Saw Palmetto Combination #1 by Genestra Brands

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. Although there has been interest in using oral alfalfa for diabetes, there is insufficient reliable information about the clinical effects of alfalfa for this purpose.
• Dyspepsia. Although there has been interest in using oral alfalfa for dyspepsia, there is insufficient reliable information about the clinical effects of alfalfa for this purpose.
• Hypercholesterolemia. It is unclear if oral alfalfa seeds are beneficial in patients with hypercholesterolemia. Details: A small, uncontrolled clinical study in patients with hypercholesterolemia shows that taking heat-prepared alfalfa seeds 40 grams three times daily for 8 weeks reduces total cholesterol and low-density lipoprotein (LDL) cholesterol levels when compared to baseline (5816). The validity of these findings is limited by the lack of a control group.
• Menopausal symptoms. Although there has been interest in using oral alfalfa for menopausal symptoms, there is insufficient reliable information about the clinical effects of alfalfa for this purpose. There is insufficient reliable information available about the effectiveness of alfalfa for its other uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. Although there has been interest in using oral American spikenard for asthma, there is insufficient reliable information about the clinical effects of American spikenard for this purpose.
• Common cold. Although there has been interest in using oral American spikenard for the common cold, there is insufficient reliable information about the clinical effects of American spikenard for this purpose. More evidence is needed to rate American spikenard for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Topical calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with mild to moderate acne associated with mask wearing shows that topical application of a combination of calendula 4%, licorice root extract 0.3%, and snail secretion filtrate 40% (AI complex) to the face twice daily for 12 weeks modestly reduces inflammatory, but not non-inflammatory or total, acne lesions when compared with placebo. There was no difference in overall treatment success, defined as at least almost clear skin or a large improvement (110322). It is unclear if any benefits are due to calendula, other ingredients, or the combination.
• Bacterial vaginosis. It is unclear if topical calendula is beneficial for improving bacterial vaginosis. Details: A small clinical study in patients with bacterial vaginosis shows that applying 5 grams of vaginal cream containing calendula flower extract before bed for one week improves vaginal burning, odor, painful urination, and painful intercourse when compared to baseline (96649). The validity of these findings is limited by the lack of a comparator group.
• Burns. It is unclear if oral calendula is beneficial for burn healing. Details: A small clinical trial in patients hospitalized for second-degree burns shows that taking calendula 2 grams daily for 2 weeks has a large beneficial effect on wound healing when compared with placebo (110323).
• Chronic obstructive pulmonary disease (COPD). Oral calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in males aged 40-70 years with a history of smoking and stage 2 COPD shows that taking a specific combination of calendula flowers 165 mg, elderberry 165 mg, and heart's ease herb 165 mg (Inflaminat, INAT-Farma), 3 capsules daily for 6 months, modestly improves symptoms, as measured on the breathlessness, cough, and sputum scale (BCSS), and mean forced expiratory volume in 1 second (FEV1) when compared to baseline. However, there was no improvement of COPD exacerbations or other pulmonary function tests (103629). The validity of this finding is limited by the lack of statistical comparison to the placebo group. Furthermore, it is unclear if these effects are due to calendula, the other ingredients, or the combination.
• Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). Calendula in rectal suppositories has only been evaluated in combination with turmeric extract; its effect when used alone is unclear. Details: A small clinical study in patients with CP/CPPS shows that using a rectal suppository containing turmeric extract 350 mg and calendula extract 80 mg daily for one month improves pain, peak urine flow rate, and erectile function when compared with placebo (96648). It is unclear if these effects are due to calendula, turmeric, or the combination.
• Conjunctivitis. Although there is interest in using topical calendula for conjunctivitis, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Diabetic foot ulcers. It is unclear if topical calendula is beneficial for improving diabetic foot ulcers. Details: Observational research has found that applying a calendula hydroglycolic extract spray in addition to standard care and hygiene is associated with reduced bacterial colonization and improved odor in patients that have had a diabetic ulcer for over 3 months (93548).
• Diaper rash. It is unclear if topical calendula is beneficial for improving diaper rash. Details: One preliminary clinical study in children less than 3 years of age shows that topical application of calendula 1.5% ointment three times daily for 10 days improves diaper rash when compared with aloe gel (19779). However, other preliminary clinical research shows that applying calendula 1.5% cream every 4-6 hours for 3 days improves diaper rash in fewer infants when compared to treatment with bentonite 50% mineral solution (93545,93554).
• Dysmenorrhea. Although there is interest in using oral calendula for dysmenorrhea, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Gingivitis. It is unclear if using a mouth rinse with calendula is beneficial for improving gingivitis. Details: Preliminary clinical research in patients with mild gingivitis and bleeding gums shows that rinsing the mouth with a tincture containing calendula 25% (Dr. Willmar Schwabe Germany Home Pharmacy Pvt. Ltd.) twice daily for 6 months decreases plaque, gingivitis, and bleeding by 10% to 18% when compared to rinsing with water (93551). Other preliminary clinical research in adults with mild to moderate gingivitis and mild plaque shows that rinsing the mouth with a combination mouthwash containing a 5% extract of calendula, rosemary, and ginger for 30 seconds twice daily after food for 2 weeks decreases plaque, gingivitis, and bleeding when compared with a placebo mouthwash. The effects of this combination mouthwash appear to be similar to chlorhexidine 0.2% mouthwash (93555). It is unclear if these effects are due to calendula, other ingredients, or the combination.
• Hemorrhoids. Although there is interest in using topical calendula for hemorrhoids, there is insufficient reliable information about the clinical effects of calendula for this purpose.
• Liver disease. Although there is interest in using oral calendula for liver disease, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Mosquito repellent. It is unclear if topical calendula essential oil helps to repel mosquitos. Details: Preliminary clinical research shows that applying calendula 50% essential oil to the skin does not repel mosquitos as effectively as applying DEET. Mean repellency time was about 2 hours for patients applying calendula, which was shorter than the 6 hour repellency with DEET (93562).
• Oral leukoplakia. It is unclear if topical calendula is beneficial for improving oral leukoplakia. Details: Preliminary clinical research in patients with oral leukoplakia shows that applying a gel containing calendula flower extract 0.2% three times daily for one month reduces lesion size by about 2 cm when compared to baseline (96650). The validity of this finding is limited by the lack of a comparator group.
• Oral mucositis. Calendula as a mouth rinse has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with head and neck cancer receiving chemotherapy and radiotherapy shows that rinsing with 7 mL of a specific product (Faringel, Cadigroup) containing calendula powder extract 2%, propolis, aloe vera, and chamomile three times daily for 6 weeks does not prevent oral mucositis when compared with placebo (95879).
• Otitis media. Topical calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children with otitis media shows that applying a specific combination product containing calendula, mullein, garlic, and St. John's wort in olive oil (Otikon Otic Solution, Healthy-On Ltd, Petach-Tikva, Israel), five drops into the affected ear three times daily for 3 days, may reduce ear pain when compared with baseline (39500,39552). It is unclear if this effect is due to calendula, other ingredients, or the combination. Furthermore, due to the lack of an adequate control group, it is unclear whether the pain reduction was due to the resolution of otitis media.
• Peptic ulcers. Although there is interest in using oral calendula for peptic ulcers, there is insufficient reliable information about the clinical effects of calendula for this condition.
• Pressure ulcers. It is unclear if topical calendula is beneficial for improving pressure ulcers. Details: Observational research has found that the application of a specific calendula product (Plenusdermax) twice daily is associated with improved healing in patients with pressure ulcers that have not changed in size for at least 3 months (93549). Preliminary clinical research in hospice patients with symptomatic pressure ulcers and other wounds shows that applying a homeopathic powder (RGN107) containing calendula 0.1% and arnica 0.01% to wounds for 4 weeks is rated by the patients and caregivers to be acceptable for controlling pain, odor, and exudate when compared with baseline (96647). The validity of this finding is limited by the lack of a control group.
• Radiation dermatitis. It is unclear if topical calendula reduces radiation dermatitis symptoms. Details: A meta-analysis of three preliminary clinical trials in patients with breast cancer shows that topical calendula does not affect the development of radiation dermatitis or the incidence of moderate to severe symptoms when compared to control (110325). In addition, a meta-analysis of two studies (39503,93560) shows that topical calendula does not reduce the incidence of treatment interruptions due to severe symptoms of radiation dermatitis (110325). In one of the included studies, a specific calendula petroleum jelly ointment (Pommade au Calendula par Digestion, Boiron Ltd.) used twice daily during radiation therapy was found to reduce acute radiation dermatitis occurrence when compared with topical trolamine (Biafine) (39503). However, it is unclear if the benefit was due to calendula or petroleum jelly. Another clinical study used a specific calendula 10% cream in wool fat and sesame oil (Calendula Weleda, Weleda AG) twice daily during radiation therapy. This product was found to be no better than aqueous petroleum jelly cream (Essex, Schering-Plough) for reducing acute skin reactions and dermatitis symptoms of pain, burning, itching, pulling, and tenderness (93560).
• Vaginal atrophy. Topical calendula has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in menopausal patients with vaginal atrophy shows that use of a specific vaginal gel containing calendula, Lactobacillus sporogenes, isoflavones, and lactic acid (Estromineral Gel, Rottapharm-Madaus) daily for 4 weeks reduces vaginal itching, burning, dryness, and painful intercourse when compared with no topical treatment. Both groups also received oral isoflavones (39534). It is unclear if these effects are due to calendula, other ingredients, or the combination.
• Vaginal candidiasis. One small clinical study suggest that topical calendula is not beneficial for the treatment of vaginal candidiasis. Details: Preliminary clinical research shows that applying 5 grams of calendula 1% cream intravaginally once daily for 7 days effectively treats vaginal candidiasis in 34% fewer patients when compared with using clotrimazole 1% cream (93559).
• Venous leg ulcers. It is unclear if topical calendula is beneficial for improving venous leg ulcers. Details: Preliminary clinical research shows that applying a calendula 7.5% ointment twice daily for 3 weeks to venous leg ulcers accelerates healing when compared with applying saline solution dressing (39509).
• Wound healing. It is unclear if topical calendula is beneficial for improving the healing of small wounds. Details: Two small clinical trials in postpartum patients show that applying calendula ointment (formulation unspecified) to the episiotomy wound every 8 hours for 5-10 days modestly reduces pain, and seems to speed up the resolution of redness, edema, and ecchymosis, when compared with standard care, such as application of betadine solution (93550,105087). Another small clinical study in adults with wounds smaller than 10 cm² on the hands and fingers shows that applying calendula flower extract 2% to the wound twice daily may modestly improve healing and epithelialization time when compared with mineral oil (107806). More evidence is needed to rate calendula for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. Although there has been interest in using oral damiana for asthma, there is insufficient reliable information about the clinical effects of damiana for this purpose.
• Cognitive function. Although there has been interest in using oral damiana for cognitive function, there is insufficient reliable information about the clinical effects of damiana for this purpose.
• Constipation. Although there has been interest in using oral damiana for constipation, there is insufficient reliable information about the clinical effects of damiana for this purpose.
• Depression. Although there has been interest in using oral damiana for depression, there is insufficient reliable information about the clinical effects of damiana for this purpose.
• Diabetes. Although there has been interest in using oral damiana for diabetes, there is insufficient reliable information about the clinical effects of damiana for this purpose.
• Dyspepsia. Although there has been interest in using oral damiana for dyspepsia, there is insufficient reliable information about the clinical effects of damiana for this purpose.
• Headache. Although there has been interest in using oral damiana for headache, there is insufficient reliable information about the clinical effects of damiana for this purpose.
• Menopausal symptoms. Although there has been interest in using oral damiana for menopausal symptoms, there is insufficient reliable information about the clinical effects of damiana for this purpose.
• Obesity. Oral damiana has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in overweight adults shows that taking a combination product containing damiana 36 mg, guarana 95 mg, and yerba mate 112 mg, orally three times daily for 45 days increases weight loss when compared with placebo (11866). It is unclear if this effect is due to damiana, other ingredients, or the combination.
• Nocturnal enuresis. Although there has been interest in using oral damiana for nocturnal enuresis, there is insufficient reliable information about the clinical effects of damiana for this purpose.
• Sexual dysfunction. Oral damiana has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific combination product containing damiana, L-arginine, Panax ginseng, ginkgo, vitamins, and minerals (ArginMax for Women, Daily Wellness Co.) improves sexual satisfaction and desire, increases orgasm frequency, and reduces vaginal dryness when compared with placebo in females interested in improving their sexual function (46933). It is unclear if this effect is due to damiana, other ingredients, or the combination. More evidence is needed to rate damiana for these uses.

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POSSIBLY EFFECTIVE

• Genital herpes. Oral eleuthero root extract might help to prevent and reduce the severity of genital herpes outbreaks. Details: One clinical study in patients with recurrent genital herpes infections shows that taking a specific eleuthero root extract (Elagen) 400 mg, standardized to contain eleutheroside 0.3%, daily for at least 3 months reduces the frequency, severity, and duration of outbreaks when compared with placebo (730).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. Small clinical studies suggest that oral eleuthero root is not beneficial for improving athletic performance. Details: One study in trained distance runners shows that a specific eleuthero root liquid extract, standardized to eleutherosides B and E content, taken as 3.4 mL daily for 6 weeks, does not affect endurance, performance, or psychological, cardiac, or respiratory parameters when compared with placebo (7522). Small studies in trained athletes or healthy adults show that taking eleuthero 800-1200 mg daily (Endurox) for 1-6 weeks does not seem to have any effect on cycling performance time, respiration, lactate production, or heart rate recovery during cycling, stair-stepping exercise, treadmill, or cyclic ergometry when compared with placebo (2335,7600,7601,8994). However, there has been some speculation that a longer duration of supplementation is needed for benefit. One study in recreationally trained athletes shows that taking a specific powdered eleuthero root product 400 mg twice daily for 8 weeks increased cycling endurance time by 23% and maximal oxygen consumption by 12% when compared with placebo. This product was standardized to contain eleutheroside B 0.11% and eleutheroside E 0.12% (17186).
• Bipolar disorder. It is unclear if oral eleuthero root is beneficial for bipolar disorder. Details: A small clinical study in Chinese adolescents ages 12-17 years with bipolar disorder shows that taking eleuthero root 750 mg orally three times daily, in conjunction with lithium for 6 weeks, induces similar response rates and remission rates when compared with lithium plus fluoxetine 20 mg (75028). It is not clear how this response rate compares to the use of lithium alone.
• Cardiovascular disease (CVD). It is unclear if oral eleuthero fruit is beneficial for preventing the development of CVD. Details: One small clinical study in healthy adults with at least two cardiovascular risk factors shows that taking an aqueous extract of eleuthero fruit 500 mg daily for 12 weeks seems to modestly reduce systolic blood pressure and arterial stiffness, as measured by brachial-ankle pulse wave velocity, when compared with placebo. It did not affect diastolic blood pressure, flow-mediated dilation, or carotid intima-media thickness. Also, taking a higher 1000 mg dose of the same eleuthero extract daily did not have significant effects on any measured parameters (105025).
• Chronic fatigue syndrome (CFS). It is unclear if oral eleuthero root is beneficial for CFS. Details: One clinical study in adults with CFS shows that taking eleuthero root extract 2 grams daily for 2 months improves fatigue severity and duration when compared with baseline, but not when compared with placebo (11099).
• Cognitive function. It is unclear if oral eleuthero is beneficial for cognitive function. Details: A very small clinical study in middle-aged people shows that taking eleuthero 325 mg twice daily might improve selective memory when compared with placebo (2574). Another very small study in healthy adults shows that taking a combination product containing extracts of eleuthero leaf 203 mg and Drynaria fortunei 20 mg daily for 12 weeks improves figure recall, but not immediate memory or attention, when compared with placebo (102316). It is unclear if this effect is due to eleuthero, Drynaria fortunei, or the combination.
• Common cold. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some clinical research shows that taking capsules of a specific combination product containing eleuthero plus andrographis (Kan Jang, Swedish Herbal Institute) orally improves symptoms of the common cold when started within 72 hours of symptom onset. Some symptoms can improve after 2 days of treatment; however, it typically takes 4-5 days of treatment for maximal symptom relief (5784,10795,12380). Some research shows the combination of eleuthero and andrographis relieves cold symptoms better than echinacea or placebo in children (12381). It is unclear if this effect is due to eleuthero, andrographis, or the combination.
• Diabetes. It is unclear if oral eleuthero is beneficial for improving glycemic control in type 2 diabetes. Details: One small clinical study in adults with type 2 diabetes shows that taking a specific eleuthero extract, standardized to contain eleutherosides E and B 1.12%, as 480 mg daily for 3 months, decreases fasting glucose by a mean of 36 mg/dL, postprandial blood glucose by a mean of 35 mg/dL, glycated hemoglobin (HbA1c) by a mean of 0.8%, triglycerides by a mean of 106 mg/dL, and total cholesterol by a mean of 21 mg/dL when compared with placebo (91509).
• Diabetic neuropathy. It is unclear if oral eleuthero is beneficial for diabetic neuropathy. Details: One small clinical study in adults with type 2 diabetes shows that taking a specific eleuthero extract, standardized to contain eleutherosides E and B 1.12%, as 480 mg daily for 3 months, modestly improves subjective symptoms of diabetic neuropathy when compared with placebo (91509).
• Familial Mediterranean fever. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children ages 3-15 years with familial Mediterranean fever shows that taking a specific combination product (ImmunoGuard, Inspired Nutritionals) containing eleuthero, andrographis, schisandra, and licorice for one month reduces the duration, frequency, and severity of disease recurrence when compared with placebo (12382). It is unclear if this effect is due to eleuthero, other ingredients, or the combination.
• Fibromyalgia. Although there is interest in using oral eleuthero for fibromyalgia, there is insufficient reliable information about the clinical effects of eleuthero for this condition.
• Hangover. It is unclear if oral eleuthero root is beneficial for hangovers. Details: One small clinical study in healthy males shows that consuming one bottle of a powdered polysaccharide-rich extract of eleuthero root before and after consuming alcohol modestly reduces the severity of hangover as measured by the Acute Hangover Scale questionnaire score when compared with placebo (91508). However, the validity of these findings is brought into question due to the incomplete study information provided.
• Influenza. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with influenza shows that taking a specific combination product containing eleuthero 20-30 mg plus andrographis 178-266 mg (Kan Jang, Swedish Herbal Institute) three times daily for 3-5 days relieves symptoms more quickly than amantadine. This combination product also reduced the risk of post-influenza complications, such as sinusitis or bronchitis, when compared with amantadine (10441). It is unclear if these effects are due to eleuthero, andrographis, or the combination.
• Osteoarthritis. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking two capsules each containing 400 mg of a combination of eleuthero, Panax pseudoginseng, and rehmannia daily for 6 weeks improves physical function in individuals with knee osteoarthritis when compared with placebo. However, the combination does not seem to reduce pain or stiffness when compared with placebo (74950). It is unclear if this effect is due to eleuthero, other ingredients, or the combination.
• Osteoporosis. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in postmenopausal patients shows that taking low-dose calcium and vitamin D3 in combination with a 250 mg blend of rehmannia root and eleuthero stem bark extracts twice daily for 12 months attenuates the loss of spine and femur bone mineral density when compared with placebo or high-dose calcium and vitamin D (75036). It is unclear if this effect is due to eleuthero, rehmannia, or the combination.
• Pneumonia. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with acute, nonspecific pneumonia shows that taking a specific combination product (ADAPT-232), containing eleuthero, rhodiola, and schisandra, as 20 mL twice daily for 10-15 days in conjunction with conventional treatment, reduces the duration of antibiotic treatment and improves quality of life when compared with conventional treatment alone (71152).
• Quality of life. It is unclear if oral eleuthero root improves quality of life in older healthy adults. Details: A small clinical study in elderly volunteers shows that taking eleuthero 300 mg daily improves social functioning and mental well-being after 4 weeks of treatment when compared with placebo. However, this improvement was not maintained after 8 weeks of treatment (15586).
• Rheumatoid arthritis (RA). Although there is interest in using oral eleuthero for RA, there is insufficient reliable information about the clinical effects of eleuthero for this condition.
• Stress. It is unclear if oral eleuthero root is beneficial for stress. Details: One clinical study in adults 30-50 years of age with symptoms of stress shows that taking a specific eleuthero root extract (WS 1070) 120 mg daily for 8 weeks does not improve fatigue, exhaustion, cognitive alertness, or measures of stress when taken alone or in conjunction with stress management training (91510). However, another small clinical study in healthy females 20-68 years of age who have experienced stress for a prolonged period of time shows that taking a single, 270 mg dose of a combination agent (ADAPT-232) containing eleuthero, rhodiola, and schisandra improves attention and cognitive speed and accuracy when compared with placebo (19289). It is unclear if these effects are due to eleuthero, other ingredients, or the combination.
• Upper respiratory tract infection (URTI). Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with an uncomplicated URTI shows that taking 30 mL of a combination product (Kan Jang, Swedish Herbal Institute) containing extracts of eleuthero root (eleutherosides B and E 0.03 mg/mL), echinacea root, and malabar nut leaf daily does not reduce the severity or frequency of cough by a clinically meaningful amount after 3-4 days of treatment when compared with bromhexine hydrochloride or placebo (95648). However, a non-blinded clinical study shows that taking 30 mL of this same product three times daily for 6 days improves the severity and frequency of coughing and the degree of nasal congestion when compared with bromohexine. Additionally, patients taking the combination product recovered two days sooner, on average, than those taking bromohexine (48569). The reason for these conflicting findings is unclear but may be due to an inadequate duration of treatment in the first study and/or lack of blinding in the second study. Also, it is unclear if any benefit is due to eleuthero, other ingredients, or the combination. Other research has evaluated a capsule formulation of Kan Jang (Swedish Herbal Institute), with each capsule containing eleuthero root 11.4 mg and andrographis 195 mg. One small clinical study in patients with an uncomplicated URTI shows that taking this product as two capsules three times daily for 5 days reduces the median number of sick leave days to 2 days, compared with 3 days in the placebo group. It also increases the total number of recovered patients on day 3 to 75%, compared with 55% of those taking placebo (107471). More evidence is needed to rate eleuthero for these uses.

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POSSIBLY EFFECTIVE

• Transurethral resection of the prostate (TURP). Saw palmetto 320 mg daily seems to improve outcomes after TURP surgery in a dose-dependent manner. Details: Clinical research shows that taking saw palmetto (Permixon, Pierre Fabre Medicament) 320 mg daily for 2 months prior to TURP surgery reduces blood loss, the duration of surgery, the development of intraoperative complications, the duration of catheterization, and the length of hospitalization when compared with placebo (73323,73353). Although these studies found benefit, a small study using a lower dose of saw palmetto (Prostagood Mono, Abdi Ibrahim) 160 mg orally once daily for 5 weeks prior to TURP did not find any decrease in the risk of perioperative hemorrhage, or the density of prostate tissue (17202).

POSSIBLY INEFFECTIVE

• Benign prostatic hyperplasia (BPH). Although individual study results are conflicting, the overall body of evidence suggests that saw palmetto does not offer clinically meaningful improvements in BPH-related symptoms. Details: Research on the use of saw palmetto for improving symptoms of BPH is inconsistent and contradictory. To date, the best available evidence addressing the effectiveness of saw palmetto in patients with BPH comes from two high-quality clinical trials sponsored by the National Institutes of Health (NIH). In one of these trials, saw palmetto 160 mg twice daily for one year was ineffective for reducing moderate to severe symptoms of BPH when compared with placebo (14274). In the other trial, taking saw palmetto 320-960 mg daily for 72 weeks did not significantly improve symptoms when compared with placebo (17684). Additionally, meta-analyses of these trials and many of the small trials described below show that taking saw palmetto does not improve BPH-related signs and symptoms or International Prostate Symptom Scores (IPSS) (89441,102835). While several small, low-quality clinical trials and observational studies in patients with BPH suggest that saw palmetto provides some improvement in urinary symptoms, nocturia, urinary flow, and/or residual urine volume when compared with placebo or baseline (6750,6764,6772,73315,73383,73385,73387,89441,96570,110541), other studies show that saw palmetto has no clinically meaningful effect on BPH-related signs and symptoms, including prostate volume (5093,6752,11314,73343,96409). The validity of several of these studies is limited due to the use of per-protocol analyses and/or a lack of placebo control groups. Beyond this, reasons for these discrepant findings are unclear; however, the mixed results may be due to use of different saw palmetto products, varying study methodologies, different patient populations, and varying symptom scoring tools. Additionally, research shows significant variation in the chemical composition of commercially available saw palmetto extracts (17305,89441). Several clinical trials have compared saw palmetto to 5-alpha reductase inhibitors such as finasteride (Proscar) or dutasteride (Avodart). Some small studies suggest that it may be comparable to these medications for relieving BPH symptoms, but with less effect on prostate size or prostate-specific antigen (PSA) levels (6424,96570). It may also be better tolerated, with a positive effect on sexual dysfunction (6424,6763,18215,89441). Additionally, one observational study in patients with BPH has found that taking saw palmetto 320 mg with tamsulosin 0.4 mg daily for 6 months is associated with similar improvements in IPSS and quality of life scores, but also has a lower risk of reduced libido, when compared with tamsulosin plus dutasteride 5 mg or finasteride 0.5 mg daily (110542). Some research has also compared saw palmetto to alpha-adrenergic blockers. Alpha-adrenergic blockers appear to have a faster onset of symptom relief (2732,6750), and saw palmetto might be less effective than the alpha-adrenergic blocker prazosin (Minipress). Although some studies and a meta-analysis suggest it is similarly effective to tamsulosin (Flomax) after 6-12 months of treatment for improving various symptoms of BPH (6775,6776,11243,89441,96570,104804,107483), another meta-analysis found that alpha-blockers were more effective than saw palmetto for these outcomes (102835). Additionally, tamsulosin appears to be more effective than saw palmetto for reducing prostate volume (104802). However, some research suggests that saw palmetto may be better tolerated than tamsulosin (107483). It is unclear if taking saw palmetto with tamsulosin can improve BPH symptoms. Several low-quality studies and a meta-analysis of two of these studies show no additional benefit over using tamsulosin alone (8901,89443,89448,96410). However, one study suggests that a specific saw palmetto extract (Permixon, Pierre Fabre Medicament) 320 mg daily is associated with a 29% decrease in the IPSS when taken alone, compared with a 37% decrease when taken along with tamsulosin 0.4 mg daily for 6 months. Tamsulosin alone was associated with a 31% decrease (104802). Smaller, lower-quality studies of various combinations of saw palmetto with other ingredients have demonstrated some benefit for improving symptoms of BPH, and some have shown equivalence to finasteride, tamsulosin, or tadalafil (Cialis). These ingredients include stinging nettle root (PRO 160/120, Dr. Willmar Schwabe Pharmaceuticals) (6763,17307,73330,89441); cernitin, beta-sitosterol, and vitamin E (11241); selenium and lycopene (Profluss, Konpharma) (90354,97255); pygeum, lycopene, Epilobium parviflorum, and pumpkin seed oil (ProstateEZE Max, Caruso's Natural Health) (92164); and quercetin and beta-sitosterol (Difaprost, Difass International) (96784). Additionally, one study suggests that an enriched form of saw palmetto oil containing 3% beta-sitosterol seems to be more effective than standard saw palmetto oil containing 0.3% beta-sitosterol in reducing IPSS scores (104803).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. It is unclear if oral or topical saw palmetto is beneficial in patients with androgenic alopecia. Details: Clinical research shows that a combination of saw palmetto extract 200 mg plus beta-sitosterol 50 mg taken twice daily for 18-24 months improves subjective scores of hair quantity and quality in males with androgenic alopecia (15550). However, other clinical research shows that taking saw palmetto extract 320 mg daily for 24 months is less effective for improving hair growth in males with androgenic alopecia when compared with finasteride 1 mg daily (89444). Some clinical research shows that saw palmetto lotion applied topically twice daily for 50 weeks improves hair density by 27% in people with androgenic alopecia. However, a 13% improvement was observed in the placebo group, and no between-group comparisons were made (73435). Additionally, a small clinical study in males with androgenic alopecia receiving platelet-rich plasma every 3 weeks shows that applying 1 mL of topical saw palmetto, redensyl, and biotin daily for 12 weeks modestly improves subjective hair loss scores and photographic assessment of hair growth when compared with 1 mL of topical Procapil daily (112176). However, it is unclear if this effect is due to saw palmetto, other ingredients, or the combination.
• Asthma. Although there has been interest in using oral saw palmetto for asthma, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose.
• Chronic bronchitis. Although there has been interest in using oral saw palmetto for chronic bronchitis, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose.
• Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). It is unclear if oral saw palmetto is beneficial in patients with CP/CPPS. Details: Preliminary clinical research shows that oral saw palmetto 325 mg daily for one year does not significantly improve symptoms of CP/CPPS when compared with finasteride 5 mg once daily (11354). However, a clinical trial in patients with moderate to severe CP/CPPS shows that taking saw palmetto 160 mg orally twice daily for 12 weeks improves NIH Chronic Prostatitis Index (NIH-CPSI) score after two weeks of treatment in patients with moderate disease and after 4 weeks of treatment in patients with severe disease when compared with placebo. Independent of severity, 73% of patients taking saw palmetto report a 6-point reduction in NIH-CPSI total score, compared to 33% of patients taking placebo (107482). Saw palmetto extract has also been evaluated in combination with other ingredients. A preliminary clinical study shows that taking a combination of saw palmetto extract 320 mg, selenium 50 mcg, and lycopene oil extract 5 mg daily for 8 weeks improves symptoms and peak flow in patients with CP/CPPS when compared with baseline. However, these effects were not observed or were less significant in patients treated with saw palmetto alone (60442).
• Common cold. Although there has been interest in using oral saw palmetto for the common cold, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose.
• Hirsutism. Although there has been interest in using oral and topical saw palmetto for hirsutism, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose.
• Non-neurogenic lower urinary tract symptoms (LUTS). It is unclear if oral saw palmetto is beneficial in females with non-neurogenic LUTS. Details: A small clinical study in elderly Japanese females with LUTS shows that taking saw palmetto extract 320 mg daily for 12 weeks reduces daytime urinary frequency and might improve nocturia, but it does not seem to reduce urinary urgency, incontinence, straining, bladder pain, or urethral pain when compared with placebo (110540).
• Prostate cancer. Small preliminary studies suggest that saw palmetto does not reduce prostate cancer risk or symptoms associated with prostate cancer. Details: Population research shows that people who take saw palmetto supplements do not have a lower risk of developing prostate cancer (15217). Preliminary clinical research also shows that taking saw palmetto 960 mg daily before, during, and after radiation treatment for early prostate cancer does not significantly improve lower urinary tract symptoms when compared with placebo (96412).
• Prostatitis. Adding saw palmetto to antibiotic therapy seems to relieve some symptoms of bacterial prostatitis more effectively than antibiotics alone. Details: Preliminary clinical research in patients with bacterial prostatitis shows that taking saw palmetto extract daily for eight weeks, with prulifloxacin 600 mg daily for 15 days, reduces pain and urinary symptoms more than prulifloxacin alone, but the combination does not appear to improve bacterial eradication or sexual dysfunction more than the antibiotic alone (89442). One small clinical study in patients with chronic nonbacterial prostatitis shows that a specific saw palmetto extract (Prostamol Uno, Profluss) 320 mg daily improves symptoms when compared with no treatment (73329). Combinations of saw palmetto with other supplements have also been used with fluoroquinolone antibiotics, typically resulting in symptom improvement when compared with the antibiotic alone. These supplement combinations include saw palmetto, indole-3-carbinol, and epigallocatexin-3-gallate (Indigal Plus) 2 capsules twice daily for 3 months (73355); saw palmetto 160 mg, stinging nettle 120 mg, curcumin 200 mg, and quercetin 100mg (ProstaMEV plus FlogMEV) for 2 weeks (73346); and saw palmetto 320 mg, Bacillus coagulans 200 mg, and arbutin 100 mg (Lactorepens) daily for 30 days (96411).
• Sexual desire. Although there has been interest in using oral saw palmetto for sexual desire, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose.
• Sexual dysfunction. Although there has been interest in using oral saw palmetto for sexual dysfunction, there is insufficient reliable information about the clinical effects of saw palmetto for this purpose. More evidence is needed to rate saw palmetto for these uses.

(Read more about SAW PALMETTO)

POSSIBLY SAFE ...when the leaves are used orally and appropriately, short-term (4,6,12).

LIKELY UNSAFE ...when large amounts are used long-term. Chronic ingestion of alfalfa has been associated with drug-induced lupus effects (381,14828,30602).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in medicinal amounts. Alfalfa contains constituents with possible estrogenic activity (4,11,30592).

(Read more about ALFALFA)

There is insufficient reliable information available about the safety of American spikenard.

PREGNANCY: POSSIBLY UNSAFE
when used orally; avoid using (12).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about AMERICAN SPIKENARD)

LIKELY SAFE ...when the flower preparations are used orally or topically and appropriately (4,19779,36931,39503,93552,93557,96647,105088).

PREGNANCY: LIKELY UNSAFE
when used orally; contraindicated due to spermatocide, antiblastocyst, and abortifacient effects. There is insufficient reliable information available about the safety of calendula when used topically during pregnancy (4).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about CALENDULA)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Damiana has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12,46933,11866).

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

(Read more about DAMIANA)

LIKELY SAFE ...when used orally and appropriately, short-term. Eleuthero root extract 300-2000 mg has been used safely in clinical trials lasting up to 3 months (730,1427,2574,7522,11099,15586,91509). There is insufficient reliable information available about the safety of eleuthero when used long-term.

CHILDREN: POSSIBLY SAFE
when used orally in adolescents aged 12-17 years, short-term. Eleuthero 750 mg three times daily was used for 6 weeks with apparent safety in one clinical trial (75028). There is insufficient reliable information available about the safety of eleuthero in children or adolescents when used long-term.

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

(Read more about ELEUTHERO)

LIKELY SAFE ...when used orally and appropriately. Saw palmetto has been safely used in clinical studies lasting up to 3 years (2735,6750,6752,6764,6772,6773,11354,14274,15550,17202,17306,17684,73315,73383,73384,73385,73389,89441,96410,96412,110540).

POSSIBLY SAFE ...when used rectally and appropriately. Saw palmetto has been used safely in clinical research at a dose of 640 mg once daily for 30 days (73387). However, the long-term safety of saw palmetto administered rectally is not known.

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally. Saw palmetto has hormonal activity (6766); avoid using.

(Read more about SAW PALMETTO)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, alfalfa might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal research suggests that alfalfa decreases blood sugar in diabetic mice (30605). Also, in one case report, a diabetic patient experienced hypoglycemia after consuming alfalfa extract (30608). Monitor blood glucose levels closely. Dose adjustments might be necessary.

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, alfalfa might interfere with the activity of contraceptive drugs.  Details Alfalfa contains coumestrol, a phytoestrogen, and isoflavonoids, which have estrogenic effects (4,30592).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, alfalfa might interfere with hormone therapy.  Details Alfalfa contains coumestrol, a phytoestrogen, and isoflavonoids, which have estrogenic effects (4,30592).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, alfalfa might decrease the efficacy of immunosuppressive therapy.  Details In vitro research and human case reports suggest that alfalfa may have immunostimulant effects (12174,14828,14829).

PHOTOSENSITIZING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of alfalfa with photosensitizing drugs might have additive effects.  Details Animal research suggests that excessive doses of alfalfa may increase photosensitivity, possibly due to its chlorophyll content (106043). It is unclear if this effect would be clinically relevant in humans.

WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, alfalfa might reduce the anticoagulant activity of warfarin.  Details Alfalfa contains a large amount of vitamin K (4,6). This could theoretically interfere with the activity of warfarin.

(Read more about ALFALFA)

(Read more about AMERICAN SPIKENARD)

CNS DEPRESSANTS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, calendula might have additive effects when used with CNS depressants, although this appears to be unlikely.  Details Although some animal research has suggested that a saponoside constituent in calendula may have sedative effects (39545,39547), calendula has been used for over 30 years without reports of sedation in humans (105088).

(Read more about CALENDULA)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking damiana with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research shows that taking damiana lowers blood glucose level (4,25016).

(Read more about DAMIANA)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro and animal research shows that a constituent of eleuthero, dihydroxybenzoic acid, appears to inhibit platelet aggregation (7592,74976). Concomitant use with anticoagulant or antiplatelet drugs might increase the risk of bleeding.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.  Details Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals (7591,73535,74932,74956,74988,74990). A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels (91509). However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo (12536). These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.  Details In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2 (7532). This effect 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, eleuthero might increase levels of drugs metabolized by CYP2C9.  Details In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9 (7532). This effect has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.  Details In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2D6. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP2D6 drug metabolism (7532,10400).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.  Details In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism (7532,10400).

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Eleuthero might increase serum digoxin levels and increase the risk of side effects.  Details In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal (543). It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay (15585). Although the product was found to be free of digoxin and digitoxin (543), it was not tested for other contaminants (797).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.  Details Animal and in vitro research shows that eleuthero extracts have immunomodulatory effects, including increasing cellular and humoral activity (74887,74915).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.  Details In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1 (35450). Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might increase levels of P-glycoprotein substrates.  Details In vitro research suggests that eleuthero can inhibit the multi-drug transporter protein, P-glycoprotein (22639,91509). However, it is too soon to tell if this is clinically important. This interaction has not been reported in humans.

(Read more about ELEUTHERO)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Saw palmetto might increase the risk of bleeding with anticoagulant or antiplatelet drugs.  Details Saw palmetto is reported to prolong bleeding time (8659). Theoretically, it might increase the risk of bleeding when used concomitantly with anticoagulant or antiplatelet drugs.

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Saw palmetto might reduce the effectiveness of contraceptive drugs.  Details Saw palmetto might have antiestrogenic effects (6766). Theoretically, it might interfere with contraceptive drugs taken concomitantly.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Saw palmetto might reduce the effectiveness of estrogens.  Details Saw palmetto might have antiestrogenic effects (6766). Theoretically, it might interfere with estrogens taken concomitantly.

(Read more about SAW PALMETTO)

General ...Orally, alfalfa leaf seems to be well tolerated. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Abdominal discomfort, diarrhea, and flatulence.
Serious Adverse Effects (Rare):
Orally: Lupus-like syndrome after chronic ingestion of alfalfa.

Dermatologic ...Dermatitis associated with alfalfa use has been reported. In a 1954 publication, dermatitis was noted in a 61-year-old female consuming 4-6 cups of tea made with two tablespoonfuls of alfalfa seeds for approximately two months prior to onset. Examination revealed diffuse, confluent edema and erythema on the face, eyelids, ears, hands, forearms, and distal humeral regions. The dermatitis improved with treatment; re-exposure to alfalfa resulted in a similar reaction (30609).

Endocrine ...Alfalfa contains constituents, including coumestrol, with reported estrogenic activity (30586,30592,4753). Effects in humans are not known.
One case report documents hypokalemia in a female who had been drinking a "cleansing tea" containing alfalfa, licorice, and stinging nettle. The potassium level returned to normal after discontinuing the tea and initiating potassium supplementation. The specific cause of the hypokalemia is not clear. Notably, both stinging nettle and licorice have been associated with hypokalemia and may have been responsible for this effect (30562).

Gastrointestinal ...Orally, flatulence and bulkier feces were reported during the first week of a case series of three subjects ingesting alfalfa (30598). In a case series of 15 patients ingesting alfalfa, increased fecal volume and increased stool frequency was reported. Additional adverse effects included abdominal discomfort in two patients, diarrhea in two patients, loose stools in six patients, and intestinal gas in 13 patients (5816).

Hematologic ...Pancytopenia and splenomegaly were reported in a 59-year-old male who had been taking 80-160 grams of ground alfalfa seeds for up to six weeks at a time, for a five month period. Hematologic values and spleen size returned to normal when alfalfa was discontinued (381).

Other ...Alfalfa products, including sprouts, seeds, and tablets, have been found to be contaminated with Escherichia coli, Salmonella, and Listeria monocytogenes, which have caused documented infections (5600,30566,30568,30572,30569,30564,30604,30610,30563,30607) (30566,30564,30604,30610,30563,30607,30576).
Orally, alfalfa has been associated with the development of a lupus-like syndrome in animals and humans (30594,14828,14830,30602), as well as with possible exacerbations of lupus in patients with known systemic lupus erythematosus (SLE). These reactions may be associated with the amino acid L-canavanine (30594), which appears to be present in alfalfa seeds and sprouts, but not leaves, and therefore should not be present in alfalfa tablets manufactured from the leaves (30601). However, case reports have included individuals ingesting tablets. A lupus-like syndrome was described in four patients taking 12-24 alfalfa tablets per day. Symptoms included arthralgias, myalgias, and rash; positive antinuclear antibodies (ANA) arose anywhere from three weeks to seven months after initiating alfalfa therapy. Upon discontinuation of alfalfa tablets, all four patients became asymptomatic. In two patients, ANA levels normalized (14828). Two additional reports have documented possible exacerbation or induction of SLE associated with alfalfa use. One case involved a female with a 26-year history of SLE, who had been taking 15 tablets of alfalfa daily for nine months prior to an exacerbation. Because of the delay in onset of the exacerbation from the initiation of alfalfa therapy, causation cannot be clearly established (30575). In a different report, SLE and arthritis were found in multiple family members who had been taking a combination of vitamin E and alfalfa tablets for seven years (30602). It is not known what other environmental or genetic factors may have affected these individuals, and the association with alfalfa is unclear.

(Read more about ALFALFA)

General ...No adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.

(Read more about AMERICAN SPIKENARD)

General ...Orally and topically, calendula is generally well tolerated.
Serious Adverse Effects (Rare):
All ROAs: Allergic reactions.

Dermatologic ...Topically, a preparation containing calendula powder 0. 1% resulted in inflammation around the wound to which it was applied (96647). Burning sensation, itching, redness, and scaling were reported rarely in patients applying a combination of calendula, licorice, and snail secretion filtrate to the face. The specific role of calendula is unclear (110322).

Immunologic ...Orally, calendula can cause allergic reactions. Topically, calendula can cause eczematous allergic reactions. Calendula-specific patch testing is recommended prior to usage to determine allergenic potential. Testing is particularly necessary in individuals sensitive to the Asteraceae/Compositae family (10691,11458,96647). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. A preparation containing calendula powder 0.1% resulted in hives in a patient with a ragweed allergy (96647). Despite the widespread use of calendula and the occurrence of allergies to other family members, there has been only one report of anaphylaxis (11152).

(Read more about CALENDULA)

General ...Orally, adverse effects to damiana seem to be rare; however, a thorough safety evaluation has not been conducted.

Neurologic/CNS ...Orally, 200 grams of damiana extract has caused tetanus-like convulsions and paroxysms resulting in symptoms similar to rabies or strychnine poisoning (4).

(Read more about DAMIANA)

General ...Orally, eleuthero root is generally well tolerated when used short-term.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, gastrointestinal upset, headache, nausea, and urticaria.

Cardiovascular ...Orally, increased blood pressure has been reported in children with hypotension taking eleuthero in one clinical study (74980). Eleuthero has been reported to cause tachycardia, hypertension, and pericardial pain in patients with rheumatic heart disease or atherosclerosis. It is unclear if these effects were caused by eleuthero, or by the cardioglycoside-containing herb, silk vine (Periploca sepium), which is a common adulterant found in eleuthero products (12,797,6500).

Dermatologic ...Orally, eleuthero has been reported to cause rash in some clinical studies (75013,75028).

Gastrointestinal ...Orally, eleuthero has been reported to cause dyspepsia, nausea, diarrhea, and gastrointestinal upset in some patients (74938,75028,91510).

Genitourinary ...Orally, mastalgia and uterine bleeding were reported in 7. 3% of females taking eleuthero 2 grams daily in one clinical study (6500,11099). These adverse effects seem to be more likely with higher doses.

Neurologic/CNS ...Orally, headaches have been reported in 9. 8% of people taking eleuthero in one clinical study (11099).
In one case report, a 53-year-old female developed spontaneous subarachnoid hemorrhage associated with the use of an herbal supplement containing red clover, dong quai, and eleuthero (70419). It is unclear if this event was related to the use of eleuthero, the other ingredients, the combination, or another cause entirely.

Psychiatric ...Orally, nervousness has been reported in 7. 3% of people taking eleuthero in one clinical study (11099). Eleuthero has also been reported to cause slight anxiety, irritability, and melancholy in some patients (6500,11099). These adverse effects seem to be more likely to occur with higher doses.

(Read more about ELEUTHERO)

General ...Orally, saw palmetto is well tolerated and adverse effects are mild, infrequent, and reversible.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, decreased libido, diarrhea, dizziness, fatigue, headache, nausea, rhinitis, vomiting.

Cardiovascular ...Occasionally, cases of hypertension, postural hypotension, tachycardia, angina pectoris, arrhythmia, extrasystole, angiopathy, myocardial infarction, and congestive heart failure have been reported in patients using saw palmetto orally (6424,6484,6752,6772,17684,73388,89441). One case of severe bradycardia and second degree heart block was reported in a 64 year-old male taking an unknown amount of saw palmetto for a few weeks (96413).

Dermatologic ...A case report describes a 61-year-old male who developed a fixed drug eruption with localized blisters and erosions three days after starting oral saw palmetto. The lesions resolved when saw palmetto was stopped, but recurred when it was reintroduced six months later. Topical corticosteroid treatment was necessary and the patient was left with some residual hyperpigmented patches (104805). A combination of saw palmetto and beta-sitosterol has been associated with a single report of worsening acne (15550).

Endocrine ...Two case reports involving one 11-year-old female undergoing treatment for telogen effluvium and another 10-year-old female undergoing treatment for hirsutism, describe hot flashes and the onset of menarche associated with use of saw palmetto. One of these patients was consuming saw palmetto in a food supplement; the other was taking a supplement containing saw palmetto 320 mg daily (73361,96414). In both cases, the hot flashes resolved following treatment discontinuation. In one case, a rechallenge with saw palmetto caused a recurrence of hot flashes.

Gastrointestinal ...Gastrointestinal complaints such as nausea, vomiting, constipation, diarrhea, gastralgia, and halitosis are the most frequently reported adverse effects associated with saw palmetto (6484,6752,60442,73315,73320,73348,73354,73383,73385,73388,89441). Less often, cases of duodenal ulcer, dyspepsia, or heartburn have been reported (6772,73329,73354). Meteorism (intestinal gas accumulation) has also been reported with saw palmetto, although causality was unclear (60442).

Genitourinary ...Some clinicians are concerned that saw palmetto might cause erectile dysfunction, ejaculatory disturbance, or altered libido because of its potential effects on 5-alpha-reductase. Some preliminary clinical studies have reported sexual dysfunction, particularly ejaculatory dysfunction, erectile dysfunction, and reduced libido, in patients taking saw palmetto (5093,17202,17684,73383,89441). However, most of these patients were previously diagnosed with prostate disorders, so causality is unclear. Additionally, several clinical studies indicate that the occurrence of impotence in males taking saw palmetto is similar to placebo and tamsulosin (Flomax), and significantly less than finasteride (Proscar) (2732,6424,17306,107481). Rarely, cases of testicular pain, vesical tenesmus, and urinary tract infections have been reported in patients using saw palmetto extract orally (73388).

Hematologic ...Saw palmetto might have antiplatelet effects and potentially increase the risk of bleeding in some patients. There is one report of excessive intraoperative bleeding in a patient who took saw palmetto prior to surgery. Bleeding time normalized when saw palmetto was discontinued (8659). Also, one case of cerebral hemorrhage has been reported, but details are not available to determine causality (6772,73348). A case of retroperitoneal hematoma after bilateral inguinal hernia repair is reported in a male patient taking saw palmetto. The patient was discharged after a 3-day hospitalization in stable condition (112177).

Hepatic ...A case report describes a patient who developed acute hepatitis and pancreatitis while taking saw palmetto. Symptoms resolved when saw palmetto was discontinued, and reemerged upon re-challenge (14457). Other cases of acute hepatitis and pancreatitis, with elevated alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin have been reported in patients using saw palmetto orally (14457,73350,73351).

Musculoskeletal ...Orally, saw palmetto may cause fatigue, weakness, muscle pain, and back pain, although these adverse events are rare (6424,73388,89441). A case of saw palmetto-related rhabdomyolysis was reported in an 82-year-old male presenting with kidney dysfunction, increased C-reactive protein levels, and elevated serum creatine kinase (73358).

Neurologic/CNS ...Orally, saw palmetto can cause headaches, dizziness, insomnia, and fatigue (6750,6752,6772,11354,60442,73348,73385,73388,89441).

Ocular/Otic ...A case of intraoperative floppy-iris syndrome (IFIS) has been reported in a patient using saw palmetto orally (73340). However, no statistically significant association between saw palmetto and IFIS was found in a case series of 660 patients undergoing cataract surgery (73347).

Pulmonary/Respiratory ...Rhinitis is one of the more commonly reported adverse effects of saw palmetto (73348). One patient taking saw palmetto extract 160 mg twice daily reported "breathlessness" (73388). Two cases of respiratory depression have been reported in patients using saw palmetto extract (Permixon) 320 mg (6772).

(Read more about SAW PALMETTO)