Cell Block 80 [Discontinued] by Clean Machine

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)

LIKELY EFFECTIVE

• Boron deficiency. Oral boron treats and prevents boron deficiency. Details: Taking boron orally is effective for preventing and treating boron deficiency (7135).

POSSIBLY EFFECTIVE

• Radiation dermatitis. Topical application of sodium pentaborate pentahydrate gel to radiation sites may reduce the risk of dermatitis in patients with breast cancer who are receiving radiotherapy. Details: A small clinical study in patients with breast cancer shows that applying a hydrogel containing sodium pentaborate pentahydrate 3% four times daily during radiotherapy for 5 weeks reduces the risk of moderate to severe dermatitis by 50% when compared with petroleum jelly (Vaseline). However, there is no difference in patient satisfaction (95660). Additionally, a larger clinical trial in patients with breast cancer shows that applying a sodium pentaborate pentahydrate 3% gel to radiation sites 15 minutes before each session for 25 sessions reduces the risk of dermatitis by 90%, erythema by 87%, dry desquamation by 92%, and moist desquamation by 97% when compared with a placebo gel (109557).
• Vaginal candidiasis. Boric acid applied intravaginally seems to reduce vaginal candidiasis. Details: Some limited clinical research shows that applying boric acid powder intravaginally 600 mg once or twice daily for up to 3 weeks can treat candidiasis and other vaginal fungal infections, including resistant and chronic infections (15443,15444,15446,15449,15450,15451,15453); however, this research is limited by low study quality. For Candida glabrata yeast infections, which are less prevalent than Candida albicans infections, some evidence shows that intravaginal boric acid capsules are effective in about 65% to 70% of azole-resistant infections; however, boric acid capsules appear to be less effective than intravaginal flucytosine (Ancobon) (15445,15454). For Candida krusei infections, which are rare and resistant to azole antifungal treatment, boric acid capsules also appear to be effective in some cases (15448).

POSSIBLY INEFFECTIVE

• Athletic performance. Oral boron does not seem to improve athletic performance. Details: A small clinical study in male bodybuilders shows that taking boron 2.5 mg daily for 7 weeks does not increase lean body mass, muscle mass, or testosterone levels when compared with placebo (944). Furthermore, the International Society of Sports Nutrition (ISSN) does not recommend boron supplementation as a nutritional ergogenic aid due to a lack of supportive evidence (101009).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral boron is beneficial for age-related cognitive decline. Details: Two very small clinical studies in healthy older adults show that taking boron 3.25 mg daily for up to 49 days orally might improve cognitive function and fine motor skills when compared with lower amounts of boron (943).
• Diabetic foot ulcers. It is unclear if topical boron is beneficial for use in diabetic foot ulcers. Details: A large clinical study in adults with diabetic foot ulcers shows that applying boron (sodium pentaborate 3%) gel twice daily for 1 month marginally reduces ulcer severity, measured by the Wagner Classification system at 25 days and 2 months, when compared with control; recurrence and infection rate were also modestly reduced at 2 months (112423). However, it is unclear whether the analysis controlled for systemic antibiotic use among the two groups, which effects the validity of these findings.
• Dysmenorrhea. It is unclear if oral boron is beneficial for reducing pain during menstruation. Details: A small clinical study in young females with moderate to severe dysmenorrhea suggests that taking boron tetraborate 10 mg daily, starting two days before and continuing until three days after the start of menstruation for two menstrual cycles, reduces pain levels by 24% and pain duration by 1.5 hours, or 34%. Both pain and pain duration were decreased by only 9% in patients receiving placebo (95428).
• Kidney stones (nephrolithiasis). It is unclear if boron is beneficial for medical expulsive therapy after extracorporeal shockwave lithotripsy. Details: A large clinical study in adults undergoing extracorporeal shockwave lithotripsy for kidney stones conducted in Iran shows that taking boron 10 mg twice daily for 2 weeks does not statistically improve the rate of stone expulsion when compared with tamsulosin; however, boron may have fewer side effects (i.e., orthostatic hypotension, headache, nausea, erectile dysfunction) (112414).
• Kidney transplant. It is unclear if oral boron is beneficial in patients receiving a kidney transplant. Details: Observational research in kidney transplant recipients has found that higher boron intake, as measured by urinary boron levels, is associated with a lower risk of mortality when compared with lower intake. Patients with 24-hour urinary boron levels in the top tertile had a 49% lower risk of all-cause mortality when compared with those in the lowest tertile; however, there was no association with graft failure (109556). It is unclear if these findings can be generalized to boron supplements.
• Obesity. Although there has been interest in using oral boron for obesity, there is insufficient reliable information about the clinical effects of boron for this purpose.
• Osteoarthritis. It is unclear if oral boron is beneficial for osteoarthritis symptoms. Details: Small low quality studies in patients with osteoarthritis suggest that taking boron tetraborate 3-6 mg daily for up to 8 weeks might improve pain and other symptoms when compared with a lower intake of boron (941,36870).
• Osteoporosis. It is unclear if oral boron is beneficial for osteoporosis. Details: Preliminary clinical research in postmenopausal adults shows that taking boron 3 mg daily does not improve bone density when compared with placebo (36872).
• Periodontitis. Small clinical studies suggest that adding topical boric acid to scaling and root planing treatment may be beneficial in periodontitis. Details: A meta-analysis of four small clinical studies in 117 patients with periodontitis shows that using boric acid 0.75% gel or solution in addition to scaling and root planing seems to slightly improve probing pocket depth (PPD) and clinical attachment level (CAL) when compared with placebo or saline control (105690). Another small clinical study in patients with periodontitis shows that using boric acid 0.5% for irrigation in addition to scaling and root planing seems to improve CAL and PPD to a similar degree as using povidone-iodine 0.1% (105691). The available research was conducted in Turkey, Vietnam, and India; it is unknown if these findings are generalizable to other geographic locations.
• Tooth extraction. It is unclear if boron is beneficial for use in periodontal healing after impacted third molar surgery. Details: A moderate-sized clinical study in adults 18 to 40 years old shows that using boron 0.1% to 2.5% and chlorhexidine 0.12% mouthwash for 7 days after impacted third molar surgery marginally improves swelling and self-reported pain on day 7, and the higher boron concentrations also improve pain at day 4 when compared with chlorhexidine alone, but does not improve the number of analgesics used or periodontal scores (112379). However, the validity of these results is limited by a lack of statistical adjustment for multiple comparisons which can lead studies to show differences between treatment groups in error (i.e., false positive findings). Additionally, the study period coincides with the expected recovery time (i.e., 2-7 days), making it unclear if any effects are due to the intervention or control. More evidence is needed to rate boron for these uses.

(Read more about BORON)

POSSIBLY EFFECTIVE

• Diabetes. Oral prickly pear cactus might help reduce postprandial blood glucose in patients with diabetes. Details: Some preliminary clinical research shows that prickly pear cactus decreases blood glucose levels in patients with type 2 diabetes. Single doses can decrease blood glucose levels by 17% to 48% in some patients (14807,65322,65326). For example, one small clinical study in adults with diabetes shows that adding prickly pear cactus to breakfast meals decreases postprandial glucose when compared with the equicaloric breakfast meals without prickly pear cactus (14807). However, it is not known if long-term use consistently lowers blood glucose levels and decreases glycated hemoglobin (HbA1c) levels.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral prickly pear cactus prevents age-related cognitive decline in older adults. Details: A small clinical study in healthy adults 55 years and older living in Korea shows that taking ethanolic prickly pear pad extract 960 mg (containing about 0.5 mg dihydrokaempferol) daily for 12 weeks does not affect performance on cognitive tests when compared with placebo. However, in a subgroup of patients 70 years or younger, there was a small improvement on certain cognitive tests when compared with placebo (105903).
• Benign prostatic hyperplasia (BPH). It is unclear if oral prickly pear cactus is beneficial in patients with BPH. Details: Preliminary clinical research shows that some patients with BPH who take powdered prickly pear cactus flowers 500 mg three times daily for 2-8 months have subjective improvements in symptoms such as urgency and feelings of fullness in the bladder (12175).
• Familial hypercholesterolemia. It is unclear if oral prickly pear cactus is beneficial in patients with BPH. Details: One very small clinical study in patients with familial hypercholesterolemia shows that consuming prickly pear cactus pulp 250 grams daily for 4 weeks, in combination with dietary intervention, reduces total cholesterol by 30 mg/dL and low-density lipoprotein (LDL) cholesterol by 34 mg/dL when compared to baseline. However, taking prickly pear cactus does not improve high-density lipoprotein (HDL) cholesterol or triglyceride levels in these patients (65274). The validity of this finding is limited by the lack of a comparator group.
• Dyspepsia. Oral prickly pear cactus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in healthy adults shows that taking a specific combination product containing prickly pear cactus and olive extract (Mucosave, Bionap S.R.L.) 400 mg daily for 8 weeks seems to improve dyspepsia and other gastrointestinal symptoms when compared with placebo (105904). It is unclear if the benefit is from prickly pear cactus, olive, or the combination. It is also unclear if this benefit would occur in patients with clinically diagnosed dyspepsia.
• Hangover. It is unclear if oral prickly pear cactus is beneficial in patients with hangover. Details: A small clinical study in healthy adults shows that taking 1600 IU of a specific prickly pear cactus fruit extract (Tex-OE, Extracts Plus Inc.) as a single dose 5 hours prior to binge alcohol consumption does not reduce overall hangover symptoms when compared with placebo. However, it may help to reduce specific symptoms such as nausea, anorexia, and dry mouth when compared with placebo. Furthermore, there was a 62% lower odds of severe hangover in the prickly pear cactus group when compared with placebo (12085).
• Hypercholesterolemia. It is unclear if oral prickly pear cactus lowers cholesterol levels. Details: A small clinical study in patients with primary isolated hypercholesterolemia or combined hyperlipidemia shows that, when used in combination with a Step 1 diet, taking prickly pear cactus pulp 250 grams daily can reduce total cholesterol by 12%, low-density lipoprotein (LDL) cholesterol by 15%, and triglycerides by 12%; however, levels of high-density lipoprotein (HDL) cholesterol do not seem to be affected (65263). It is unclear how these results compare to the control group.
• Metabolic syndrome. It is unclear if oral prickly pear cactus is beneficial in patients with metabolic syndrome. Details: One small clinical study in females with metabolic syndrome shows that taking a specific dehydrated prickly pear cactus pad product (NeOpuntia, Bio Serae) 4.8 grams in 3 divided doses daily for 6 weeks does not affect blood lipid levels when compared with placebo (65293). Another small study in adults with 1-2 risk factors for metabolic syndrome shows that consuming durum wheat pasta 500 mg, containing prickly pear cactus pad extract 3%, weekly for 1 month modestly reduces waist circumference, blood glucose, and triglycerides, but not other lipid parameters or weight, when compared with baseline (105902). The validity of these findings is limited by the lack of a comparator group.
• Obesity. It is unclear if oral prickly pear cactus is beneficial for weight loss. Details: A meta-analysis of 4 clinical trials shows that taking prickly pear cactus orally for 8 weeks to 2 years does not improve weight loss when compared with placebo. However, the results of this analysis are limited by the low methodological quality and small sample sizes of many of the included studies (92146). Studies in the meta-analysis used prickly pear cactus pads 3-15 grams daily for up to 2 years or prickly pear cactus fruit skin extract 400 mg daily for 16 weeks. Specific prickly pear cactus pad products included NeOpuntia (Bio Serae) 4.8 grams daily and Litramine (InQpharm North America LLC) 3 grams daily (92146). More evidence is needed to rate prickly pear cactus for these uses.

(Read more about PRICKLY PEAR CACTUS)

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)

LIKELY SAFE ...when used orally and appropriately. Boron is safe in amounts that do not exceed the tolerable upper intake level (UL) 20 mg daily (7135). ...when used vaginally. Boric acid, the most common form of boron, has been safely used for up to six months (15443,15444,15445,15446,15458,15449,15451,15453,15454). ...when used topically. Boron, in the form of sodium pentaborate pentahydrate 3% gel, has been applied to the skin with apparent safety up to four times daily for up to 5 weeks (95660,109557).

POSSIBLY UNSAFE ...when used orally in doses exceeding the UL of 20 mg daily. Higher doses might adversely affect the testes and male fertility (7135). Poisoning has occurred after ingestion of boron 2.12 grams daily for 3-4 weeks (17). Death has occurred after ingesting a single dose of 30 grams (36848,36863).

CHILDREN: LIKELY SAFE
when used orally and appropriately. Boron is safe in amounts that do not exceed the tolerable upper intake level (UL). The UL by age is 3 mg daily at 1-3 years, 6 mg daily at 4-8 years, 11 mg daily at 9-13 years, and 17 mg daily at 14 years or older (7135). The UL for infants has not been determined (7135).

CHILDREN: POSSIBLY UNSAFE
when used orally in doses exceeding the age-based UL (7135). ...when applied topically in large quantities. Infant deaths have occurred after the use of topical boric acid powder to prevent diaper rash (36873,36874).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Boron is safe in amounts that do not exceed the UL during pregnancy or lactation, which is 20 mg daily in those 19-50 years of age or 17 mg daily for those 14-18 years of age (7135).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in doses exceeding the UL. Higher doses might impair growth and cause adverse effects in the developing fetus (7135,102058). ...when used vaginally. Intravaginal boric acid has been associated with a 2.7- to 2.8-fold increased risk of birth defects when used during the first 4 months of pregnancy (15443,15645).

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LIKELY SAFE ...when prickly pear cactus fruit and pads are used orally as a food (5969).

POSSIBLY SAFE ...when prickly pear cactus fruit and pads are used orally and appropriately in supplemental amounts, short-term. Prickly pear cactus fruit pulp 250 grams twice daily has been used with apparent safety for up to 2 weeks (12086) and prickly pear cactus pads 3-15 grams daily have been used with apparent safety for up to 2 years (92146). Extracts of prickly pear fruit skin 400 mg daily or prickly pear pads 960 mg daily have been used with apparent safety for 12-16 weeks (92146,105903).

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

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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).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Combining prickly pear cactus with antidiabetes drugs might increase the risk of hypoglycemia.  Details Case reports show that combining prickly pear cactus with antidiabetes drugs such as chlorpropamide, glyburide, glipizide, and metformin can increase the risk of hypoglycemia in patients with type 2 diabetes (5968,14806,17226,65319,92146). Advise patients to monitor glucose levels closely. Dose adjustments may be necessary.

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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.

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General ...Orally, boron is generally well tolerated when used in doses below the tolerable upper intake level (UL) of 20 mg. Vaginally, boron is well tolerated.
Most Common Adverse Effects:
Orally: Anorexia, dermatitis, erythema, indigestion.
Vaginally: Burning and pain.

Dermatologic ...Orally, chronic use of 1 gram daily of boric acid or 25 grams daily of boric tartrate can cause dermatitis and alopecia (7135).
Larger doses can result in acute poisoning. Symptoms of poisoning in adults and children may include skin erythema, desquamation, and exfoliation (17).

Gastrointestinal ...Orally, chronic use of 1 gram daily of boric acid or 25 grams daily of boric tartrate can cause anorexia and indigestion (7135).
Larger doses can result in acute poisoning. Children who have ingested 5 grams or more of borates can have persistent nausea, vomiting, and diarrhea leading to acute dehydration, shock, and coma. Adults who have ingested 15-20 grams of borate can exhibit nausea, vomiting, diarrhea, epigastric pain, hematemesis, and a blue-green discoloration of feces and vomit (17).

Genitourinary ...Vaginally, boric acid can cause vulvovaginal burning and dyspareunia in males if intercourse occurs shortly after vaginal treatment (15447).

Neurologic/CNS ...Orally, large doses can result in acute poisoning. Poisoning with boron can cause hyperexcitability, irritability, tremors, convulsions, weakness, lethargy, and headaches (17).

Ocular/Otic ...Exposure to boric acid or boron oxide dust has been reported to cause eye irritation (36852).

Pulmonary/Respiratory ...Exposure to boric acid and boron oxide dust has been reported to cause mouth and nasal passage irritation, sore throat, and productive cough (36852).

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General ...Orally, prickly pear cactus is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal fullness, dyspepsia, mild diarrhea, nausea.

Dermatologic ...Orally, prickly pear cactus has been linked to rare cases of urticaria and pruritus. In a clinical study of 41 patients taking prickly pear cactus pad ethanolic extract, three patients experienced pruritus and one patient experienced urticaria (105903).

Gastrointestinal ...Orally, prickly pear cactus may cause mild diarrhea, dyspepsia, nausea, increased stool volume and frequency, and abdominal fullness (7028,65266,105903). Cases of low colonic obstruction and rectal phytobezoars resulting in rectal perforation have been reported for patients who ingested prickly pear cactus fruit seeds (65260,65266). However, these events are extremely rare and attributed to the ingestion of a large number of fruits. Because dried prickly pear cactus swells into a mass much larger than its original size, it may potentially cause dangerous blockages of the esophagus or intestines. Similar products have been associated with serious or even fatal blockages, but cases of such blockages from prickly pear cactus are lacking in the scientific literature.

Neurologic/CNS ...Orally, prickly pear cactus has been linked to rare cases of headache, insomnia, and dizziness (65266,105903). In a clinical study of 41 patients taking prickly pear cactus pad ethanolic extract, two patients experienced headache, one patient experienced dizziness, and one patient experienced insomnia (105903).

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