluated the effects of soy intake on prostate cancer risk. Observational research has found that consuming an Asian diet, which contains 10 times more soy than the average American diet, is associated with a lower risk of prostate cancer; however, it is unclear whether it is the soy content of the diet or if genetic differences or environmental factors such as fat ingestion are responsible for this correlation (2298,12884,12886,12887). A meta-analysis of observational trials from North America, Europe, and Asia has found that highest intake of total soy foods, unfermented soy foods, or soy isoflavones is associated with a reduced risk of prostate cancer when compared with the lowest intakes. However, higher intake of fermented soy foods is not associated with a reduced risk (96939). Furthermore, some observational research in Japanese males has found a weak association between increased prostate cancer mortality and a higher dietary intake of soy isoflavones when compared with a lower intake (105607). Research evaluating the use of soy supplements is also conflicting. One clinical study shows that taking soy protein 40 grams daily for 6 months reduces the development of prostate cancer six-fold in those at risk of prostate cancer when compared with milk protein (75432). However, another clinical study in healthy adults aged 50-80 years shows that taking soy protein, providing 83 mg isoflavones, daily for a year does not affect PSA levels when compared with a soy protein drink without isoflavones (12888). Soy products have also been evaluated in patients with prostate cancer. One clinical study shows that consuming a specific bread containing 50 grams of soy, providing 117 mg isoflavones, reduces PSA levels after about 3 weeks of treatment when compared with control (13140). Other preliminary clinical research in patients with rising PSA levels following prior therapy for prostate cancer shows that consuming 8 ounces of soy milk, standardized to contain 47 mg isoflavones, three times daily for 12 months slows the increase in PSA levels from 56% to 20% when compared with baseline (75435). However, one clinical study shows that taking soy protein 40 grams daily for 6 months does not reduce prostate size or improve PSA levels in those diagnosed with prostate cancer when compared with milk protein (75432). Also, in those with early stage prostate cancer, consuming a soy beverage daily providing genistein 60 mg does not seem to affect risk factors for progression of prostate cancer, including testosterone, estradiol, PSA, and sex hormone binding globulin (SHBG) levels (11033). Furthermore, consuming soy protein isolate 20 grams standardized to contain approximately 70 mg isoflavones daily for two years does not prevent prostate cancer recurrence following radical prostatectomy when compared with placebo (90953). Reasons for the discrepancies are not entirely clear, but may include the relatively short trial durations (up to 12 months) and heterogeneity of soy preparations and dosing regimens.
• Rheumatoid arthritis (RA). It is unclear if oral soy reduces RA symptoms. Details: Preliminary clinical research in patients with RA shows that consuming a liquid diet containing hydrolyzed soy protein (Top Up) daily for 4 weeks does not improve pain intensity, morning stiffness, or joint swelling and tenderness when compared to consuming a normal daily diet (75619).
• Sarcopenia. It is unclear if oral soy reduces age-related muscle loss; evidence is conflicting. Details: Some clinical research in postmenopausal adults shows that consuming soy protein containing isoflavones 99 mg daily for 12 months does not improve hand grip strength or physical performance when compared with a milk protein placebo (75283). However, another small clinical study in older adults with low muscle mass living in China shows that taking soy, or a whey-soy blended protein, 16 grams daily for 6 months, slightly attenuates muscle loss when compared with no intervention (105603).
• Stroke. It is unclear if oral soy improves outcomes and overall function in people who have had a stroke. Details: One small clinical study shows that older adults with a history of stroke who consumed soy milk 500 mL daily while participating in a rehabilitation program had greater improvements in hand grip strength, 8-feet walking speed, walking performance, and 6-minute walk test after 8 weeks when compared with placebo. However, consuming soy milk did not lead to greater improvements in lean mass or overall short physical performance battery (SPPB) scores when compared with placebo (100321).
• Thyroid cancer. It is unclear if dietary soy reduces the risk for thyroid cancer. Details: Epidemiological research has found that high dietary intake of soy is associated with a reduced risk of thyroid cancer when compared with lower intake (7662,12041).
• Vaginal atrophy. It is unclear if topical soy improves vaginal atrophy. Details: A small clinical study in postmenopausal adults with vaginal atrophy shows that applying one gram of soy extract 4% vaginal gel daily for 12 weeks reduces vaginal dryness and pain during sexual intercourse and improves vaginal endometrial thickness when compared with placebo (90964).
• Wrinkled skin. Small studies suggest that oral and topical soy might reduce wrinkles. Details: A small clinical study in middle-aged females shows that consuming soy isoflavone 40 mg daily for 12 weeks improves skin elasticity and the appearance of fine wrinkles when compared with placebo (75388). Another small clinical study in females with photodamaged skin shows that applying a soy moisturizer containing soybean trypsin inhibitor and Bowman-Birk protease inhibitor (Aveeno Positively Radiant Daily Moisturizer, Johnson & Johnson CCI) twice daily for 12 weeks improves skin pigmentation, fine lines, texture, tone, and appearance when compared with a placebo moisturizer (75410). More evidence is needed to rate soy for these uses.

(Read more about SOY)

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.

(Read more about WILD YAM)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Ashwagandha has been used with apparent safety in doses of up to 1250 mg daily for up to 6 months (3710,11301,19271,90649,90652,90653,97292,101816,102682,102683) (102684,102685,102687,103476,105824,109586,109588,109589,109590). ...when used topically. Ashwagandha lotion has been used with apparent safety in concentrations up to 8% for up to 2 months (111538).

PREGNANCY: LIKELY UNSAFE
when used orally. Ashwagandha has abortifacient effects (12).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about ASHWAGANDHA)

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)

POSSIBLY SAFE ...when used orally and appropriately, short term. Total glucosides of peony has been used with apparent safety in doses of up to 1800 mg daily for up to 12 months (92786,97949,97950,98466,100992,110432,112861,112862). Peony root extract has been used with apparent safety at a dose of 2250 mg daily for up to 3 months (97216). There is insufficient reliable information available about the safety of peony when used orally, topically, or rectally, long-term.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Total glucosides of peony has been used with apparent safety in children 1.5-4 years of age at doses up to 180 mg/kg daily or 1.2 grams daily for up to 12 months (92785). Peony root extract 40 mg/kg daily has also been used with apparent safety in children 1-14 years of age for 4 weeks (106851).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Preliminary research suggests that peony can cause uterine contractions (13400). However, other preliminary research suggests a combination of peony and angelica with or without motherwort, banksias rose, and ligustica, might be safe (11015,48433). Until more is known, avoid use.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about PEONY)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Sage is approved for use as a food in the United States (4912).

POSSIBLY SAFE ...when used orally in medicinal doses, short-term. Common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) have been used with apparent safety when taken orally in doses of 280 mg daily for up to 8 weeks (10334,10810,17177,105338). ...when used topically. Common sage (Salvia officinalis) has been used with apparent safety as a single agent or in combination products for up to one week (10437,72619,107023). ...when the essential oil is inhaled as aromatherapy, short-term (72658).

POSSIBLY UNSAFE ...when used orally in high doses or long-term (12,1304). Some species of sage, including common sage (Salvia officinalis), contain a thujone constituent that can be toxic if consumed in large enough quantities (12,1304).

PREGNANCY: LIKELY UNSAFE
when used orally. The constituent thujone can have menstrual stimulant and abortifacient effects (19).

LACTATION: POSSIBLY UNSAFE
when used orally; sage is thought to reduce the supply of mother's milk (19).

(Read more about SAGE)

LIKELY SAFE ...when soy protein is used orally and appropriately. Soy protein products in doses up to 60 grams, providing up to 185 mg isoflavones, daily have been safely used in studies lasting up to 16 weeks (842,2293,2294,2296,3025,3402,3977,4755,6412,8530)(10372,11805).

POSSIBLY SAFE ...when soy extracts are used orally and appropriately, short-term. Soy extracts containing concentrated isoflavones in doses of 35-120 mg daily have been used with apparent safety for up to 6 months (4751,6455,7802,12040,12048,13209,95994,95999).

CHILDREN: LIKELY SAFE
when consumed in amounts commonly found in foods or as a component of infant formula (3400,4912,7331). Soy milk that's not designed for infants should not be used as a substitute for infant formula. Regular soy milk can lead to nutrient deficiencies (12045). Most evidence shows that exposure to soy formula or other soy products in infancy does not cause early onset of puberty or health or reproductive problems later in life (7331,11080,108245). However, some small cohort studies have suggested that higher soy intake during childhood may be associated with an increased risk of precocious puberty (108240) and may be weakly correlated with the development of breasts in children less than 2 years of age (75520). This is in contrast to an observational study in Chinese children ages 7-9 years which suggests that higher soy intake is associated with delayed puberty (108252). One small cohort study has also found that use of soy infant formula may be associated with an increased risk of endometriosis in adulthood, although endometriosis was also correlated with prematurity, which may have confounded the findings (101803).

CHILDREN: POSSIBLY UNSAFE
when used orally as an alternative to cow's milk in children with severe milk allergy (75359). Although soy protein-based infant formulas are often promoted for children with milk allergy, children with a severe allergy to cow's milk are also frequently sensitive to soy protein (9883). There is insufficient reliable information available about the safety of soy products when used in amounts higher than typical food quantities for children.

PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (4912).

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Soy contains mildly estrogenic constituents (3373,3988,3989,3990,3994,6029,75303). Theoretically, therapeutic use of soy might adversely affect fetal development; avoid using.

LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (4912). A single 20-gram dose of roasted soybeans, containing 37 mg isoflavones, produces four to six times less isoflavones in breast milk than provided in a soy-based infant formula (2290). There is insufficient reliable information available about the safety of long-term use of therapeutic amounts of soy during lactation.

(Read more about SOY)

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.

(Read more about WILD YAM)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking ashwagandha with antidiabetes drugs might increase the risk of hypoglycemia.  Details There is preliminary clinical evidence suggesting that ashwagandha might lower blood glucose levels. Theoretically, ashwagandha might have additive effects when used with antidiabetes drugs and increase the risk of hypoglycemia (19274,90649,102685).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha with antihypertensive drugs might increase the risk of hypotension.  Details Animal research suggests that ashwagandha might lower systolic and diastolic blood pressure (19279). Theoretically, ashwagandha might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.

BENZODIAZEPINES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha might increase the sedative effects of benzodiazepines.  Details There is preliminary evidence that ashwagandha might have an additive effect with diazepam (Valium) and clonazepam (Klonopin) (3710). This may also occur with other benzodiazepines.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha might increase the sedative effects of CNS depressants.  Details Ashwagandha seems to have sedative effects. Theoretically, this may potentiate the effects of barbiturates, other sedatives, and anxiolytics (3710).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha might decrease the effects of immunosuppressants.  Details Ashwagandha has demonstrated immunostimulant effects in humans (3710,3711,4114,11301,106786). Animal research has shown that ashwagandha can attenuate the immunosuppression caused by cyclophosphamide (3711,4114).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Ashwagandha might increase the effects and adverse effects of thyroid hormone.  Details Concomitant use of ashwagandha with thyroid hormones may cause additive therapeutic and adverse effects. Preliminary clinical research and animal studies suggest that ashwagandha boosts thyroid hormone synthesis and secretion (19281,19282,97292). In one clinical study, ashwagandha increased triiodothyronine (T3) and thyroxine (T4) levels by 41.5% and 19.6%, respectively, and reduced serum TSH levels by 17.4% from baseline in adults with subclinical hypothyroidism (97292).

(Read more about ASHWAGANDHA)

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)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining peony with anticoagulant or antiplatelet drugs might increase the risk of bleeding.  Details In vitro research suggests that peony might have antiplatelet, anticoagulant, and antithrombotic effects (92787).

CLOZAPINE (Clozaril) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peony might increase the levels and clinical effects of clozapine.  Details In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on cytochromes P450 (CYP) 1A2 and CYP3A4 (92790). This effect has not been reported in humans.

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, peony might interfere with contraceptive drugs due to competition for estrogen receptors.  Details In vitro and animal research shows that peony extract has estrogenic activity (100990). Concomitant use might also increase the risk for estrogen-related adverse effects.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.  Details In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP3A4.  Details In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of large amounts of peony might interfere with hormone replacement therapy and/or increase the risk for estrogen-related adverse effects.  Details In vitro and animal research shows that peony extract has estrogenic activity (100990). Theoretically, peony might compete for estrogen receptors and/or cause additive estrogenic effects.

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, peony might reduce the levels and clinical effects of phenytoin.  Details Animal research shows that taking peony root reduces levels of phenytoin (8657). Some researchers suggest that peony root might affect cytochrome P450 (CYP) 2C9, which metabolizes phenytoin. However, preliminary research in humans shows that peony root does not alter levels of losartan (Cozaar), which is also metabolized by CYP2C9 (11480).

(Read more about PEONY)

ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might decrease the clinical effects of anticholinergic drugs.  Details In vitro evidence suggests that common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) can inhibit acetylcholinesterase and might increase acetylcholine levels (31438,39566,72603,72616).

ANTICONVULSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might interfere with the clinical effects of anticonvulsant drugs.  Details Some species of sage can cause convulsions when consumed in large quantities (10812).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking sage with antidiabetes drugs might increase the risk of hypoglycemia.  Details In patients with polycystic ovary syndrome (PCOS) or inadequately controlled type 2 diabetes, common sage (Salvia officinalis) has demonstrated hypoglycemic activity (91971,103380). However, other clinical research in patients with inadequately controlled type 2 diabetes shows that common sage extract does not lower fasting blood glucose levels (105340).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase or decrease the effects of antihypertensive drugs.  Details Animal research suggests that common sage (Salvia officinalis) can cause prolonged blood pressure reduction (4152). However, clinical research suggests that Spanish sage (Salvia lavandulaefolia) can increase blood pressure in some people with hypertension (10334). Until more is known, use with caution.

BENZODIAZEPINES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking sage might increase the sedative and adverse effects of benzodiazepines.  Details In vitro evidence suggests that certain components of common sage (Salvia officinalis) can bind to benzodiazepine receptors (72588). This effect has not been reported in humans.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might have additive effects when used with cholinergic drugs.  Details In vitro evidence suggests that common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) can inhibit acetylcholinesterase and might increase acetylcholine levels (31438,39566,72603,72616).

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.  Details Some constituents of sage have CNS depressant activity (10334).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C19.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C19 (10848). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C9.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C9 (10848). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2D6.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2D6 (10848,19430). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might decrease the levels and clinical effects of drugs metabolized by CYP2E1.  Details Animal research suggests that drinking common sage (Salvia officinalis) tea increases the expression of CYP2E1 (72627). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP3A4.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP3A4 (10848,72641). So far, this interaction has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might interfere with hormone therapy.  Details In vitro evidence suggests that geraniol, a constituent of Spanish sage (Salvia lavandulaefolia), exerts estrogenic activity (39572). The clinical significance of this effect is unclear.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase levels of drugs transported by P-glycoprotein.  Details In vitro research suggests that common sage (Salvia officinalis) can inhibit the multi-drug transporter protein, P-glycoprotein (72641). This effect has not been reported in humans.

(Read more about SAGE)

ANTIBIOTIC DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, antibiotics may decrease the activity of soy isoflavones.  Details Intestinal bacteria are responsible in part for converting soy isoflavones into their active forms. Antibiotics may decrease the amount of intestinal bacteria and decrease its ability to convert isoflavones (7657).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = A Soy can lower blood glucose and have additive effects with antidiabetes drugs.  Details Clinical research shows that whole soy diets and soy-based meals reduce fasting glucose levels in diabetic and non-diabetic individuals (75268,75296,75378,75493,96001). Also, individuals following a soy-based meal replacement plan seem to require lower doses of sulfonylureas and metformin to manage blood glucose levels when compared with individuals following a diet plan recommended by the American Diabetes Association (75268).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = A Theoretically soy protein may have additive effects with antihypertensive drugs and increase the risk of hypotension.  Details Although some contradictory research exists (14254), most clinical evidence suggests that consuming soy protein modestly reduces systolic and diastolic blood pressure in individuals with prehypertension or hypertension (13139,75482).

CAFFEINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, soy might reduce the clearance of caffeine.  Details Soy contains genistein. Taking genistein 1 gram daily for 14 days seems to inhibit caffeine clearance and metabolism in healthy females (23582). This effect has been attributed to inhibition of the cytochrome P450 1A2 (CYP1A2) enzyme, which is involved in caffeine metabolism. It is unclear if this effect occurs with the lower amounts of genistein found in soy.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Soy might modestly induce CYP2C9 enzymes. However, this effect does not seem to be clinically significant.  Details In vitro research suggests that an unhydrolyzed soy extract might induce CYP2C9. However, the significance of this interaction is likely minimal. In healthy females taking a specific extract of soy (Genistein Soy Complex, Source Naturals), blood levels of losartan, a CYP2C9 substrate, were not significantly affected (16825).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, soy might have additive effects when used with diuretic drugs.  Details Animal research suggests that genistein, a soy isoflavone, increases diuresis within 6 hours of subcutaneous administration in rats. The effects seem to be similar to those of furosemide (75604). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, soy might competitively inhibit the effects of estrogen replacement therapy.  Details Soy contains phytoestrogens and has been shown to have estrogenic activity in some patients (3860). Although this has not been demonstrated in humans, theoretically, concomitant use of soy with estrogen replacement therapy might reduce the effects of the estrogen replacement therapy.

LEVOTHYROXINE (Synthroid, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Soy products might reduce the absorption of levothyroxine in some patients.  Details Preliminary clinical research and a case report suggest that soy-based formulas inhibit the absorption of levothyroxine in infants with congenital hypothyroidism (20636,20637,75548,90959). A levothyroxine dosage increase may be needed for infants with congenital hypothyroidism while using soy-based formulas, and the dose may need to be reduced when soy-based formulas are no longer administered. However, in postmenopausal adults, clinical research shows that taking a single dose of soy extract containing isoflavones 60 mg along with levothyroxine does not affect the oral bioavailability of levothyroxine (95996).

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = C Taking soy products containing high amounts of tyramine along with MAOIs can increase the risk of hypertensive crisis.  Details Fermented soy products such as tofu and soy sauce contain tyramine, a naturally occurring chemical that affects blood pressure regulation. The metabolism of tyramine is decreased by MAOIs. Consuming more than 6 mg of tyramine while taking an MAOI can increase the risk of hypertensive crisis (15649). The amount of tyramine in fermented soy products is usually less than 0.6 mg per serving; however, there can be significant variation depending on the specific product used, storage conditions, and length of storage. Storing one brand of tofu for a week can increase tyramine content from 0.23 mg to 4.8 mg per serving (15649,15701,15702). Advise patients taking MAOIs to avoid fermented soy products that contain high amounts of tyramine.

PROGESTERONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = A Theoretically, combining soy isoflavones with transdermal progesterone may worsen bone density.  Details Clinical research suggests that significant bone loss may occur in females with osteoporosis who receive a combination of transdermal progesterone with soy milk containing isoflavones when compared with placebo, soy milk alone, or progesterone alone (69859).

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, estrogenic soy isoflavones might alter the effects of tamoxifen.  Details Laboratory research suggests that genistein and daidzen, isoflavones from soy, can antagonize the antitumor effects of tamoxifen under some circumstances (7072,14362,8966); however, soy isoflavones might have different effects when used at different doses. A relatively low in vitro concentration of soy isoflavones such as 1 microM/L seems to interfere with tamoxifen, whereas high in vitro concentrations such as those >10 microM/L might actually enhance tamoxifen effects. People on a high-soy diet have soy isoflavones levels ranging from 0.1-6 microM/L. Until more is known, advise patients taking tamoxifen to avoid therapeutic use of soy products.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, soy might interfere with the effects of warfarin.  Details Soy milk has been reported to decrease the international normalized ratio (INR) in a patient taking warfarin. The mechanism of this interaction is not known (9672). However, animal and in vitro research suggests that soy may also inhibit platelet aggregation (3992). Dosing adjustments for warfarin may be necessary.

(Read more about SOY)

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.

(Read more about WILD YAM)

General ...Orally, ashwagandha seems to be well-tolerated. Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal upset, nausea, and vomiting. However, these adverse effects do not commonly occur with typical doses.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about acute liver failure, hepatic encephalopathy, and the need for liver transplantation with ashwagandha treatment.

Dermatologic ...Orally, dermatitis has been reported in three of 42 patients in a clinical trial (19276).

Endocrine ...A case report describes a 73-year-old female who had taken an ashwagandha root extract (unspecified dose) for 2 years to treat hypothyroidism which had been previously managed with levothyroxine. The patient was diagnosed with hyperthyroidism after presenting with supraventricular tachycardia, chest pain, tremor, dizziness, fatigue, irritability, hair thinning, and low thyroid stimulating hormone (TSH) levels. Hyperthyroidism resolved after discontinuing ashwagandha (108745).

Gastrointestinal ...Orally, large doses may cause gastrointestinal upset, diarrhea, and vomiting secondary to irritation of the mucous and serous membranes (3710). When taken orally, nausea and abdominal pain (19276,110490) and gastritis and flatulence (90651) have been reported.

Genitourinary ...In one case report, a 28-year-old male with a decrease in libido who was taking ashwagandha 5 grams daily over 10 days subsequently experienced burning, itching, and skin and mucous membrane discoloration of the penis, as well as an oval, dusky, eroded plaque (3 cm) with erythema on the glans penis and prepuce (32537).

Hepatic ...Orally, ashwagandha in doses of 154-1350 mg daily has played a role in several case reports of liver injury. In most of these cases, other causes of liver injury were excluded, and liver failure did not occur. Symptoms included jaundice, pruritus, malaise, fatigue, lethargy, weight loss, nausea, diarrhea, abdominal pain, stool discoloration, and dark urine. Symptom onset was typically 5-180 days from first intake, although in some cases onset occurred after more than 12 months of use (102686,107372,110490,110491,111533,111535,112111). Laboratory findings include elevated aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, and serum bilirubin (112111). In most cases, liver enzymes normalized within 1-5 months after discontinuation of ashwagandha (102686,107372,110491,111535,112111). However, treatment with corticosteroids, lactulose, ornithine, ursodeoxycholic acid, and plasmapheresis, among other interventions, was required in one case (111533). Rarely, use of oral ashwagandha has been reported to cause hepatic encephalopathy and liver failure requiring liver transplantation (110490).

Neurologic/CNS ...Orally, ashwagandha has been reported to cause drowsiness (110492). Headache, neck pain, and blurry vision have been reported in a 47-year-old female taking ashwagandha, cannabis, and venlafaxine. Imaging over the course of multiple years and hospital admissions indicated numerous instances of intracranial hemorrhage and multifocal stenosis of intracranial arteries, likely secondary to reversible cerebral vasoconstriction syndrome (RCVS) (112113). It is unclear whether the RCVS and subsequent intracranial hemorrhages were precipitated by ashwagandha, cannabis, or venlafaxine.

(Read more about ASHWAGANDHA)

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, peony seems to be well tolerated when used alone and as part of Chinese herbal formulas.
Most Common Adverse Effects:
Orally: Abdominal distension, anorexia, diarrhea, gastrointestinal discomfort, nausea.
Topically: Dermatitis.

Dermatologic ...Topically, peony has been reported to cause contact dermatitis (13555).

Endocrine ...Orally, a specific traditional Chinese medicine preparation called DDT has been reported to lower follicle-stimulating hormone (FSH) levels and increase estradiol levels. It is not known if this effect is due to peony or the other ingredients (48404). Another specific traditional Chinese medicine preparation, Toki-shakuyaku-san, has been reported to increase plasma progesterone levels in some patients. It is not known if this effect is due to peony or the other ingredients (15294).

Gastrointestinal ...Orally, peony and total glucosides of peony (TGP) have been reported to cause gastrointestinal discomfort, including abdominal distension, anorexia, diarrhea, and nausea, in some patients (13538,92785,97949,98466,100992). In one clinical study, diarrhea was reported in 5% of patients taking TGP 600 mg three times daily for 24 weeks versus 1% of patients taking placebo (100992).

Hematologic ...Orally, there is one case report of easy gum bleeding, epistaxis, and skin bruising with an international normalized ratio (INR) above 6 in a 61-year-old male who was previously stable on warfarin therapy. This patient had switched from one brand of quilinggao, a popular Chinese herbal product, to another brand 5 days prior. This product contained Fritillaria spp. (beimu), Paeonia rubra, Chinese peony (chishao), Lonicera japonica (jinyinhua), and Poncirus trifoliata (jishi). The patient's INR decreased to 1.9 after temporary withdrawal of warfarin therapy. Upon re-initiation of quilinggao, his INR increased to 5.2. It is not known if the increased INR is due to peony or the other ingredients (68343).

(Read more about PEONY)

General ...Orally, topically, and when inhaled, sage seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, agitation, diarrhea, dizziness, nausea, and vomiting.
Topically: Burning, dermatitis, pain.
Serious Adverse Effects (Rare):
Orally: Generalized tonic-clonic seizures associated with the thujone, camphor, and/or cineol constituents.

Cardiovascular ...By inhalation, sage essential oil has been reported to increase the blood pressure of hypertensive patients (10334).

Dermatologic ...Orally, sage extract has been reported to cause acneiform skin eruptions in one patient in a clinical trial (91970).
Topically, sage leaves can cause contact dermatitis (46902,72661,72710). Sage extract can cause burning and pain (10437).

Gastrointestinal ...Orally, sage can cause nausea, vomiting, abdominal pain, and diarrhea (10810,17177).
Topically, sage extract sprayed into the mouth and throat can cause dryness or mild burning of the throat (72619).

Neurologic/CNS ...Orally, sage can cause dizziness or agitation (10810,17177). Thujone, a constituent of common sage (Salvia officinalis), is a neurotoxin and can cause seizures (10812,12868). Camphor and cineol, constituents of common sage and Spanish sage, can also cause neurotoxicity and seizures in high doses (10334,12868). Generalized tonic-clonic seizures have been reported in adults, children, and infants after ingestion of sage oil (12868,72666).

Pulmonary/Respiratory ...Orally, sage can cause wheezing (10810,17177).
Occupational exposure to sage dust can cause reduction in ventilatory capacity and chronic respiratory impairment (72672,72682,72686).

(Read more about SAGE)

General ...Orally, soy is well tolerated.
Most Common Adverse Effects:
Orally: Bloating, constipation, diarrhea, and nausea.
All ROAs: Allergic reactions.

Endocrine ...In the 1950s and 1960s, cases of altered thyroid function, particularly goiter, were reported in children taking soy formula. However, adding iodine to soy formula or replacing soy flour in formula with soy protein isolate has nearly eliminated the risk of altered thyroid function in most infants (75353,75651).
In adults, there is some evidence that soy intake can alter thyroid function. Results from one clinical trial suggests that consuming soybeans 30 grams daily for as little as one month can increase thyroid-stimulating hormone (TSH) and decrease thyroxine, causing diffuse goiters, constipation, fatigue, and lethargy in some Japanese men. Recovery was achieved by discontinuing soybean intake (75206,75353). There is also some evidence that soy inhibits thyroid hormone synthesis resulting in increased secretion of TSH in some postmenopausal patients (7806). However, this seems to only occur in people with iodine deficiency (6466,75311). In postmenopausal patients with normal levels of iodine, taking a soy extract for 6 months does not seem to significantly affect thyroid hormone levels (13010).
Evidence from a single case-control study suggests that consumption of soy-based formulas may be associated with an observed three-fold increase in the risk of breast development in Puerto Rican children less than 2 years-old (75520). The correlation has been attributed to the estrogenic activity of soy. However, other risk factors, including a maternal history of ovarian cysts and consumption of meat products were also associated with the increased risk of breast development prior to 2 years of age. Also, the investigators noted that in over half of the cases, the child had not been exposed to soy or any of the other risk factors. Therefore, factors other than soy consumption may be more strongly associated with the increased risk of breast development prior to 2 years of age.

Gastrointestinal ...Gastrointestinal upset, such as constipation, diarrhea, bloating, and nausea are the most common side effects of soy (2297,11033,11082,15851,75491,95999). Reports of "bad taste" and taste intolerance have also been documented in clinical research (15851,39007,75491). Firmer stools, diarrhea, colitis, and intestinal mucosal damage has been reported in infants fed soy protein formula (75161,75448,75516,75525).

Genitourinary ...Orally, soy might increase discomfort during menstrual periods. Evidence from a small, retrospective cohort study has found that consuming soy formula as an infant may slightly increase the duration and discomfort of menstrual periods later in life. However, the investigators noted that these differences may not be clinically significant (7331).
Orally, frequent soy consumption might be a risk factor for uterine leiomyoma, an estrogen-dependent benign tumor located on the uterus. Observational research found that consumption of soy milk or soybean at least four times weekly is associated with a 7-fold increased odds of uterine leiomyoma (98869).
There is some concern that use of soy-based formulas in infants might result in long-term health complications. However, results from a retrospective cohort study has found that intake of soy-based formula as an infant does not affect height, weight, body mass index, pubertal maturation, menstrual history, or pregnancy history, nor does it increase the risk of reproductive organ disorders, hormonal disorders, libido dysfunction, or birth defects in the offspring of adults who received soy formula as infants (7331,11080). Additionally, research in adults shows that urinary phytoestrogens are not associated with endometriosis risk (101804). However, some population research has found that regular exposure to soy-based formulas during infancy is associated with an increased risk for endometriosis (101803).

Immunologic ...Orally, soy can cause allergic reactions such as skin rash and itching in some people (6412). In an 11-year-old female, allergy to soy protein resulting in a delayed itching papular rash was thought to be responsible for the reaction to injected benzathine benzylpenicillin containing possible soy protein-contaminated soy lecithin (96422).
Topically, soy-based ingredients were responsible for the development of hand atopic dermatitis in a young female using cosmetic lotions in the workplace. Percutaneous sensitization resulted in the development of anaphylaxis to oral soy (96000).

Neurologic/CNS ...Orally, one clinical study showed that insomnia was more common in postmenopausal adults taking soy isoflavone supplements when compared with those receiving placebo (9917). Some research suggests that dietary consumption of tofu during midlife might decrease cognitive function in later years. Evidence from one retrospective cohort study suggests that males who consume at least two servings of tofu weekly during midlife have increased risk of cognitive impairment in late life (19% vs. 4%) compared to those who consume tofu less frequently. Although the effect of tofu was considered to be marginal compared to other factors such as age, education, or history of stroke, results from the study suggest that the effect of significant midlife consumption of tofu is comparable to the effect of an age difference of 4 years or an education difference of 3 years. However, numerous other factors, such as lifestyle and health, could be involved (6415,6416). Therefore, these findings are too preliminary to be used as a basis for clinical recommendations.

Oncologic ...There is controversy about the role of soy in breast cancer. Population studies suggest that soy is protective against breast cancer. Asian females who eat a traditional diet high in soy seem to have a lower risk of developing breast cancer (4590,5939,9674). Early exploratory studies have suggested that soy stimulates proliferation of normal human breast tissue (3980,3981). However, taking a soy tablet containing 50 mg soy isoflavones daily for 12 months does not alter mammographic or breast MRI tissue density in adults at high risk of breast cancer, with non-endocrine treated breast cancer, or previously treated for breast cancer and without evidence of recurrence (95999).
There is some concern that soy supplements, but not soy foods, might increase the risk of endometrial hyperplasia due to its estrogenic effects. Population and clinical research suggests that soy foods do not have a proliferative effect on endometrial cells (7358,2429,7654,9676,9917), and increased dietary soy and phytoestrogens are associated with reduced endometrial cancer risk (7338,10372). However, the effects seem to be different with concentrated soy isoflavone extract. While taking products providing isoflavones 120 mg daily for 6 months does not increase endometrial thickening (13209), taking higher doses such as isoflavones 150 mg daily for 5 years might increase the risk of simple endometrial hyperplasia (12105). However, there is no evidence that soy isoflavones increase the risk of atypical hyperplasia which has a much higher risk of developing into endometrial cancer than simple endometrial hyperplasia (12105,90973).
There is also concern that increased soy intake increases the risk for other types of cancer. Some observational research has found that higher dietary intake of soy is associated with a higher risk for bladder cancer and pancreatic cancer (9677,105609).
A meta-analysis of results from cohort and case-control studies evaluating the risk of stomach cancer related to consumption of fermented soy products is unclear and inconclusive. The highest quality data from cohort studies suggests that these products have no significant effect on stomach cancer (7340,7341). More research is required to determine if soy products have any correlation with stomach cancer.

Pulmonary/Respiratory ...Inhaled soy dust and soy hull aeroallergen can trigger symptoms of asthma and allergic rhinitis (5084,5085,5086).

(Read more about SOY)

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).

(Read more about WILD YAM)