3-In-1 Hair Growth Formula by iRestore

LIKELY EFFECTIVE

• Benign prostatic hyperplasia (BPH). Oral beta-sitosterol is beneficial for most symptoms of BPH. Details: Taking beta-sitosterol 60-130 mg orally in 2-3 divided doses daily for up to 18 months significantly improves urinary symptoms, increases maximum urinary flow, and decreases postvoid residual urine volume; however, it does not affect prostate size (5327,5328,5329,7195,7198,34975). Additionally, one study suggests that taking an enriched form of saw palmetto oil (Vispo) 200 mg containing 3% beta-sitosterol twice daily for 12 weeks seems to be more effective than standard saw palmetto oil containing 0.3% beta-sitosterol for reducing some measures of overall symptoms of BPH (104803). Although some preliminary research shows no benefit of beta-sitosterol on symptoms of BPH, the variability in doses used, the short duration of treatment, the small study sizes, and the differing severity of disease at baseline limit the reliability of these latter results (35124,96784).
• Hypercholesterolemia. Oral beta-sitosterol is beneficial for hypercholesterolemia. Details: Taking beta-sitosterol orally significantly reduces total and low-density lipoprotein (LDL) cholesterol levels, but has little or no effect on high-density lipoprotein (HDL) cholesterol levels. Beta-sitosterol 0.65-1.5 grams twice daily has been used, typically in conjunction with a low-fat diet (6668,7195,112081). The effects of combination formulations containing beta-sitosterol have also been evaluated in patients with hypercholesterolemia. Some preliminary clinical research in these patients shows that taking a combination of soy protein 8 grams plus beta-sitosterol 2 grams daily for 40 days lowers LDL cholesterol by 17-20 mg/dL, but does not improve triglyceride or HDL cholesterol levels, when compared to baseline (35013,35039). Other clinical research shows that taking a combination of beta-sitosterol 2.5 grams daily along with cholestyramine (Questran, Bristol Myer Squibb) 8 grams daily for 12 weeks reduces total cholesterol by about 23 mg/dL and LDL cholesterol by 15 mg/dL when compared to baseline, but is less effective than atorvastatin 10 or 80 mg daily (35100).

POSSIBLY EFFECTIVE

• Coronary heart disease (CHD). The US Food and Drug Administration (FDA) has approved an authorized health claim for dietary plant sterols, when taken in doses of at least 3.4 grams daily as part of a diet low in saturated fat and cholesterol, for reducing the risk of CHD. Details: In 2010, the FDA authorized a health claim stating that consuming at least 3.4 grams of plant sterols daily, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease (102365). This health claim is based on evidence showing that plant sterols can lower cholesterol levels. However, there is currently no evidence directly linking dietary intake of plant sterols with a reduced risk for developing CHD.
• Familial hypercholesterolemia. Oral beta-sitosterol, in combination with a cholesterol-lowering diet, seems to reduce low-density lipoprotein (LDL) cholesterol levels in patients with familial hypercholesterolemia. However, it doesn't seem to work as well as sitostanol or bezafibrate. Details: Preliminary clinical research shows that taking beta-sitosterol for 1-4 months while following a cholesterol-lowering diet reduces total cholesterol by 6% to 13% and LDL cholesterol by 6% to 20% in adult and pediatric patients with familial hypercholesterolemia. Beta-sitosterol 2.5-21.1 grams taken in up to three divided doses daily for 1-3 months has been used in adults. Beta-sitosterol 2-4 grams three times daily for 3 months has been used in children and adolescents (3889,5331,5332,5333,35067). Some research suggests that the optimal dose of beta-sitosterol is 6 grams daily; higher doses do not appear to be more effective (5333). However, some research in pediatric patients shows that beta-sitosterol can also decrease levels of high-density lipoprotein (HDL) cholesterol (5332) and that beta-sitosterol appears to be less effective for reducing LDL cholesterol when compared to sitostanol (3889). Furthermore, beta-sitosterol does not appear to improve triglyceride levels (5333). Some research has compared beta-sitosterol to cholesterol-lowering medication. In children with familial hypercholesterolemia, taking beta-sitosterol 1 grams three times daily in combination with the fibrate drug bezafibrate 200 mg once daily for 24 months reduces cholesterol as effectively as taking bezafibrate 200 mg twice daily. However, taking beta-sitosterol 2 grams three times daily is less effective for lowering LDL cholesterol when compared with bezafibrate 200 mg twice daily (5334).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there is interest in using oral beta-sitosterol for allergic rhinitis, there is insufficient reliable information about the clinical effects of beta-sitosterol for this condition.
• Androgenic alopecia. Oral beta-sitosterol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in males with androgenic alopecia shows that a combination of beta-sitosterol 50 mg plus saw palmetto extract 200 mg taken twice daily for an average of 4.6 months improves subjective scores of hair quantity and quality when compared with baseline (15550). The validity of this finding is limited by the lack of a comparator group.
• Asthma. Although there is interest in using oral beta-sitosterol for asthma, there is insufficient reliable information about the clinical effects of beta-sitosterol for this condition.
• Burns. Topical beta-sitosterol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying an ointment containing sesame oil, beta-sitosterol, berberine, and other plant ingredients (MEBO) is as effective as applying silver sulfadiazine dressing twice daily for healing burns and preventing bacterial infection (13526). Furthermore, this ointment appears to be more effective than povidone-iodine plus bepanthenol cream for reducing pain. The ointment can also shorten the hospital stay of these patients by almost one day when compared with povidone-iodine plus bepanthenol (35118). However, when used for second-degree facial burns, this ointment increases healing time by about 2 days and worsens pain and discomfort when compared with a specific dressing containing ionic silver (Aquacel Ag Hydrofiber) (35117). The ointment has been applied to partial-thickness burns as a thick layer every 4-12 hours for up to 18 days or until release from the hospital in patients aged 2 years and older (13526,35117,35118).
• Cancer. It is unclear if dietary beta-sitosterol is beneficial for cancer prevention. Details: A meta-analysis of population research has found that although the highest intake of plant sterols is associated with a reduced risk of having cancer when compared with the lowest intake, there is no association between beta-sitosterol itself and cancer risk (106084). Also, population research suggests that dietary intake of beta-sitosterol does not affect the risk of colon cancer (34993).
• Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). Although there is interest in using oral beta-sitosterol for prostatitis, there is insufficient reliable information about the clinical effects of beta-sitosterol for this condition.
• Esophageal cancer. It is unclear if dietary beta-sitosterol intake influences the outcome of esophageal cancer. Details: In Chinese people with esophageal squamous cell carcinoma, the mortality rate does not seem to differ between those with the lowest versus the highest intake of dietary beta-sitosterol, measured five years before diagnosis (112082).
• HIV/AIDS. Although there is interest in using oral beta-sitosterol for HIV/AIDS, there is insufficient reliable information about the clinical effects of beta-sitosterol for this condition.
• Menopausal symptoms. Although there is interest in using oral beta-sitosterol for menopausal symptoms, there is insufficient reliable information about the clinical effects of beta-sitosterol for this purpose.
• Migraine headache. Although there is interest in using oral beta-sitosterol for migraine headache, there is insufficient reliable information about the clinical effects of beta-sitosterol for this condition.
• Obesity. It is unclear if oral beta-sitosterol is beneficial for obesity. Details: In Chinese adults, higher dietary intake of beta-sitosterol is inversely related to the risk of being overweight. The risk of central obesity specifically is linked to beta-sitosterol intake in males (112083).
• Psoriasis. Although there is interest in using oral beta-sitosterol for psoriasis, there is insufficient reliable information about the clinical effects of beta-sitosterol for this condition.
• Rheumatoid arthritis (RA). It is unclear if oral beta-sitosterol is beneficial for RA. Details: Preliminary clinical research shows that taking a specific supplement (Moducare) containing beta-sitosterol 20 mg and beta-sitosterol glucoside 0.2 mg three times daily for 24 weeks improves pain and symptoms in 28% to 85% of patients with RA when compared with baseline (35200). The validity of this finding is limited by the lack of a comparator group.
• Systemic lupus erythematosus (SLE). Although there is interest in using oral beta-sitosterol for SLE, there is insufficient reliable information about the clinical effects of beta-sitosterol for this condition.
• Thrombocytopenia. Although there is interest in using oral beta-sitosterol for thrombocytopenia, there is insufficient reliable information about the clinical effects of beta-sitosterol for this condition.
• Tuberculosis. It is unclear if oral beta-sitosterol is beneficial for tuberculosis. Details: A small clinical trial shows that taking beta-sitosterol orally as an adjunct to conventional treatment for tuberculosis can increase lymphocyte counts when compared with placebo; however, beta-sitosterol does not seem to decrease the time to cure based on negative sputum culture (5337).
• Upper respiratory tract infection (URTI). Although there is interest in using oral beta-sitosterol for upper respiratory infections such as bronchitis, common cold, exercise-induced respiratory infections, and influenza, there is insufficient reliable information about the clinical effects of beta-sitosterol for these conditions.
• Wound healing. Although there is interest in using topical beta-sitosterol for wound healing, there is insufficient reliable information about the clinical effects of beta-sitosterol for this purpose. More evidence is needed to rate beta-sitosterol for these uses.

(Read more about BETA-SITOSTEROL)

LIKELY EFFECTIVE

• Biotin deficiency. Oral and injectable biotin prevents and treats biotin deficiency. Details: Biotin up to 10 mg daily has been used to treat and prevent biotin deficiency. Injections of biotin 150 mcg daily for 3-5 days have been used in adults. Biotin deficiency might occur due to different etiologies such as inherited biotinidase deficiency, malnutrition, chronic use of anticonvulsants, pregnancy, and excessive and chronic raw egg consumption (6243,19347). A very small study in newborns aged 1-6 months shows that adding biotin to infant formula safely improves biotin status in formula-fed infants (111365). The validity of these findings is limited by a lack of blinding, no randomization, and the small sample size.

POSSIBLY INEFFECTIVE

• Multiple sclerosis (MS). In spite of contrary reports, high-dose biotin (300 mg daily) does not reduce disability in patients with progressive MS. It also does not seem to be linked to an increased risk for relapse. Details: Although most earlier research suggested benefit, the highest quality evidence shows that high-dose biotin does not improve outcomes in progressive MS (95662,102963,102966,104011). A large multi-centered randomized clinical trial (SPI2) in patients with progressive MS and high disability shows that taking biotin 100 mg three times daily for 15 months does not improve disability, as measured on the expanded disability status scale (EDSS), or 25-foot walking time, when compared with placebo. The SPI2 clinical trial also did not find that biotin increases the rate of relapse (104011), a concern raised in one observational study of high-dose biotin (104000). Also, a large observational study of adults with progressive MS failed to identity an increase in annualized relapse rates in patients that reported taking biotin when compared with controls (105716). Other observational research has also found no effect on the relapse risk (102963,102964). There is some speculation that any increased rate of relapse identified in some high-dose biotin cohorts might be due to detection bias or reduced compliance with disease-modifying therapies.
• Seborrheic dermatitis. Oral biotin doesn't seem to improve seborrheic dermatitis of infancy. Details: A clinical trial in infants with seborrheic dermatitis shows that biotin given by mouth does not improve symptoms when compared with placebo (8469).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alopecia areata. It is unclear if oral biotin is beneficial for alopecia areata. Details: A small clinical study in healthy adults with alopecia areata shows that weekly injections of intramuscular biotin 5 mg/1 mL and dexpanthenol 250 mg/2 mL for 6 weeks reduces hair fall count and transiently increases hair density compared with baseline (111366). The validity of these findings is limited by a lack of a placebo control group, small sample size, and short duration of treatment. It is unclear if the effects are due to biotin, dexpanthenol, or the combination. Another small clinical study in 9-year-old children with alopecia areata shows that taking biotin 20 mg with zinc aspartate 100 mg orally along with topical application of clobetasol propionate 0.025% daily for one year promotes hair regrowth in 33% of children, compared with 0% in the group receiving the steroid deflazacort (6932). It is unclear if these effects are due to biotin, zinc, topical clobetasol, or the combination.
• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). Although there is interest in using oral biotin for ALS, there is insufficient reliable information about the clinical effects of biotin for this condition.
• Biotin-thiamine-responsive basal ganglia disease. Adding oral biotin to oral thiamine does not seem to improve most symptoms associated with this condition, although it may slightly speed recovery from acute crisis in children. Details: A small case series in children ages 1-12 years with biotin-thiamine-responsive basal ganglia disease has found that adding biotin 5 mg/kg daily to thiamine 40 mg/kg daily for 30 months is not associated with additional symptomatic improvement in encephalopathy, seizures, dystonia, or other neurologic sequelae when compared with taking only thiamine. However, taking biotin with thiamine is associated with a 1-day reduction in recovery from acute crisis when compared with thiamine alone (95661).
• Brittle nails. Low quality clinical studies suggest that oral biotin might improve nail thickness and prevent the splitting of brittle nails. Details: Some small, low quality clinical studies in people with brittle nails shows that taking biotin 2.5 mg orally daily for 1.5 to 15 months increases nail thickness and decreases the splitting of fingernails and toenails in some people when compared with baseline (171,35593). The validity of these findings is limited by the small study sizes and the lack of a comparator group.
• Depression. Although there is interest in using oral biotin for mild depression, there is insufficient reliable information about the clinical effects of biotin for this condition.
• Diabetes. It is unclear if oral biotin is beneficial for type 2 diabetes. Details: A meta-analysis of randomized controlled trials shows that taking biotin 1.5-15 mg orally daily for 1-3 months does not improve fasting blood glucose or serum insulin levels when compared with placebo. However, the validity of these results is limited by inclusion of subjects with and without diabetes (110044). A very small study in adults with type 2 diabetes also shows that taking biotin 5 mg three times daily for 28 days does not affect glucose or insulin levels when compared to baseline (11579). Biotin has also been studied in combination with other ingredients. Preliminary clinical research shows that a taking a specific supplement containing a combination of biotin 2 mg and chromium picolinate 600 mcg (Diachrome, Nutrition 21) can lower blood glucose and glycated hemoglobin levels in patients with type 2 diabetes who are poorly controlled on oral hypoglycemic drugs (12385,12390,15169). It is unclear if these effects are due to biotin, chromium, or the combination.
• Diabetic neuropathy. Although there is interest in using oral and intramuscular biotin for diabetic neuropathy, there is insufficient reliable information about the clinical effects of biotin for this condition.
• Muscle cramps. It is unclear if biotin is beneficial for improving muscle cramps in patients undergoing hemodialysis. Details: Patients undergoing hemodialysis are prone to muscle cramps. A small clinical study in patients with hemodialysis-related muscle cramps shows that taking biotin 1 mg in the morning daily for at least one week prevents and reduces severity of muscle cramps when compared to baseline. Cessation of biotin led to recurrence of cramps, and restarting oral biotin led to resolution of cramps during hemodialysis (89475). The validity of these findings is limited by the lack of comparator group. More evidence is needed to rate biotin for these uses.

(Read more about BIOTIN)

LIKELY EFFECTIVE

• Familial hypercholesterolemia. Oral plant sterols are beneficial for reducing levels of low-density lipoprotein (LDL) cholesterol when used in combination with a cholesterol-lowering diet in children and adults with familial hypercholesterolemia (FH). Details: A meta-analysis of results from clinical research in children and adults with FH shows that taking plant sterols while following a cholesterol-lowering diet reduces total cholesterol by an additional 12 mg/dL and LDL cholesterol by an additional 23 mg/dL when compared with following a cholesterol-lowering diet alone (90743). Individual clinical trials in adults and children 5 years and up show that consuming margarine spreads or yogurt enriched with plant sterol 1.6-2.3 grams daily for 4-26 weeks, sometimes in combination with statin therapy, reduces total cholesterol by up to 11% and LDL cholesterol by up to 14% in patients with FH (90726,90731,35037,35106). However, most clinical research shows that plant sterols do not reduce triglyceride levels or increase high-density lipoprotein (HDL) cholesterol levels in patients with FH (35037,35106,90743).
• Hypercholesterolemia. Oral plant sterols in doses of 2-3 grams daily are beneficial for reducing levels of low-density lipoprotein (LDL) cholesterol, but not triglycerides, when used in combination with a cholesterol-lowering diet. Details: Clinical research shows that taking plant sterols, alone or in combination with plant stanols, reduces total and LDL cholesterol levels in patients with hypercholesterolemia. Taking plant sterols daily while following a cholesterol-lowering diet reduces total cholesterol by about 3% to 8% and LDL cholesterol by about 5% to 15% when compared with dieting alone (5336,5437,7105,65749,90686,90720,90722,90723,90724,90734)(90741,90748,90752,106093). Plant sterols seem to have the most significant cholesterol-lowering effect in people who naturally produce a high amount of cholesterol (90742). When taken along with statin therapy, plant sterols can lower total cholesterol by about 12-22 mg/dL and LDL cholesterol by about 11-16 mg/dL when compared with statin therapy alone (90728,96272). Predictive modeling suggests that the cholesterol reduction from plant sterols can reduce the risk of cardiovascular disease over time. In English adults with hypercholesterolemia and no cardiovascular disease, replacing regular spreads with plant sterol -enriched spreads over a 20-year period could potentially prevent 69 cardiovascular events per 10,000 males and 40 events per 10,000 females (98449). Plant sterols, usually as esters, with or without plant stanols, 0.2-9 grams daily for up to one year have been used (5336,5437,5814,7105,14298,90686,90720,35034,90722,90723)(90724,90726,90730,90732,90733,90734,90741,90742,90744,90748)(90752,96272). However, the optimal dosage of plant sterols for reducing LDL cholesterol is about 2-3 grams daily taken with meals (5814,90733,90748). At this dosage, plant sterols seem to work as well as plant stanols but less effectively than taking policosanol 5-40 mg daily (14298,90730). When taken as fortified foods, plant sterols appear to be more effective when taken in dairy products than in breads or cereals (35034). No increased benefit is seen at dosages higher than 2-3 grams daily (90744). In post-menopausal females, a meta-analysis of 6 studies shows that plant sterols are most effective for reducing total and LDL cholesterol in patients with obesity, using a daily dose of plant sterols greater than 2 grams, and duration of treatment greater than 8 weeks (112081). Additionally, some clinical research shows that plant sterols might become less effective after about 2-3 months of treatment (90726). Results from most individual clinical studies show that plant sterols do not reduce triglyceride levels in patients with hypercholesterolemia (65749,90720,90732,96272,106093,112081). However, a meta-analysis of results from 12 clinical studies shows that taking plant sterols 0.8-4 grams daily reduces triglyceride levels by 6% in patients with hypercholesterolemia (90732). This suggests that plant sterols might modestly lower triglyceride levels in some patients, but more research in larger patient populations is needed to confirm this finding. There is also some evidence showing that plant sterols prepared as ester derivatives using fish oil rather than sunflower oil, olive oil, or rapeseed oil can moderately lower triglyceride levels when compared with placebo (90739). However, this benefit is likely due to the triglyceride-lowering activity of fish oil rather than plant sterols. Taking plant sterols does not improve levels of high-density lipoprotein (HDL) cholesterol (65749,90728,90732,96272,112081).

POSSIBLY EFFECTIVE

• Coronary heart disease (CHD). The US Food and Drug Administration (FDA) has approved an authorized health claim for dietary plant sterols, when taken in doses of at least 3.4 grams daily as part of a diet low in saturated fat and cholesterol, for reducing the risk of CHD. Details: In 2010, the US FDA authorized a health claim stating that consuming at least 3.4 grams of plant sterols daily, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease (102365). This health claim is based on evidence showing that plant sterols can lower cholesterol levels. However, there is currently no evidence directly linking dietary intake of plant sterols with a reduced risk for developing CHD.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cancer. It is unclear if dietary plant sterols are beneficial for cancer prevention. Details: A meta-analysis of population research has found that the highest intake of plant sterols is associated with a 37% reduced risk of cancer when compared with the lowest intake (106084).
• Colorectal cancer. It is unclear if dietary plant sterols are beneficial for colorectal cancer prevention. Details: Population research has found that dietary intake of specific plant sterols, including campesterol, stigmasterol, or beta-sitosterol, is not associated with risk of developing colon cancer. Dietary intake of plant sterols also does not affect the risk of rectal cancer in females; however, in males, higher dietary intake of the plant sterols campesterol or stigmasterol is associated with an INCREASED risk of rectal cancer (34993).
• Esophageal cancer. It is unclear if dietary plant sterols influence the outcome of esophageal cancer. Details: In Chinese people with esophageal squamous cell carcinoma, the mortality rate does not seem to differ between those with the lowest versus the highest intake of dietary plant sterols, measured five years before diagnosis (112082).
• Gastric cancer. It is unclear if dietary plant sterols are beneficial for gastric cancer prevention. Details: Population research has found that consuming at least 82.5 mg of plant sterols daily as part of the diet is associated with moderately lower odds of developing gastric cancer when compared to those who consume less than 45.5 mg daily (34984).
• Impaired glucose tolerance (prediabetes). Although there is interest in using oral plant sterols for prediabetes, there is insufficient reliable information about the clinical effects of plant sterols for this condition.
• Metabolic syndrome. It is unclear if oral plant sterols are beneficial for metabolic syndrome; the available research is conflicting. Details: One clinical study shows that taking yogurt mini-drinks providing plant sterols 2 grams twice daily for 8 weeks reduces total cholesterol by about 16%, low-density lipoprotein (LDL) cholesterol by about 20%, and triglyceride levels by about 19% when compared with control yogurt drinks without plant sterols (90749). However, results from a much smaller study in patients with metabolic syndrome shows that taking plant sterols 2 grams daily for 8 weeks in breakfast cereal and margarine does not improve plasma lipids or other cardiovascular markers when compared with placebo foods (90745). Reasons for the discrepancy are not clear but might relate to the dose or formulation of plant sterol, or the lipid levels of the patients at baseline.
• Myocardial infarction (MI). It is unclear if dietary plant sterols are beneficial for MI prevention. Details: Population research has found that consuming approximately 340 mg of plant sterols daily is associated with a 29% lower risk of first myocardial infarction in males when compared with those who consume about 150 mg daily. However, dietary plant sterol intake is not associated with a reduced risk of first myocardial infarction in females (90740).
• Obesity. It is unclear if oral plant sterols are beneficial for obesity. Details: In Chinese adults, higher dietary intakes of beta-sitosterol, stigmasterol, and total plant sterols are inversely related to the risk of being overweight. The risk of central obesity is linked to stigmasterol intake in females, and to beta-sitosterol intake in males (112083). Preliminary clinical research in obese individuals shows that consuming rice bran snack bars fortified with a mixture of plant sterols and stanols 1.8 grams daily for 8 weeks while following a reduced calorie diet does not increase weight loss, reduce low-density lipoprotein (LDL) cholesterol, or improve blood glucose control when compared to dieting and consuming unfortified rice bran snack bars. However, the plant sterol-enriched rice bran snacks appear to decrease total cholesterol by about 10% more than unfortified rice bran snacks (90738). More evidence is needed to rate plant sterols for these uses.

(Read more about PLANT STEROLS)

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.

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LIKELY SAFE ...when used orally and appropriately. Beta-sitosterol has been safely used at a dose of 130 mg daily for up to 18 months or a dose of up to 21.1 grams daily for up to 3 months (5327,5328,5329,5330,5331,5332,5333,5334,5336,5337) (7198,10638). There is insufficient reliable information available about the safety of beta-sitosterol when used topically.

CHILDREN: LIKELY SAFE
when used orally and appropriately. Beta-sitosterol has been safely used at a dose of 2-4 grams three times daily for up to 3 months (3889,5331,5332,5333,5334,35067).

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

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LIKELY SAFE ...when used orally and appropriately. Biotin has been safely used in doses up to 300 mg daily for up to 6 months. A tolerable upper intake level (UL) has not been established (1900,6243,95662,102965). ...when applied topically as cosmetic products at concentrations of 0.0001% to 0.6% biotin (19344).

POSSIBLY SAFE ...when used intramuscularly and appropriately (8468,111366).

CHILDREN: LIKELY SAFE
when used orally and appropriately. Biotin has been safely used at adequate intake doses of 5-25 mcg daily for up to 6 months (173,6243,19347,19348,111365). A tolerable upper intake level (UL) has not been established.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Biotin has been safely used at the adequate intake (AI) dose of 30 mcg daily during pregnancy and 35 mcg daily during lactation. It has also been used in supplemental doses of up to 300 mcg daily (6243,7878). A tolerable upper intake level (UL) has not been established.

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LIKELY SAFE ...when used orally and appropriately. Plant sterols have been safely used in studies lasting up to one year (35022,35037,90724,90726,90730,90732,90733,90734,90739,90742). Due to the unknown safety of plant sterol oxidation products, and the known production of these oxidation products during the heating of foods (106092), there is insufficient reliable information available about the safety of heat-treated foods containing added plant sterols.

CHILDREN: LIKELY SAFE
when used orally and appropriately. Plant sterols have been safely used in children in studies lasting for up to 6 months (35037,90722,90723,90726,90731,35106). PREGNANCY AND LACTATION: Insufficient reliable information available; avoid using.

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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.

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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.

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General ...Orally, beta-sitosterol is generally well tolerated. Topically, beta-sitosterol seems to be well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, gas, indigestion, and nausea.

Dermatologic ...Orally, beta-sitosterol can worsen acne when taken alone or in combination with saw palmetto (5331,15550).

Gastrointestinal ...Orally, beta-sitosterol can cause nausea, indigestion, gas, diarrhea, or constipation (5327,5328). Beta-sitosterol can also reduce the appetite (5334). There is a case report of acute pancreatitis thought to be associated with taking beta-sitosterol in a 57-year-old male. Symptoms started the first day of use, but did not return when he stopped taking beta-sitosterol (106080).
Single reports of reduced appetite, flatulence, and diarrhea have been reported for patients taking a combination of saw palmetto and beta-sitosterol (15550).

Genitourinary ...Orally, beta-sitosterol can cause erectile dysfunction and loss of libido (5327,5329).

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General ...Orally and topically, biotin is generally well tolerated.
Most Common Adverse Effects: None.

Gastrointestinal ...Orally, high-dose biotin has been rarely associated with mild diarrhea. Transient mild diarrhea was reported by 2 patients taking biotin 300 mg daily (95662).

Pulmonary/Respiratory ...In one case report in France, a 76-year-old female frequent traveler developed eosinophilic pleuropericarditis after taking biotin 10 mg and pantothenic acid 300 mg daily for 2 months. She had also been taking trimetazidine for 6 years (3914). Whether eosinophilia in this case was related to biotin, pantothenic acid, other substances, or patient-specific conditions is unknown. There have been no other similar reports.

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General ...Orally, plant sterols are generally well tolerated.

Dermatologic ...Acute dermatitis has been reported in a case report of a 51-year-old female who used a pharmacy-brand plant sterol supplement to lower cholesterol levels. The rash was widespread with lesions on the hands and feet and a red and swollen face. The patient was treated orally with prednisolone and topically with emollients for 2 weeks (90737). It is not entirely clear if this adverse effect was due to the plant sterol supplement or another contributing factor.

Endocrine ...Peripheral precocious puberty has been described in a 20-month-old boy who ingested about 15 grams daily of a chicken essence product containing the plant sterol avenasterol, also known as clerosterol or chondrillasterol. Signs and symptoms included elevated estradiol and testosterone levels, acne, hairiness, increased penis size, hoarse voice, and increased growth rate. These effects were reversed when the product was stopped (112084).

Gastrointestinal ...Abdominal discomfort has occurred in one child in a clinical trial of oral plant sterols (35106). Because plant sterols decrease cholesterol absorption in the gut, there is concern that they might produce some gastrointestinal symptoms like diarrhea and excess amounts of fat in the stool (steatorrhea), although these adverse effects have not been reported in clinical research.

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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).

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