Gentle Lax [Discontinued] by Mountain Meadow Herbs

POSSIBLY EFFECTIVE

• Acne. Topical aloe gel may reduce acne lesions when used with topical tretinoin in children and adults with acne. Details: One clinical trial in children and adults with acne shows that topical application of a gel containing aloe 50% in the morning and evening, in addition to topical application of tretinoin 0.025% cream and twice daily cleansing with a medical soap, improves acne lesions by approximately 35% more than using the same treatments without aloe (90124).
• Burns. Topical aloe gel or cream may reduce healing time in patients with superficial or partial thickness burns. Details: A meta-analysis of four small clinical trials in patients with second-degree burns shows that use of topical aloe vera reduces time to healing by about 4.4 days when compared to control groups treated with silvadene, silver sulfadiazine, or gauze containing 0.5% chlorhexidine acetate (110209). Most clinical research shows that applying aloe gel or cream topically up to twice daily reduces healing time when compared with silver sulfadiazine (19771,110210,110212), framycetin (19775), vaseline gauze (19773), or placebo (101,97320) in patients with superficial or partial thickness burns. Topical application of aloe cream up to twice daily might also decrease wound size when compared with silver sulfadiazine and framycetin (19771,19775). In addition, some clinical research in patients with burns caused by sulfur mustard shows that applying cream containing aloe and olive oil twice daily for 6 weeks improves pruritus similarly to betamethasone 0.1% cream and may lead to further reductions in excoriation and fissure (19768). However, some preliminary clinical research shows that applying fresh aloe mucilage or aloe extract daily is no more effective than silver sulfadiazine for reducing wound healing time in patients with superficial or partial thickness burns (19774,19776).
• Constipation. Oral aloe latex may improve symptoms in patients with constipation; however, the U.S. Food and Drug Administration (FDA) has banned the use of aloe latex as a laxative due to safety concerns. Details: Taking aloe latex 100-200 mg daily or aloe extract 50 mg as a stimulant laxative seems to relieve constipation due to the cathartic effects of the anthraquinones in the aloe (4,5,8). Taking 1-3 capsules of a formulation containing aloe 150 mg, celandine 300 mg, and psyllium 50 mg also seems to improve stool consistency and the mean number of stools in patients with chronic constipation when compared with placebo (19747). However, in 2002, the U.S. FDA banned the use of aloe latex for constipation due to safety concerns (8229,8443).
• Diabetes. Oral aloe may reduce blood glucose and glycated hemoglobin (HbA1c) in patients with diabetes. It may be most effective in patients with fasting blood glucose levels of 200 mg/dL or greater. Details: Most clinical research in adults with prediabetes and diabetes shows that taking aloe vera orally can reduce fasting blood glucose by 30-47 mg/dL and HbA1c by 0.41% to 1% (12164,17488,17489,19756,95943,95945,95946). One meta-analysis of 92 patients shows that aloe vera is associated with a larger overall reduction of fasting blood glucose in those with a baseline fasting blood glucose level greater than or equal to 200 mg/dL (95945). Another meta-analysis of 206 patients shows that aloe vera increases high-density lipoprotein (HDL) levels and reduces triglyceride, total cholesterol, and low-density lipoprotein (LDL) levels when compared with placebo in adults with prediabetes and untreated diabetes (95943). These analyses include studies that used multiple forms of aloe vera, including gel powder, extract, raw crushed leaves, and fresh extracted juice, as well as multiple doses ranging from 100-1000 mg of powder and 15-150 mL of juice taken for durations ranging from 4-14 weeks. Significant heterogeneity between studies, small sample sizes, and wide variability in the form and dose of aloe used limit the validity of these findings and the ability to identify an effective dose (95943,95945,95946). Additionally, some research has shown no benefit. This may be due to the different forms and doses of aloe used. One clinical study shows that taking aloe gel as 15 mL twice daily or taking aloe juice 15 mL twice daily does not decrease glucose levels in patients with type 2 diabetes (17420). Other clinical research shows that taking a specific aloe gel complex (Aloe QDM complex, Univera Inc.) containing processed aloe gel 147 mg twice daily for 8 weeks does not affect glycemic indices when compared with placebo in patients with diabetes or prediabetes (90121).
• Genital herpes. Topical aloe extract cream may improve healing of genital herpes lesions. Details: Clinical research in males with genital herpes shows that applying a cream containing aloe extract 0.5% three times daily, 5 days weekly, for up to 2 weeks increases healing rates when compared with aloe gel or placebo. The mean time to healing after application of the aloe extract was 5 days, compared with 12 days with placebo (12164,19745,19746).
• Lichen planus. Rinsing the mouth with aloe-containing mouthwash or applying aloe gel to the mouth or vulva may reduce pain and improve lesion healing in patients with lichen planus. Details: Clinical research in patients with oral lichen planus shows that using 0.4 mL of mouthwash containing aloe gel 70% three times daily for 12 weeks or applying a gel containing aloe mucilage 70% twice daily for 8 weeks is up to 6 times more likely to reduce pain when compared with placebo (19762,19763,19764). However, these findings are questionable due to poor study design. Other clinical research in patients with oral lichen planus shows that using 2 tablespoons of aloe-containing mouthwash four times daily for a month, or applying aloe gel three times daily for 8 weeks, reduces pain and improves lesion healing at least as much as triamcinolone acetonide paste (0.1% in one study) (19765,90130). However, aloe gel may not be as beneficial as laser therapy. A clinical study in patients with lichen planus show that applying a gel containing aloe powder 500 mg to the affected site three times daily for 2 months is less effective for improving pain and lesion healing than receiving low-level laser therapy twice weekly for 2 months. However, no between-group differences were maintained at 7 months after treatment completion (108722). A network meta-analysis of 2 small clinical trials shows that applying aloe trails only purslane of the herbal agents studied with regard to clinical improvement as measured by the Thongprasom scale. However, aloe does not seem to improve complete clinical resolution, clinical scores, or pain (111640). In patients with vulval lichen planus, clinical research shows that topical application with aloe gel twice daily for 8 weeks increases the number of patients who experience clinical improvement of at least 50% when compared with placebo (19766).
• Obesity. Oral aloe gel may modestly reduce body weight and fat mass in adults who are overweight or obese. Details: One clinical trial in overweight and obese adults with diabetes or prediabetes shows that taking a specific aloe gel complex (Aloe QDM complex, Univera Inc.) containing processed aloe gel 147 mg twice daily for 8 weeks reduces body weight by 0.6 kg and fat mass by 1 kg when compared with placebo (90121).
• Oral submucous fibrosis. Topical aloe may reduce burning sensations in patients with oral submucous fibrosis, but it may not improve mouth opening, tongue protrusion, or cheek flexibility in these patients. Details: A meta-analysis of five small clinical studies in patients with oral submucous fibrosis shows that topical application of aloe gel for 3 months reduces burning sensation, possibly for up to two months after treatment, when compared with placebo or active control. A network meta-analysis also found that aloe is most effective in reducing burning sensation, ranked only after treatment with corticosteroids, hyaluronidase, and antioxidants (113514). However, aloe does not seem to improve mouth opening, tongue protrusion, or cheek flexibility (100256). One of the studies included in the analysis used a specific aloe gel (Sheetal lab Surat) 5 mg applied topically on each side of the buccal mucosa three times daily for 3 months (90131). All of the studies included in the analysis were conducted in India, so it is unclear if the results are generalizable to other geographic locations. Limited research has also evaluated the use of topical and oral aloe vera in combination. A small clinical study shows that consuming pure aloe vera juice (Hamant Sai, Sun Vision Company) 30 mL twice daily and applying pure aloe vera gel (Hamant Sai, Sun Vision Company) three times daily for 3 months improves cheek flexibility and tongue protrusion when compared with a treatment regimen consisting of intralesional injections of hydrocortisone acetate 25 mg and hyaluronidase 1500 IU weekly for 6 weeks and supplementation with Cap SM Fibro (Indoco Remedies) twice daily for 3 months. Both treatment regimens show an improvement in mouth opening and burning sensation when compared to baseline, with the aloe vera treatment producing a more rapid improvement in burning sensation (95944). It is not clear how this combination of oral and topical aloe vera compares with topical aloe vera alone.
• Psoriasis. Topical aloe extract cream may reduce erythema and scaling and improve the resolution of psoriatic plaques in patients with psoriasis. Limited research suggests that topical aloe gel does not have the same effects. Details: Applying aloe extract 0.5% cream topically three times daily for 4 weeks significantly improves and increases the resolution of psoriatic plaques when compared with placebo (101,12096,12164). Aloe extract cream also seems to reduce desquamation, erythema, and infiltration (12096). Other preliminary clinical research shows that applying cream containing aloe mucilage 70% twice daily for 8 weeks improves psoriasis severity more effectively than triamcinolone 0.1% cream, although both treatments had similar effects on dermatology-specific quality of life (19741). Treatment with aloe gel does not seem to improve erythema, infiltration, and desquamation associated with psoriasis when compared with placebo (19748).
• Traumatic oral ulcers. Topical aloe gel may prevent oral ulcers after application of orthodontic appliances in adolescents and adults. Details: Clinical research in patients aged 12 years and older shows that applying a gel containing aloe 80% to the gums twice daily for one month after the cementation of orthodontic appliances prevents the development of mouth ulcers when compared with a chlorhexidine gel. Ulcers occurred in about 6% of patients using the aloe gel compared with 81% of those using the chlorhexidine gel. Bleeding and inflammation were also reduced (103305).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alveolar osteitis. It is unclear if topical aloe or the aloe constituent acemannan is beneficial in patients with alveolar osteitis. Details: One small clinical trial in patients with alveolar osteitis shows that applying a patch containing the aloe constituent acemannan (SaliCept patch) to the tooth socket, once after curettage and irrigation and again 3 days later, reduces pain intensity and improves clinical symptoms when compared with curettage and irrigation alone (19754).
• Amenorrhea. Although there has been interest in using oral aloe for amenorrhea, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Anal fissures. It is unclear if topical aloe is beneficial in patients with anal fissures. Details: One small clinical study in patients with chronic anal fissures shows that applying an aloe cream containing 0.5% powdered spray-dried inner aloe leaf juice (Zarban Phyto-Pharmaceutical Co) three times daily for at least 3 weeks, as an adjuvant to sitz baths three times daily, using a laxative, and eating a full fiber diet, improves pain, wound healing, and bleeding severity when compared with placebo (90129).
• Asthma. Although there has been interest in using oral aloe for asthma, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Atopic dermatitis (eczema). Topical aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in patients with atopic dermatitis shows that application of a specific combination cream (Olivederma, Kimi Daru Pharmaceutical Co.) containing aloe gel and virgin olive oil twice daily for 6 weeks improves disease severity and quality of life when compared with betamethasone cream (105020). It is unclear if this effect is due to aloe, olive oil, or the combination.
• Breast engorgement. It is unclear if topical aloe improves lactation-associated breast pain. Details: Meta-analyses of 4-5 clinical trials in lactating patients show that use of topical aloe modestly reduces nipple/breast pain and irritation when compared with no treatment, routine care with topical breast milk or breast massage, or treatment with lanolin (110213). However, studies included in this analysis were not specific to breast engorgement.
• Burning mouth syndrome. It is unclear if topical aloe is beneficial in patients with burning mouth syndrome. Details: One small clinical trial in patients with chronic burning mouth syndrome shows that applying 0.5 mL of aloe 70% gel to sore areas on the tongue three times daily prior to wearing a tongue protector for 12 weeks does not improve pain or symptoms when compared with placebo gel or using the tongue protector alone in patients with chronic burning mouth syndrome (90127). However, differences in baseline pain ratings between study groups limit the validity of these findings.
• Cancer. Oral aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with lung cancer shows that, when administered with standard chemotherapy, three daily doses of 10 mL of a mixture consisting of fresh aloe leaves 300 grams plus honey 500 grams dissolved in 40 mL of alcohol 40% increases the rate of complete response, partial response, or disease control when compared with chemotherapy alone (19752).
• Canker sores. Small clinical studies suggest that applying the aloe constituent acemannan to cancer sores may reduce ulcer size, but not pain. However, the effect of aloe is unclear. Details: Meta-analyses of clinical research show that topical aloe is no more effective than control interventions for reducing the size and pain of oral ulcers (110216). Control interventions have included carrier gel or triamcinolone acetonide 0.1% (19751,110216). However, a recent clinical trial shows that topical aloe gel (G.U.M Canker-X, Sunstar Americas, Schaumburg, USA) after meals and before bedtime for 5 days is more effective than amlexanox 5% paste and placebo for reducing pain and the size of canker sores in patients with recurrent symptoms (110215). Other small clinical trials have investigated the effects of fermented aloe or the aloe constituent acemannan. One small clinical trial in adults with recurrent canker sores shows that applying a fermented aloe gel to oral ulcers three times daily seems to accelerate healing time when compared with chitosan gel (104173). Another small clinical trial in patients with canker sores shows that using a wound dressing containing the aloe constituent acemannan (Carrisyn Gel Wound Dressing) shortens the average healing time of canker sores when compared with an oral analgesic (Orabase-Plain) (19750). Other clinical research shows that applying acemannan 0.5% in Carbopol 934P NF three times daily for 7 days reduces ulcer size, but not pain, when compared with Carbopol 934P NF alone in patients with canker sores (90123). However, applying triamcinolone acetonide 0.1% appears to be more effective in reducing pain and similarly effective in reducing ulcer size when compared with acemannan 0.5% (90123).
• Common cold. Although there has been interest in using oral aloe for the common cold, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Dental plaque. Using aloe-containing toothpaste may reduce dental plaque in adults; however, it is unclear if this is more effective than fluoride-containing toothpaste. Rinsing with an aloe-containing mouthwash may reduce dental plaque in children. Details: One small clinical trial in adults shows that brushing teeth with a dentifrice containing aloe gel (Forever Bright, Forever Living Products) three times daily for 30 days does not reduce the occurrence of plaque better than a fluoridated dentifrice (Sorriso Dentes Brancos, Kolynos do Brasil), although both treatments seem to show improvement when compared to baseline (19755). Another small clinical study in adults with gingivitis shows that using toothpaste containing aloe daily for 24 weeks reduces plaque more effectively than placebo or triclosan-containing toothpaste (19760). In children aged 8-14 years with mild plaque, using a mouth wash containing aloe vera 7% twice daily for 4 weeks reduced plaque by a large amount when compared with placebo. In addition, it was as effective as chlorhexidine 0.2% (103306).
• Depression. Although there has been interest in using oral aloe for depression, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Diabetic foot ulcers. It is unclear whether topical aloe is beneficial for patients with diabetic foot ulcers. Details: One small clinical trial in patients with a stage 1 or 2 diabetic foot ulcer who are receiving oral antibiotics shows that applying a topical product containing aloe and great plantain twice daily for 4 weeks reduces ulcer surface area and time to healing, but not ulcer depth, when compared with antibiotics alone (97323). The effect of applying aloe gel alone without concomitant oral antibiotic therapy is unknown.
• Diaper rash. Topical aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial shows that applying a cream containing aloe gel and olive oil three times daily for 5-10 days reduces diaper rash severity in children less than 3 years of age when compared to baseline; however, it does not seem to be as effective as calendula ointment (19779). The validity of this finding is limited by the lack of a placebo group.
• Dry mouth. It is unclear if rinsing with an aloe-containing mouthwash is beneficial for dry mouth. Details: In patients with dry mouth related to type 2 diabetes, clinical research shows that an aloe vera 50% mouthwash, as 20 mL swished and spit three times daily for 14 days, modestly reduces symptoms of dry mouth when compared with rinsing with a saline control mouthwash (106068). The validity of this study is limited due to unclear reporting.
• Dry skin. Topical aloe or oral aloe sterols may improve some measures of dry skin. However, findings are mixed due to the use of varied formulations and doses. Details: One small clinical trial shows that applying a cream containing freeze-dried aloe extract 0.1% to 0.5% to the skin for 2 weeks increases the amount of water in the stratum corneum, but does not reduce transepidermal water loss, when compared with placebo (19758). Another small clinical study in females with occupational dry skin shows that wearing gloves coated in aloe 8 hours daily for 30 days improves symptoms of dry skin when compared with no treatment (19759). However, it is not clear if the benefits resulted from applying aloe or wearing gloves. One small clinical trial in healthy females shows that consumption of a yogurt containing 500 mg of aloe vera gel powder (0.4 mg of aloe sterol) daily for 12 weeks increases skin hydration, skin elasticity, and collagen content of the dermis while reducing markers of skin fatigue and transepidermal water loss when compared with placebo (95942). However, another study in healthy females shows that taking aloe sterol-enriched aloe extract 0.5 grams daily for 12 weeks does not improve skin hydration when compared with placebo, although redness, itching, collagen content, and transepidermal water loss were improved (101577).
• Epilepsy. Although there has been interest in using oral aloe for epilepsy, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Frostbite. Although there has been interest in using topical aloe for frostbite, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Gingivitis. Using aloe-containing toothpaste may reduce gingivitis in adults, but it does not seem to be more effective than fluoride-containing toothpaste. Rinsing with an aloe-containing mouthwash may reduce gingivitis in children. Details: One small clinical trial in adults shows that brushing teeth with a dentifrice containing aloe gel (Forever Bright, Forever Living Products) three times daily for 30 days does not reduce the occurrence of gingivitis more effectively than a fluoridated dentifrice (Sorriso Dentes Brancos, Kolynos do Brasil), although both treatments seem to show improvement when compared to baseline (19755). Another small clinical study in adults with gingivitis shows that using aloe-containing toothpaste daily for 24 weeks reduces gingivitis more effectively than placebo, but not more than triclosan-containing toothpaste (19760). In children aged 8-14 years with mild gingivitis, using a mouthwash containing aloe vera 7% twice daily for 4 weeks reduced gingivitis by a large amount when compared with placebo. In addition, it was as effective as chlorhexidine 0.2% (103306).
• Heart failure. It is unclear if oral aloe is beneficial in patients with systolic heart failure. Details: A very small clinical study in adults with moderate to moderately severe chronic systolic heart failure shows that taking aloe vera gel capsules 150 mg twice daily for 8 weeks in addition to standard treatment decreases New York Heart Association (NYHA) functional class, improves Minnesota Living with Heart Failure Questionnaire (MLHFQ) total, physical, emotional, and social scores, and enhances sleep quality but does not reduce the severity of obstructive sleep apnea scores or improve six-minute walk test distance when compared with placebo (111663). The study may have been inadequately powered to detect a difference between groups. Additionally, the validity of these effects may be limited by the small sample size.
• Hematopoietic stem cell transplant (HSCT). Oral and topical aloe have only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients undergoing hematopoietic stem cell transplantation shows that treatment with colostrum and aloe orally (Remargin Colostrum Gastro-Gel, Solimè srl, Cavriago, Reggio Emilia, Italy) and as a mouthwash (Remargin Colostrum OS, Solimè srl, Cavriago, Reggio Emilia, Italy) modestly reduces the risk and duration of severe oral mucositis and febrile neutropenia when compared with historical values. There was no effect on the duration of neutropenia, the length of hospital stay, pain, or duration of medications. All patients were also given standard care. The mouthwash was used after each oral hygiene, and the oral treatment was 3 to 5 times daily depending on symptoms (110211).
• Hepatitis. It is unclear if oral aloe is beneficial in patients with hepatitis. Details: One small clinical trial in patients with liver fibrosis primarily caused by hepatitis B or hepatitis C shows that taking a high molecular weight fraction of aloe 0.05 grams three times daily for 12 weeks reduces fibrosis, attenuates liver enzyme activity, and decreases hepatic glutathione content when compared with placebo (19780).
• HIV/AIDS. Small clinical studies suggest that oral aloe or the aloe constituent acemannan may not improve CD4 counts or viral load in patients with HIV. Details: One small clinical trial in patients with HIV shows that taking the aloe constituent, acemannan, 400 mg four times daily does not significantly improve CD4 counts, ratio of CD4 to CD8, or viral load when compared with placebo (19851). Another small clinical study in patients with HIV shows that taking aloe gruel 30-40 mL daily does not improve CD4 counts when compared with those treated with antiretroviral therapy, although both groups show similar increases in weight compared to baseline (19852).
• Hyperlipidemia. Although there has been interest in using oral aloe for hyperlipidemia, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Hypertrophic scars. Topical aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in patients undergoing median sternotomy shows that applying a silicone gel containing aloe extract and other herbal extracts (Bangkok Botanica) to postoperative hypertrophic scars for 6 months reduces the height of the scar and improves pliability by a moderate amount when compared with a silicone placebo gel. There was no effect on pigmentation or vascularity (102793). It is unknown whether any benefit is related to aloe, other ingredients, or their combination.
• Influenza. Oral aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy adults shows that taking a combination supplement containing aloe vera gel, rosemary, and poria mushrooms twice daily 28 days before administering the influenza vaccine and 28 days after vaccination does not improve immunologic markers or reduce symptom severity, symptom duration, frequency of upper respiratory tract infection symptoms, or the use of cold and flu medications when compared with placebo (111921).
• Irritable bowel syndrome (IBS). Small clinical studies suggest that oral aloe extract or juice may not improve symptoms in patients with IBS. Details: Most research suggests that aloe is not effective for improving symptoms of IBS; however, the available evidence is of low-quality, with some studies having high dropout rates or inadequate power to detect significant differences. Two clinical trials show that taking a specific aloe extract (AVH200, Calmino Group AB) 250-500 mg twice daily for 4 weeks does not improve IBS-related symptoms or response rates when compared with placebo (101579,104169), although one of these studies did find a trend toward a higher response rate, defined as a 50% or greater improvement in symptom scores, with aloe over placebo (104169). Also, a pooled analysis of these two studies shows that taking this specific product improves IBS-related pain severity and frequency in patients with diarrhea-prominent IBS (IBS-D) when compared with placebo, but does not seem to improve stool consistency or frequency (108718). Clinical trials evaluating aloe juice 50 mL four times daily for 1 month or 60 mL twice daily for 5 months show no significant improvement in quality of life scores or IBS symptoms when compared with placebo (104170,104171), although one study did find a trend toward improved response in patients with IBS-D (104171). Despite a lack of significant findings in the individual studies, a pooled analysis of the two smallest studies above (104169,104171) shows that aloe extract or juice, taken for 4 weeks, may increase the rate of symptom response by almost 70% when compared with placebo (103307).
• Nipple Fissures. It is unclear if application of an aloe poultice improves nipple-related complications of breastfeeding, such as nipple fissures. Details: A clinical study in females who have just given birth and are breastfeeding for the first time shows that applying a poultice containing aloe gel to the nipples after breastfeeding six times daily for 5 days improves nipple eschar when compared with no treatment. Although there were modest improvements in other outcomes, such as redness, fissures, and epidermolysis, these differences were not significant (108721). Participants were instructed to clean with purified water before the next breastfeeding session.
• Multiple sclerosis (MS). Although there has been interest in using oral aloe for MS, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Oral mucositis. Small clinical studies suggest that oral aloe juice or application of aloe solution inside the mouth may prevent oral mucositis in patients receiving chemotherapy or radiation. Details: Some clinical research shows that drinking 15 mL of juice containing aloe 80% three times daily during radiation therapy decreases the risk of developing moderate or severe mucositis by approximately 39% when compared with placebo (19767,19964). In addition, in children aged 3-6 years undergoing chemotherapy for leukemia, application of a solution containing aloe 70% twice daily inside the mouth, starting three days before chemotherapy, reduces the severity of oral mucositis and delays its onset by 2 weeks when compared with sodium bicarbonate 5% (103304). Other clinical research in adults with head and neck cancer shows that rinsing and then swallowing 20 mL of a solution containing aloe juice 94.5% four times daily throughout the course of radiation therapy does not prevent mucositis when compared with placebo (19963). However, this study was not adequately powered to detect significant differences between study groups. Aloe has also been evaluated in combination with other ingredients for the treatment of oral mucositis. Preliminary clinical research in patients undergoing hematopoietic stem cell transplantation shows that treatment with colostrum and aloe orally (Remargin Colostrum Gastro-Gel, Solimè srl, Cavriago, Reggio Emilia, Italy) and as a mouthwash (Remargin Colostrum OS, Solimè srl, Cavriago, Reggio Emilia, Italy) modestly reduces the risk and duration of severe oral mucositis when compared with historical values. There was no effect on overall risk or time of onset of mucositis. All patients were also given standard care. The mouthwash was used after each oral hygiene, and the oral treatment was 3 to 5 times daily depending on symptoms (110211). Another small clinical study in adults with head and neck cancer receiving radiotherapy shows that rinsing with 5 mL of a mouthwash containing aloe, German chamomile, peppermint oil, and honey 3 times daily for 60 seconds for 6 weeks starting on the first day of radiotherapy reduces oral mucositis incidence, severity, and pain when compared with chlorhexidine and placebo (111291). It is unclear if these findings are due to aloe, other ingredients, or the combination.
• Osteoarthritis. Although there has been interest in using oral and topical aloe for osteoarthritis, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Peptic ulcers. Although there has been interest in using oral aloe for peptic ulcers, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Periodontitis. It is unclear if application of aloe inside the mouth is beneficial for chronic periodontitis. Details: A meta-analysis of small clinical studies in patients with chronic periodontitis shows that using various aloe-containing gels, mouthwashes, and toothpastes improves plaque index when compared with placebo or other treatments (i.e., chlorhexidine rinse, metformin, and tea tree oil). The effect of these aloe products on gingival index could not be determined (108719). The validity of this finding is limited by the variety of aloe formulations and comparators used in the included studies.
• Pressure ulcers. It is unclear if topical aloe is beneficial for the prevention or treatment of pressure ulcers. Details: One small clinical study shows that applying a gel containing the aloe constituent acemannan to pressure ulcers daily for 10 weeks does not reduce the time to healing when compared with management with moist saline gauze (12160,19853). Another small clinical study conducted in Iran in patients with category II pressure ulcers shows that applying topical aloe vera gel after cleaning with normal saline and prior to dressing daily for 15 days reduces pain during dressing changes when compared with normal saline dressing (113672). Other clinical research shows that cleansing wounds with a saline spray containing aloe, silver chloride, and decyl glucoside for 2 weeks improves pressure ulcer healing when compared with isotonic saline spray (19854). It is unclear if this improvement is due to aloe, other ingredients, or the combination in the spray. Aloe has also been evaluated for the prevention of pressure ulcers. A small clinical study in hospitalized patients in an orthopedic ward shows that applying aloe vera gel to the hips, sacrum, and heels twice daily for 10 days reduces pressure ulcer occurrence to 3 of 39 patients, compared to 12 of 38 patients of those receiving placebo (98816). However, methodological limitations with this study, including differences in how the gels were applied, limit the reliability of these results. A clinical study in hospitalized patients receiving intensive care has evaluated either aloe gel 94%, olive oil 100%, or a compounded product containing aloe vera and olive oil in a 3:2 ratio, applied to pressure areas as 10-15 mL every 8 hours. At the end of 30 days, pressure ulcers occurred in 17% of patients receiving the combination product, 20% receiving olive oil, 33% receiving aloe gel, and 37% receiving standard care, suggesting that any benefit may be due to olive oil (108723).
• Radiation dermatitis. There is conflicting evidence about the effectiveness of topical aloe gel for preventing or delaying dermatitis in patients undergoing radiation therapy. These conflicting findings may be due to differences in study designs, products used, and application practices. Details: Two meta-analyses of clinical trials, some of which overlap, in patients with various types of cancer shows that topical aloe does not reduce the incidence or severity of radiation dermatitis (110325,113674) and does not reduce the incidence of erythema, pruritis, moist desquamation, or dry desquamation when compared with control (110325). However, the included studies are limited by a lack of blinding, questionable methodological quality, and a high risk of bias. In contrast, another meta-analysis of generally poor quality randomized controlled trials shows that topical pre-treatment application with aloe as gel, cream, lotion, or fresh plant reduces the risk of radiation dermatitis by 23%, especially mild to moderate radiation dermatitis, when compared with a control group not treated with aloe (110214). One U.S. study included in the analysis shows that applying aloe 98% gel twice daily starting within three days of radiation initiation does not reduce radiation dermatitis when compared with a placebo gel or no treatment (12163). Other research has focused on specific side effects. One clinical trial shows that applying aloe 98% gel three times daily throughout radiation treatment and after treatment does not seem to reduce symptoms of radiation dermatitis in patients being treated for breast cancer (12098). Some research shows that applying aloe 100% gel 6-8 times daily might prolong the time before radiation-related side effects occur, but only when the cumulative dose of radiation is high (>2,700 cGy) (12159). In addition, applying aloe-based gel once daily after radiation treatment is less effective than applying anionic phospholipid-based cream for reducing dryness, erythema, and peeling in children being treated for Hodgkin disease (19855). Aloe has also been evaluated in combination with other ingredients. A small cohort study in patients with head and neck cancer receiving radiation therapy shows that applying aloe 2% and radish 4% gel twice daily until ten days after the last radiotherapy session prevents radiation dermatitis as shown by fewer cases of radiation dermatitis in the 10th, 30th, and 35th radiation sessions when compared with placebo. Furthermore, after the 35th session, the subjects prophylactically treated with the aloe and radish gel had milder grades of radiation dermatitis when compared with control (111662). A preliminary clinical study shows that applying a specific cream product (Radioskin 2, Herbalab di Perazza Massimiliano Company), which contains aloe, ginkgo extract, and metal esculetina, along with another specific cream product (Radioskin 1, Herbalab di Perazza Massimiliano Company), which contains alga atlantica and ethylbisiminomethylguaicolo manganese cloruro, may improve skin hydration and reduce skin toxicity associated with radiation therapy in patients with breast cancer (89727). These creams were applied topically 2-3 times daily at least 3 hours before and after radiation treatment, from 15 days prior to radiation until one month after completion.
• Radiation proctopathy. It is unclear if topical aloe is beneficial for the prevention or treatment of radiation proctopathy. Details: One very small clinical study in females with radiation proctopathy shows that applying 1 gram of an ointment containing aloe vera 3% rectally twice daily in conjunction with taking sulfasalazine 500 mg four times daily for 4 weeks modestly reduces diarrhea, fecal urgency, radiation toxicity, and clinical symptoms when compared with sulfasalazine alone (95941). This same product, applied twice daily for 6 weeks starting on the first day of radiotherapy, has also been evaluated for the prevention of radiation proctopathy. One small clinical study in patients with pelvic cancer shows that applying this ointment prevents proctopathy-related diarrhea, rectal bleeding, and fecal urgency when compared with placebo. Proctopathy-related symptoms occurred in 5% of patients using aloe, compared with 65% of those using placebo. However, there was no difference in rectal pain, constipation, or symptoms of cystitis between groups (101578). A very small clinical study in patients with colorectal cancer shows that applying this ointment prevents proctopathy-related diarrhea and reduces proctopathy severity, but does not improve rectal bleeding, rectal pain, fecal urgency, or symptoms of cystitis, when compared with placebo (108717). Reasons for discrepancies are unclear but might relate to differences in cancer diagnosis and radiation regimens.
• Scabies. It is unclear if topical aloe is beneficial in patients with scabies. Details: One small open-label clinical study in children and adults with scabies shows that application of crude aloe gel for 3 consecutive days, repeated again after one week, may reduce itching and lesions similar to benzyl benzoate lotion in patients with scabies when compared to baseline (19769). The validity of this finding is limited by the lack of a placebo group.
• Seborrheic dermatitis. It is unclear if topical aloe is beneficial in patients with seborrheic dermatitis. Details: One small clinical study in adults with seborrheic dermatitis shows that applying aloe 30% emulsion twice daily for 4-6 weeks reduces scaling, itching, and the number of sites involved, but not erythema, when compared with placebo (19749).
• Stretch marks (striae gravidarum). It is unclear if topical aloe is effective for the prevention or treatment of stretch marks. Details: One small clinical trial in nulliparous patients shows that topical application of a cream containing aloe twice daily, starting at gestational week 16-18, reduces erythema and itching related to abdominal stretch marks, but does not seem to decrease the number of stretch marks, when compared with a base cream (97322). Aloe gel has also been evaluated in combination with fractional carbon dioxide (CO2) laser treatments. A small clinical trial shows that applying a gel containing aloe 87.4% twice daily for up to one month after each of three CO2 laser treatments improves the texture of the skin for up to 6 months after the last laser treatment when compared to baseline. This was as effective as topical recombinant human epidermal growth factor (rhEGF) and CO2 laser treatments. However, when specific sites were examined, only the texture of stretch marks on the buttocks were improved, and these improvements were less than those seen with rhEGF (101580). The effect of aloe for the prevention of stretch marks is unknown.
• Sunburn. Although there has been interest in using topical aloe for sunburn, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Tungiasis. Topical aloe has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study shows that applying a product containing coconut oil, jojoba oil, and aloe leaf extract (Zanzarin, Engelhard Arzneimittel GmbH & Co. KG) to the feet twice daily for one-week intervals seems to reduce the number of embedded sandfleas in individuals with tungiasis when compared with a control group (19778). It is not clear if this effect is due to aloe, the other ingredients, or the combination.
• Ulcerative colitis. It is unclear if oral aloe gel is beneficial in patients with ulcerative colitis. Details: One small clinical trial in patients with mild to moderate ulcerative colitis shows that taking aloe gel for 4 weeks, starting at 25-50 mL twice daily for the first 3 days and increasing to 100 mL twice daily thereafter, reduces symptoms when compared with placebo (11984).
• Vaginitis. It is unclear if topical aloe is beneficial for vaginitis. Details: One small clinical trial in postmenopausal patients with atrophic vaginitis shows that applying 5 mg of a vaginal cream containing aloe gel 2% nightly for 2 weeks, then 3 nights per week for 4 weeks, reduces vaginal dryness, burning, and pain during intercourse and improves measures of vaginal health and maturity when compared to baseline. These effects were similar to those seen with estrogen vaginal cream (104175).
• Varicose veins. Although there has been interest in using oral and topical aloe for varicose veins, there is insufficient reliable information about the clinical effects of aloe for this purpose.
• Wound healing. There is conflicting evidence about the effectiveness of topical aloe products for improving wound healing. These conflicting findings may be due to differences in study designs, products used, and application practices. Details: One small clinical study shows that applying aloe gel to a caesarean wound after surgery, followed by a dry gauze, improves wound healing over the first 24 hours when compared with the dry gauze alone (90128). However, other clinical research in a small number of patients undergoing gynecologic surgery or cesarean section shows that applying an aloe gel extract (Carrington Dermal Wound Gel) to surgical wounds may actually delay wound healing (11982). Another small clinical trial shows that applying a formulation of aloe gel 0.5% cream (Zarband, Phytopharmaceutical Co.) to hemorrhoidectomy wounds three times daily for 4 weeks improves healing rates and pain relief scores and decreases intake of narcotic analgesics when compared with placebo (17418). However, another clinical trial in patients with biopsy wounds shows that application of a hydrogel containing the aloe constituent, acemannan (Carrasyn, Carrington hydrogel), does not improve wound epithelialization, wound infections, or pain when compared with conventional therapy (19856). Additionally, there is contradictory evidence about the effectiveness of aloe for improving skin graft donor site healing. One small clinical study shows that applying aloe gel 87.4% daily to split-thickness skin graft donor sites reduces time to complete healing by about 2 days when compared with placebo (97320). However, another small clinical study shows that applying aloe cream three times daily to split-thickness skin graft donor sites does not improve healing time when compared with placebo (97321).
• Wrinkled skin. Although there has been interest in using topical aloe for wrinkled skin, there is insufficient reliable information about the clinical effects of aloe for this purpose. More evidence is needed to rate aloe for these uses.

(Read more about ALOE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Constipation. Although there has been interest in using oral dandelion for constipation, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Dyspepsia. Although there has been interest in using oral dandelion for dyspepsia, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Flatulence. Although there has been interest in using oral dandelion for flatulence, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Heart failure. Although there has been interest in using oral dandelion for its diuretic effects in patients with heart failure, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Joint pain. Although there has been interest in using oral or topical dandelion for joint pain, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Postoperative pain. It is unclear if topical dandelion is beneficial in patients with pain after jaw surgery. Details: A small clinical study in patients undergoing maxillofacial surgery shows that topical application of dandelion combined with borneol one time on the day of surgery and twice daily on the first and second days after surgery for 30 minutes does not reduce maxillofacial pain when compared with cold compresses or either ingredient alone (112484). The validity of this finding is limited by concurrent use of opioid analgesic and nonsteroidal anti-inflammatory medications.
• Postoperative swelling. It is unclear if topical dandelion is beneficial in patients with swelling after jaw surgery. Details: A small clinical study in patients who underwent maxillofacial surgery shows that topical application of dandelion combined with borneol one time on the day of surgery and twice daily on the first and second days after surgery for 30 minutes modestly reduces facial swelling and improves mouth opening abilities when compared with cold compresses or borneol alone (112484). It is unclear whether this effect is due to dandelion, borneol, or the combination.
• Tonsillitis. It is unclear if oral dandelion is beneficial in patients with tonsillitis. Details: One small clinical study in patients with acute purulent tonsillitis shows that eating soup containing dandelion (pugongying soup) daily for 3 days along with benzylpenicillin sodium 640,000 units daily improves recovery when compared with placebo plus benzylpenicillin sodium. Recovery rates were 36% with the dandelion-containing soup compared to 10% with placebo (18292).
• Urinary tract infections (UTIs). Oral dandelion has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in females with recurrent UTIs shows that taking a specific combination of dandelion root and uva ursi leaf extracts three times daily for 1 month reduces the risk of UTI recurrence when compared with placebo at 12-month's follow-up. For every 5 patients treated with this combination over placebo, one additional UTI was prevented (1932). In this combination, uva ursi is used for its antibacterial properties and dandelion is used to increase urination. However, this combination is not recommended for extended use because uva ursi may be unsafe when used long-term. Another small clinical study in premenopausal females with acute, uncomplicated lower UTIs shows that taking a combination product containing dandelion extract 50 mg, D-mannose, prebiotics, arabinogalactan, and astragalus root extract twice daily for five days, along with phenazopyridine and alkylating agents as conventional therapy, improves UTI symptoms and bacteriuria when compared with placebo plus conventional therapy (111757). It is unclear if these effects are due to dandelion, other ingredients, or the combination. More evidence is needed to rate dandelion for these uses.

(Read more about DANDELION)

POSSIBLY EFFECTIVE

• Burns. Topical gotu kola seems to improve the rate of burn healing. Details: Clinical research shows that applying a cream containing gotu kola 3% once daily to second degree burns increases the rate of re-epithelialization and complete healing by about 7 days when compared with silver sulfadiazine (SSD) 1% cream. Gotu kola cream also seems to reduce dryness, itching, irritation, and scar severity when compared with SSD (97027). Other research in adults with second degree burns shows that applying a gauze dressing containing gotu kola 5% and aloe 2.5%, covered with absorbent cotton wool and changed every 3 days, reduces time to healing by 1.5 days and length of hospital stay by 1.7 days when compared with the use of a gauze dressing containing chlorhexidine acetate 0.5% (97028).
• Venous insufficiency. Oral gotu kola seems to improve symptoms of venous insufficiency. Details: Clinical research shows that taking gotu kola or a specific extract of gotu kola (Centellase) 60-180 mg daily orally for 4-8 weeks seems to improve measures of circulation and decrease symptoms such as edema in patients with venous insufficiency (6887,9786,11063,11064,11066,11070,52894,52909).

POSSIBLY INEFFECTIVE

• Cognitive function. Oral gotu kola does not seem to be beneficial for cognitive function. Details: A meta-analysis of a small number of generally moderate quality clinical trials shows that taking a single dose of gotu kola, alone or in combination with other ingredients, does not improve cognitive function when compared with placebo (105334). In one study, gotu kola was taken in combination with ginkgo and docosahexaenoic acid (DHA) for 4 months by healthy, cognitively intact older adults (52880).
• Radiation dermatitis. Topical gotu kola does not seem to reduce symptoms of radiation dermatitis. Details: Clinical research in females undergoing radiotherapy for breast cancer shows that applying a cream containing gotu kola extract 7% once daily during and up to 4 weeks following radiotherapy does not reduce the severity of dermatitis when compared with no treatment or applying a moisturizing cream (102792).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Oral gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy, middle-aged females shows that applying a topical emulsion containing extracts of gotu kola 3% and Indian gooseberry 3% twice daily for 60 days improves skin hydration, some measures of skin wrinkles, and elasticity of the cheek (but not the eye) when compared with placebo (111571). It is unclear if these effects are due to gotu kola, Indian gooseberry, or the combination.
• Alzheimer disease. Although there is interest in using oral gotu kola for Alzheimer disease, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Anal fissures. It is unclear if topical gotu kola is beneficial for anal fissures. Details: In patients with chronic anal fissures who are using standard dietary and hygiene treatments, preliminary clinical research shows that taking gotu kola extract 60 mg twice daily for 8 weeks and locally applying an ointment containing gotu kola does not reduce the mean time to bleeding cessation when compared with standard treatments alone. However, pain may be modestly improved. Also, gotu kola was less effective than an unspecified flavonoid mixture used both orally and topically (105332).
• Atherosclerosis. It is unclear if oral gotu kola is beneficial for slowing the progression of atherosclerotic plaques. Details: Some preliminary clinical research shows that taking gotu kola extract 60 mg orally three times daily for 12 months helps stabilize low-density atherosclerotic plaques when compared with placebo (11062,11069). Gotu kola has also been evaluated in combination with a specific maritime pine bark product (Pycnogenol, Horphag Research). A non-randomized clinical trial shows that taking gotu kola 225 mg and Pycnogenol 150 mg in two divided doses daily for 3 months reduces plaque height and length and increases plaque echogenicity and stability when compared to control (97030). Another non-randomized clinical study in adults with atherosclerotic plaques and no other cardiovascular risk factors shows that taking gotu kola extract 100 mg and Pycnogenol 100 mg daily for up to 4 years reduces plaque progression and increases plaque echogenicity when compared with Pycnogenol alone or no treatment at all. Taking gotu kola and Pycnogenol is also associated with a reduced rate of clinical vascular events, including angina, myocardial infarction, minor transient ischemic attacks (TIAs), and minor strokes when compared with taking Pycnogenol alone or receiving no treatment at all (97029). It is unclear how these outcomes would compare to the use of gotu kola alone.
• Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral gotu kola for ADHD, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Atopic dermatitis (eczema). Topical gotu kola 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 5% each of the extracts of heart's ease, gotu kola, and Oregon grape twice daily for 4 weeks does not improve eczema when compared with a base cream. However, patients with eczema on skin exposed to cold weather might experience some improvement (67372).
• Depression. Although there is interest in using oral gotu kola for depression, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Diabetic foot ulcers. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with deep diabetic foot ulcers, preliminary clinical research shows that applying a cream (WH-1 cream) containing 1.25% of gotu kola and Plectranthus amboinicus extracts in a 4:1 ratio twice daily for 2 weeks after surgical debridement is as effective as the use of a standard hydrocolloid fiber wound dressing for improving wound size. However, when compared with baseline, changes in wound size were not statistically significant (105335).
• Diabetic microangiopathy. It is unclear if oral gotu kola is beneficial for diabetic microangiopathy. Details: Preliminary clinical research shows that taking gotu kola extract 60 mg orally twice daily for 6-12 months helps increase measures of circulation and decrease edema in patients with diabetic microangiopathy (11065,11068,52917).
• Dry skin. It is unclear if topical gotu kola is beneficial for dry skin. Details: In patients with dry skin associated with type 2 diabetes, clinical research shows that topical application with 0.25 grams of a gotu kola 1% ointment twice daily, either alone or with oral gotu kola 1100 mg twice daily, for 28 days does not improve dry skin when compared with placebo. However, in a sub-group of patients with well-controlled diabetes, the combination of oral and topical gotu kola modestly improved dry skin (105329). Additionally, a small clinical study in individuals with dry skin due to working with synthetic and natural dyes shows that application of a gotu kola 2% ceramide-based cream to the hands and arms twice daily for 4 weeks improves skin barrier hydration, as measured by hydration of the stratum corneum and skin acidity, when compared to baseline. These improvements were similar to those seen with a ceramide 5% cream (109554). As the gotu kola cream was formulated with ceramide, it is unclear if these findings are due to gotu kola, ceramide, or the combination.
• Epilepsy. Although there is interest in using oral gotu kola for epilepsy, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Generalized anxiety disorder (GAD). It is unclear if oral gotu kola is beneficial for GAD. Details: In patients with GAD, preliminary clinical research shows that taking gotu kola extract 500 mg twice daily for 60 days reduces symptoms of anxiety, depression, and stress by 22% to 26% when compared with baseline (105333). The validity of these findings is limited by the lack of a comparator group.
• Hemorrhoids. It is unclear if topical gotu kola is beneficial for hemorrhoids. Details: Preliminary clinical research in patients with chronic hemorrhoids, as well as patients with acute symptoms following a hemorrhoidectomy or surgical treatment for hemorrhoidal thrombosis, shows that taking gotu kola extract (Centella complex) 60 mg twice daily for 15 weeks and locally applying an ointment (Proctocella) containing gotu kola, arnica, and aloe, in conjunction with standard treatments, does not reduce the mean time to bleeding cessation when compared with standard treatments alone. Anal irritation was modestly improved in the patients with chronic hemorrhoids and in those undergoing treatment for hemorrhoidal thrombosis, but not in those that had undergone a hemorrhoidectomy (105336).
• Herpes zoster (shingles). Although there is interest in using oral gotu kola for shingles, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Hypertension. It is unclear if oral gotu kola is beneficial for hypertension. Details: Preliminary clinical research in patients with hypertension shows that drinking a tea made by boiling gotu kola 4 grams in 250 mL water three times daily for 3 days modestly reduces systolic and diastolic blood pressure when compared with baseline. After consuming the tea, about 40% of patients had normal or high-normal systolic blood pressure and 77% had optimal or normal diastolic blood pressure, compared with 0% and 45%, respectively, prior to consumption (105330). The validity of these findings is limited by the lack of a comparator group.
• Hypertrophic scars. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that topical use of a specific silicone gel (Bangkok Botanica) containing 15% extracts of gotu kola, onion, aloe, and paper mulberry, starting 2 weeks after surgery and continuing for 6 months, moderately improves the height and pliability of the post-surgical hypertrophic scar when compared with a silicone placebo gel. There was no effect on pigmentation or vascularity (102793). It is unknown whether any benefit is related to gotu kola, other ingredients, or their combination.
• Idiopathic interstitial pneumonia. Oral gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small observational registry study in males less than 65 years old with idiopathic interstitial pneumonia has found that taking a specific gotu kola extract (Centellicum; Horphag Research) 225 mg three times daily in combination with a standardized extract of maritime pine bark (Pycnogenol, Horphag Research) 50 mg three times daily for 8 months is associated with a modest improvement in Karnofsky Performance Scale scores and a reduction in fatigue when compared with pirfenidone (108862). However, the validity of these findings is limited by the unblinded, non-randomized nature of the study.
• Keloids. It is unclear if oral or topical gotu kola are beneficial for keloids. Details: There is some early evidence that applying a specific extract of gotu kola (Madecassol) topically might help reduce keloids and hypertrophic scarring (13558). Gotu kola has also been taken orally for keloids. Preliminary clinical research in patients at high risk for keloids shows that taking a specific extract of gotu kola (Centellicum, Horphag Research Ltd) 450 mg daily for 4 weeks starting on the second week after surgery seems to improve scar homogeneity and regularity (99756). However, the reliability of these results is limited because patients in this study were not randomized or blinded to different interventions.
• Laser skin resurfacing. It is unclear if topical gotu kola is beneficial for recovery from laser skin resurfacing. Details: A small clinical trial shows that applying a gel containing gotu kola extract (ECa 233) 0.05% four times daily for 7 days, then twice daily for 3 months, improves wound healing following laser resurfacing for facial acne. Redness returned to baseline levels by day 7, in contrast to day 28 on the side treated with a placebo gel. The general wound appearance and crusting were also improved on the side on which the gotu kola extract gel was applied (102794).
• Osteoarthritis. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large, single-blind clinical study in adults with knee osteoarthritis causing moderate pain shows that applying a specific cream (TMP-4) containing extracts of gotu kola leaf, sesame seed, soybean, and mangosteen peel four times daily for 4 weeks provides similar improvement in pain scores when compared with diclofenac 1% gel. Topical TMP-4 cream also seems to improve knee stiffness, stair climbing, and mobility similarly to diclofenac gel. However, patient impression of overall improvement was higher with diclofenac (110128). The validity of this study is limited by inadequate blinding.
• Scarring. It is unclear if topical gotu kola is beneficial for scarring or tenderness from scarring. Details: Preliminary clinical research in patients without a history of keloid formation suggests that applying a specific cream (Alpha Centella, not available in the US) containing gotu kola and Bulbine frutescens extracts twice daily for 6-8 weeks following suture removal might help to reduce scarring (11072). Also, a large clinical study in adults who underwent carpal tunnel release surgery shows that applying gotu kola cream 1% three times daily for 6 months after suture removal marginally improves self-reported scar tenderness pain when compared with control, and modestly improves scarring scores when compared to baseline (112425). However, the interpretation of these findings is limited by patient-reported outcomes and insufficient validity of the scar scoring tool in this population.
• Skin grafts. Although there is interest in using topical gotu kola for skin graft recovery, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Stretch marks (striae gravidarum). It is unclear if oral gotu kola is beneficial for stretch marks; topical gotu kola has only been evaluated in combination with other ingredients. Details: Preliminary clinical research in females with stretch marks shows that taking a specific extract of gotu kola (Centellicum, Horphag Research Ltd) 225 mg three times daily for 6 weeks increases skin thickness, elasticity, and perfusion when compared with a stretch mark minimizer cream (Clarins) and regular control cream (99757). The validity of these results is limited by the fact that patients were not randomized or blinded to the different interventions. Gotu kola has also been evaluated topically in combination with other ingredients. Preliminary clinical research shows that applying a specific mixture of gotu kola, vitamin E, and collagen-elastin hydrolysates in a cream (Trofolastin, not available in the US) daily during the second and third trimesters reduces stretch marks when compared with a placebo cream (13559). Another small clinical study shows that applying a specific mixture of gotu kola, vitamin E, essential fatty acids, hyaluronic acid, elastin, and menthol in an ointment (Verum, not available in the US) helps decrease the formation of stretch marks during pregnancy when compared with placebo (11073). Other preliminary clinical research in patients without previous striae shows that applying a specific formula containing hydroxyprolisilane C, rosehip oil, gotu kola triterpenes, and vitamin E (Velastisa Antiestrías, ISDIN) twice daily, beginning at week 10-14 and continuing throughout pregnancy, decreases the severity of both new and old stretch marks and the incidence of stretch marks when compared with placebo (92507). It is unclear if the effects seen in these studies are due to gotu kola, other ingredients, or the combinations.
• Systemic lupus erythematosus (SLE). Although there is interest in using oral gotu kola for SLE, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Tonsillitis. Although there is interest in using oral gotu kola for tonsillitis, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
• Venous thromboembolism (VTE). It is unclear if oral gotu kola is beneficial for VTE prevention. Details: Preliminary clinical research shows that gotu kola decreases edema and improves measures of circulation in patients traveling on airplanes for more than 3 hours when compared to a control group receiving no treatment (11067). However, it is unknown if these changes reduce the incidence of clots.
• Wound healing. Although there is interest in using topical gotu kola for wound healing, there is insufficient reliable information about the clinical effects of gotu kola for this purpose.
• Wrinkled skin. It is unclear if topical gotu kola is beneficial for wrinkled skin. Details: Small, low-quality studies in healthy adults suggest that topical formulations of gotu kola extract or the constituent asiaticoside 0.1% or 0.2% applied 1-3 times daily have shown modest benefit for wrinkled skin. Cream or gel formulations were used for 12 weeks for periorbital wrinkles and a lipstick was used for 8 weeks for lip wrinkles. However, the extent of benefit is not clear and meta-analyses are limited to a very small number of studies with varied comparator groups, including placebo, vehicle, tretinoin 0.02%, and Pueraria mirifica extract (106639). More evidence is needed to rate gotu kola for these uses.

(Read more about GOTU KOLA)

POSSIBLY EFFECTIVE

• Antibiotic-associated diarrhea. Most research shows that oral Lactobacillus acidophilus, alone or in combination with other probiotics, seems to reduce the risk of antibiotic-associated diarrhea (AAD) in adults. Details: A meta-analysis of 18 clinical trials in hospitalized or outpatient adults shows that taking L. acidophilus alone or in combination with up to 8 other probiotic strains reduces the risk of AAD by 34% when compared with taking placebo (107635). One small clinical trial in elderly adults shows that AAD occurred in 17% of those taking L. acidophilus (Florajen Acidophilus) 20 billion colony-forming units (CFUs) three times daily, compared with 37% of those taking placebo (95400). A number of combination products have also demonstrated benefit for preventing AAD, including Bio-K+ Cl1285 which provides L. acidophilus CL1285, Lacticaseibacillus casei LBC80R, and Lacticaseibacillus rhamnosus CLR2 as 100 billion CFUs daily (25494,95402,95403); L. acidophilus and Bifidobacterium animalis subsp. lactis (90239); and Ecologic AAD which provides L. acidophilus NIZO 3678 and NIZO 3887, Lacticaseibacillus paracasei NIZO 3672, Lactiplantibacillus plantarum NIZO 3684, L. rhamnosus NIZO 3689, Ligilactobacillus salivarius NIZO 3675, Bifidobacterium bifidum NIZO 3804, Bifidobacterium animalis subsp. lactis NIZO 3680, and Enterococcus faecium NIZO 3886 (95405). However, some combination products have not demonstrated benefit. Clinical research shows that taking a combination of L. acidophilus and bifidobacteria or a combination of L. acidophilus and Lactobacillus delbrueckii subsp. bulgaricus (Lactinex) is not beneficial (90231,90239,92255,95385). An additional large clinical trial in children aged 3 months and up shows that taking L. acidophilus in combination with other probiotics does not reduce the risk of antibiotic-associated diarrhea when compared with taking placebo, when the more stringent definition is considered excluding diarrhea of other etiologies. However, the risk of diarrhea of any etiology is reduced by 35%. The probiotic supplement provided a total of 10 billion CFUs of L. acidophilus W37, Bifidobacterium bifidum W23, Bifidobacterium animalis subsp. lactis W51, Lactobacillus acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, Lacticaseibacillus rhamnosus W71, and Ligilactobacillus salivarius W24 daily from the first day of antibiotic treatment until 7 days after treatment ended (110969).
• Bacterial vaginosis. Most clinical research shows that intravaginal application of Lactobacillus acidophilus may be helpful for the treatment of bacterial vaginosis. It is unclear if oral L. acidophilus is beneficial for the treatment or prevention of bacterial vaginosis. Details: One clinical trial shows that intravaginal suppositories containing 100 million to 1 billion colony-forming units (CFUs) of L. acidophilus (Vivag, Pharma Vinci A/S) given twice daily for 6 days improve bacterial vaginosis resolution rates when compared with placebo (13177). Another clinical trial shows that using 1-2 vaginal tablets containing viable L. acidophilus 10 million CFUs and estriol 0.03 mg per tablet (Gynoflor, Medinova) daily for 6 days increases cure rates when compared with placebo (13176). However, using this product in combination with metronidazole 400 mg twice daily for 7 days does not improve outcomes when compared with metronidazole alone (90237). Preliminary clinical research in patients with clinically defined bacterial vaginosis shows that daily intravaginal application with a douche providing L. acidophilus 1 billion CFUs per mL for 6 days might have beneficial effects on the vaginal flora. When compared with 52.5% of patients with bacterial vaginosis based on bacterial flora at baseline, 7.5% met this criteria 14 days after treatment had been completed (111788). Oral L. acidophilus has also been evaluated. Preliminary clinical research shows that eating yogurt 125 mL daily enriched with L. acidophilus for 2 months might slightly decrease the incidence of recurrent bacterial vaginosis (1245). L. acidophilus has also been investigated in an oral formulation in combination with other probiotics. Clinical research in patients with bacterial vaginosis cured within the past 48 hours shows that taking a product containing L. acidophilus in combination with other probiotics results in recurrence of vaginosis in 18.3% of patients, a statistically significant reduction compared with 32.1% of those using placebo. The mean time to recurrence was approximately 23 days longer in patients taking the lactobacilli. The product contained L. acidophilus 1.08 billion CFUs along with Lactobacillus crispatus LMG S-29995 and Levilactobacillus brevis (Lactogyn, Vésale Pharma, Belgium), and was taken twice daily for 7 days and then once daily for up to an additional 120 days (110950).
• Helicobacter pylori. Oral Lactobacillus acidophilus, usually in combination with other probiotics, seems to improve H. pylori eradication when used along with standard therapies. It is unclear if heat-killed L. acidophilus is beneficial for H. pylori eradication. Details: A meta-analysis of clinical studies utilizing probiotic products containing L. acidophilus shows that these products can improve H. pylori eradication rates 1.14- to 1.24-fold when taken in combination with triple therapy consisting of a proton-pump inhibitor (PPI), clarithromycin, and amoxicillin. Based on these results, about 7-11 patients would need to be treated in order for one additional patient to achieve complete remission (95394). Only one of the trials in this analysis investigated L. acidophilus alone; an additional 8 used L. acidophilus in combination with other probiotics. Individual clinical trials have shown that a combination of L. acidophilus, Enterococcus faecalis, and Bacillus subtilis 30 million colony-forming units (CFUs) total, taken in three divided doses daily, from 2 weeks prior tol 2 weeks after triple therapy increases H. pylori eradication when compared with triple therapy alone (90248). In children, a combination of L. acidophilus (strain 5) 94 million CFUs and Bifidobacterium bifidum (strain 12) 8.6 million CFUs in combination with a PPI, clarithromycin, and amoxicillin or metronidazole has been used daily for 2 weeks, followed by the probiotics alone for an additional 4 weeks (90602). However, other individual clinical trials have shown that L. acidophilus in combination with Lacticaseibacillus rhamnosus, Bifidobacterium bifidum, and Streptococcus faecium may not improve eradication rates when taken with triple therapy consisting of furazolidone, tetracycline, and lansoprazole (90279). Also, taking L. acidophilus along with six other probiotics in conjunction with bismuth quadruple therapy does not seem to improve H. pylori eradication rates when compared with placebo and bismuth quadruple therapy (90291). Also, taking L. acidophilus and L. casei without any standard H. pylori therapy does not improve H. pylori eradication rates in adults (12766). Heat-killed L. acidophilus has also been investigated in adults with H. pylori. Taking a lyophilized and inactivated culture of L. acidophilus (Lacteol Fort) containing 5 billion cells, 3 times daily for 10 days, modestly increases the eradication rate in patients using triple therapy of rabeprazole, clarithromycin, and amoxicillin for 7 days (8562).
• Irritable bowel syndrome (IBS). Some research shows that oral live Lactobacillus acidophilus, taken alone or in combination with other probiotics, may be beneficial for IBS. The effects of non-viable, heat-killed L. acidophilus are unclear. Details: Clinical research in adults with IBS shows that taking L. acidophilus DDS-1 10 billion colony-forming units (CFUs) daily for 6 weeks modestly reduces the severity of abdominal pain when compared with placebo. Also, 52% of patients experienced a more than 30% reduction in pain severity, compared with 16% of those taking placebo. There were also improvements in abdominal distention and duration of pain; however, there were no changes in bowel habits (107581). A meta-analysis shows that taking L. acidophilus improves the rate of symptom relief and reduces bloating severity when compared with placebo. However, other symptoms were not improved (110866). L. acidophilus has also been examined in combination with other probiotics. One clinical study shows that taking a specific combination product (Visbiome, ExeGi Pharma) containing L. acidophilus and 7 other species as 450 billion CFUs daily in two divided doses for 8 weeks improves abdominal bloating, but not abdominal pain, flatulence, or number of stools, in patients with diarrhea-predominant IBS (IBS-D) (11379). Another clinical study in patients with IBS-D shows that taking a specific multi-species probiotic (NordBiotic, MBM Biotix) containing L. acidophilus LA120, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, Lacticaseibacillus casei LC130, Lactiplantibacillus plantarum LP140, Bifidobacterium breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium animalis subsp. lactis BL040, and Streptococcus thermophilus ST250 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life, when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516). A small clinical trial shows that taking L. acidophilus NCFM plus Lactobacillus helveticus Lafti L10 (Lallemand Health Solutions) 5 billion CFUs each daily for 8 weeks modestly reduces flatus and overall symptoms, but not abdominal pain or bloating, when compared with taking placebo (111785). However, other probiotic compounds containing L. acidophilus have not demonstrated benefit in most patients with IBS. These include L. acidophilus NCFM 10 billion CFUs daily for 12 weeks; L. acidophilus, L. paracasei, and Bifidobacterium animalis subsp. lactis BB-12 (Cultura) 13-20 billion CFUs daily for 6 months; or L. acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2 50 billion CFUs each daily for 3 months (90236,94696,94697,95365,99789). Further research is needed to determine which IBS subtype, if any, is most likely to benefit. Heat-killed L. acidophilus has also been investigated in patients with IBS. One clinical study shows that taking capsules containing heat-killed L. acidophilus (Lacteol Fort) 20 billion colony-forming units (CFUs) daily for 6 weeks improves abdominal pain, bloating, and number and quality of stools when compared with placebo (7744). Also, in patients with IBS-D, observational research has found that use of heat-killed L. acidophilus (Lacteol LB) two capsules daily for one month modestly reduces pain and bloating and improves quality of life. The average weekly number of stools decreased by approximately 4.75. Also, the number of patients with watery stools was reduced from 54% at baseline to 19% (107535).

POSSIBLY INEFFECTIVE

• Atopic disease. Oral Lactobacillus acidophilus does not seem to be beneficial for preventing atopic disease in children. Details: A meta-analysis of clinical research shows that administering L. acidophilus during pregnancy, when breastfeeding, or to newborn infants might actually increase the risk of atopic sensitization (90251). However, the number of studies included in this analysis was limited.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A preliminary clinical study shows that taking a specific probiotic product containing L. acidophilus 5 billion colony-forming units (CFUs), Lactobacillus delbrueckii subsp. bulgaricus 5 billion CFUs, and Bifidobacterium bifidum 20 billion CFUs (Trenev Trio/Healthy Trinity, Natren) twice daily along with minocycline once every evening for 12 weeks improves inflamed and non-inflamed acne lesions in 82% of patients, compared to only 67% of patients treated with either the probiotic combination or minocycline alone (90270).
• Acute respiratory distress syndrome (ARDS). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in premature infants shows that taking 6 billion CFUs of a combination of L. acidophilus NCDO 1748 and Bifidobacterium bifidum NCDO 2203 (UFC Inforan, Switzerland) from 7 days of age until 34 weeks postmenstrual age or discharge does not reduce the odds of ARDS when compared with a control group of infants not given these probiotics. The infants in this study were born at less than 32 weeks gestation and had a birthweight of less than 1500 grams (111794). This study is limited by the lack of randomization to treatment group; placement was based on year of birth.
• Allergic rhinitis (hay fever). It is unclear if oral Lactobacillus acidophilus is beneficial for allergic rhinitis prevention or treatment. Details: A small clinical trial in patients with perennial allergic rhinitis shows that taking heat-treated milk fermented with L. acidophilus L-92 100 mL daily for 8 weeks modestly reduces nasal symptoms and mucus, but not ocular symptoms, when compared with taking an acidified placebo milk. The milk provided approximately 30 billion L. acidophilus cells (25488). The effect of L. acidophilus as a probiotic is unclear from this study. Other clinical research shows that drinking 250 mL of fermented milk containing L. acidophilus La-5 5 billion colony-forming units (CFUs), Lacticaseibacillus rhamnosus GG 50 billion CFUs, and Bifidobacterium animalis subsp. lactis BB-12 50 billion CFUs from 36 weeks' gestation until 3 months postpartum does not reduce the incidence of allergic rhinitis in the child at 6 years of age when compared with placebo milk (96893).
• Asthma. It is unclear if oral Lactobacillus acidophilus can improve lung function in people with asthma. Details: A small clinical crossover study in patients with moderate asthma shows that consuming live active yogurt 225 grams, providing L. acidophilus 760 million colony-forming units (CFUs) per gram, twice daily for 1 month does not affect measures of lung function when compared with yogurt not containing L. acidophilus. All yogurt contained Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus (1244).
• Atopic dermatitis (eczema). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of the available clinical research shows that intake of lactobacilli and bifidobacteria-based probiotics during gestation, followed by giving the probiotic to the newborn for the first 2-6 months of life, reduces the risk of developing atopic dermatitis by 40% over the next 6-24 months when compared with placebo, regardless of family history of atopy. However, only four of 10 studies included in the analysis used L. acidophilus as part of the probiotic combination; the results from these individual, small studies support the overall findings of the meta-analysis (107503). Some clinical research also shows that supplementation with 250 mL of fermented milk containing L. acidophilus La-5, Lacticaseibacillus rhamnosus GG, and Bifidobacterium animalis subsp. lactis BB-12 starting at 36 weeks' gestation and continuing until 3 months' postpartum, without supplementation in the infant, reduces the overall occurrence of atopic dermatitis in the child at 2 years of age. However, at 6 years of age, the effect appears to be inconclusive (96893). In children ages 1-3 years with moderate to severe atopic dermatitis, taking 5 billion colony-forming units (CFUs) of a combination of L. acidophilus DDS-1 and Bifidobacterium animalis subsp. lactis UABLA-12 along with fructo-oligosaccharides (FOS) (DDS Junior) twice daily for 8 weeks modestly reduces symptom severity and the need for topical corticosteroids when compared with placebo (110995).
• Bronchopulmonary dysplasia. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One large observational study in premature infants suggests that taking L. acidophilus 1 to 3 billion CFUs with Bifidobacterium longum subsp. infantis during the first month of life for the prevention of necrotizing enterocolitis was not associated with a reduced risk of bronchopulmonary dysplasia. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Cancer. Although there has been interest in using oral Lactobacillus acidophilus for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• Canker sores. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A systematic review and meta-analysis of mainly small and preliminary clinical trials shows that taking lactobacilli probiotics has a small effect on pain from canker sores. However, the dose and duration of probiotic and the specific species, as well as endpoints and results from individual studies, are mixed. One small study shows that taking a combination of L. acidophilus, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, and Bifidobacterium animalis subsp. lactis reduces pain, but not the number of lesions or healing time, when compared with placebo. Another study shows that using lozenges providing inulin 0.13 gram along with L. acidophilus and B. animalis subsp. lactis 1.5 billion colony-forming units each reduces pain, but does not affect ulcer size or healing, when compared with Oracure gel (105146). Many of the individual studies may have been underpowered to detect a difference between groups.
• Cholestasis. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in premature infants shows that the risk of developing cholestasis is reduced from 22% to 6% in those given a blend of L. acidophilus, bifidobacteria, and Enterococcus faecalis (Peifeikang powder, Shanghai Xinyi Pharmaceutical Company) at least 5 million colony-forming units three times daily, from birth until implementation of total parenteral nutrition, when compared with infants not given this powder. In the infants that developed cholestasis, the severity was reduced, resulting in a reduction in the rate of cholestatic liver injury, feeding intolerance, and necrotizing enterocolitis. The number of days to reach full enteral feeding, days to normal weight gain, and days of hospitalization were reduced by approximately 2.8, 2.1, and 1.7 days, respectively (103448).
• Clostridioides difficile infection. It is unclear if oral Lactobacillus acidophilus is beneficial for preventing C. difficile occurrence or recurrence. Details: Current guidelines from the Infectious Diseases Society of America (IDSA) state that there is insufficient information to recommend administration of probiotics for the primary prevention of C. difficile-associated diarrhea (107538). Evidence from clinical and observational research investigating the effect of L. acidophilus on C. difficile occurrence or recurrence is weak. Most studies use this species in combination with one or more additional probiotic species, including as Bio-K+ CI1285, containing L. acidophilus CL1285 and L. casei LBC80R, and as Bio-K+ 50 Billion, containing L. acidophilus CL1285, Lacticaseibacillus casei LBC80R, and Lacticaseibacillus rhamnosus CLR2 (25494,90231,90934,95369,95403,107529). Observational research has found that providing the Bio-K+ 50 Billion product as 50-100 billion colony-forming units (CFUs) daily for 5 days to patients who are on antibiotics for at least 2 days reduces the hospital-wide incidence of C. difficile by approximately 40%. The incidence rate was decreased by at least 50% in the highest risk individuals taking this combination (107529).
• Colic. Oral inactivated Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in infants with colic shows that giving a specific multi-ingredient product (Colimil Plus, Milte Italia SPA) containing inactivated L. acidophilus 1 billion colony-forming units, lemon balm 65 mg, and German chamomile 9 mg twice daily for 4 weeks reduces crying time similarly to Limosilactobacillus reuteri DSM 17938 100 million CFUs daily (96278). It is unclear how L. acidophilus compares with no treatment.
• Common cold. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in school children shows that taking a combination of L. acidophilus and Bifidobacterium bifidum (Infloran, Berna) 1 billion colony-forming units each twice daily for 3 months reduces the absolute percentage of school absence due to cold symptoms by 30% when compared with placebo (90286).
• Constipation. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that stool frequency is increased and symptoms of functional constipation in adults are improved with the use of a specific combination product (Hexbio) providing L. acidophilus, Lacticaseibacillus casei, Lactobacillus delbrueckii subsp. lactis, Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium longum subsp. infantis 30 billion colony-forming units (CFUs) twice daily for 7 days (90266). However, most other probiotic compounds containing L. acidophilus have not demonstrated benefit in most patients with constipation. One small clinical trial shows that taking yogurt 180 mL providing L. acidophilus NCFM, Bifidobacterium animalis subsp. lactis HN019, and polydextrose (Litesse) daily for 2 weeks modestly improves clinical response and reduces transit time when compared with taking a control yogurt. However, there was no effect on the number of daily bowel movements (90275). Other studies show that taking Lactobacillus acidophilus DDS-1 6.6 billion CFUs daily for 4 weeks in combination with Bifidobacterium longum UABl-14, Bifidobacterium animalis subsp. lactis UABla-12, Bifidobacterium bifidum UABb-10, and fructo-oligosaccharides (FOS) 7 mg does not improve symptoms of constipation when compared with a placebo providing FOS (110970). Also, there was a general lack of support for symptom improvement following the intake of Lactobacillus acidophilus NCFM 10 billion CFUs daily with Lacticaseibacillus paracasei Lpc-37 and Bifidobacterium animalis subsp. lactis strains Bl-04, Bi-07, and HN019 daily for 2 weeks (110979).
• Critical illness (trauma). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in critically ill, hospitalized adults shows that taking L. acidophilus LA-5 1.75 billion colony-forming units (CFUs), Lactiplantibacillus plantarum 500 million CFUs, Bifidobacterium animalis subsp. lactis BB12 1.75 billion CFUs, and Saccharomyces boulardii 1.5 billion CFUs twice daily for 15 days modestly reduces the risk of sepsis, as well as the length of stay in the ICU and hospital, when compared with placebo (107524).
• Denture stomatitis. Although there has been interest in using oral Lactobacillus acidophilus for denture stomatitis, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• Depression. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with major depression shows that taking L. acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum daily for 8 weeks reduces symptoms of depression measured on the Beck Depression Inventory (BDI) when compared with placebo (99780). However, the validity of the results from this study is limited by incomplete reporting. For example, patient baseline BDI scores were not reported.
• Diabetes. Oral Lactobacillus acidophilus in combination with other probiotic species seems to be beneficial for the treatment of gestational diabetes, although it is unclear if it is beneficial for treatment of type 1 or type 2 diabetes. Oral L. acidophilus is unlikely to be beneficial for the prevention of gestational diabetes. Details: Although some individual studies disagree, meta-analyses of clinical research in patients with gestational diabetes show that taking probiotics, most often L. acidophilus in combination with other species, improves glycemic indices such as fasting blood glucose and insulin sensitivity when compared with placebo (102288,104156). Also, one meta-analysis of clinical research shows that taking probiotics specifically containing L. acidophilus in combination with other species modestly improves these glycemic indices, as well as levels of total cholesterol and triglycerides, but not low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol (111796). Some doses used in available studies include a combination of freeze-dried L. acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum each as 2 billion colony-forming units (CFUs) per gram daily for 6 weeks (95416,98430), a total of 4 billion CFUs of a combination of L. acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, Streptococcus thermophilus STY-31, and Lactobacillus delbrueckii subsp. bulgaricus LBY-27 for 8 weeks starting at 24-28 weeks' gestation (96892), and a specific product containing L. acidophilus and 7 other probiotics (Visbiome, ExeGi Pharma) as a total of 112.5 billion CFUs twice daily for 8 weeks (107549). Meta-analyses in patients with gestational diabetes show that taking probiotics such as L. acidophilus does not reduce the risk for caesarean section birth, neonatal hypoglycemia, large for gestational age birth, or hypertensive disorders such as pregnancy-induced hypertension, pre-eclampsia, or eclampsia (102288,104156,111796). However, one meta-analysis of clinical research shows that taking probiotics specifically containing L. acidophilus modestly reduces neonatal birth weight, but not maternal weight gain (111796). Taking L. acidophilus does not seem to be effective for PREVENTING gestational diabetes. A large clinical trial shows that taking L. acidophilus LA1 7.5 billion CFUs, Bifidobacterium longum sp54 cs 1.5 billion CFUs, and Bifidobacterium bifidum sp9 cs 6 billion CFUs daily from 14-24 weeks' gestation does not reduce the incidence of gestational diabetes when compared with taking placebo (107520). Research on the use of L. acidophilus for type 2 diabetes is mixed. Taking a combination of L. acidophilus, Bifidobacterium bifidum, and Streptococcus thermophilus daily for 12 weeks does not reduce levels of fasting blood glucose or glycated hemoglobin (HbA1c) when compared with placebo (107521). One clinical study shows that taking L. acidophilus along with six other probiotic strains (Familact) daily for 6 weeks reduces fasting blood glucose, but does not affect plasma insulin, when compared with placebo (99790). A small clinical trial shows that taking fermented goat milk 120 grams containing one billion CFUs each of L. acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 daily for 6 weeks modestly reduces levels of HbA1c and low-density lipoprotein (LDL) cholesterol, but not fasting blood glucose or insulin resistance, when compared with conventional fermented milk containing Streptococcus thermophilus TA-40 (110973). However, other clinical research shows that taking L. acidophilus 1 billion CFUs, along with Lacticaseibacillus rhamnosus, Bacillus coagulans GanedenBC30 (GBI-30, 6086), and fructo-oligosaccharides 500 mg daily for 12 weeks modestly reduces fasting blood glucose and insulin and improves measures of insulin resistance when compared with placebo (107731). Another clinical trial shows that taking yogurt 200 grams daily containing L. acidophilus 4.65 million CFUs per gram along with Bifidobacterium animalis subsp. lactis modestly reduces levels of HbA1c, triglyceride, and LDL cholesterol, but not fasting glucose, when compared with a placebo yogurt (111798). A combination probiotic containing L. acidophilus has also been evaluated in children 2-12 years of age with new-onset type 1 diabetes. One clinical study shows that taking a specific combination product (Visbiome, ExeGi Pharma) providing 112.5 billion CFUs daily for 3 months modestly decreases HbA1c and insulin requirements when compared with placebo. Also, about three times as many children achieved remission, defined as insulin requirements of less than 0.5 U/kg daily and HbA1c less than 7%. However, C-peptide levels and the maintenance of residual pancreatic beta-cell function were not affected when compared with placebo (107497).
• Diabetic nephropathy. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with diabetic nephropathy not taking antidiabetes drugs shows that taking a combination of L. acidophilus, Bifidobacterium bifidum, and Streptococcus thermophilus daily for 12 weeks modestly reduces the ratio of microalbuminuria/creatinine (mAlb/Cr), a marker of kidney damage, when compared with placebo. However, there was no effect on the estimated glomerular filtration rate (eGFR) (107521).
• Diarrhea. Oral heat-killed L. acidophilus seems to reduce the duration of diarrhea in adults and children. Oral live L. acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing live L. acidophilus, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum subsp. infantis, Bifidobacterium breve, and Streptococcus thermophilus daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). Heat-killed L. acidophilus has also been investigated for the treatment of diarrhea. A meta-analysis of four small clinical studies in infants and children ages 1 month to 4 years shows that taking heat-killed L. acidophilus LB 20-30 billion colony-forming units (CFUs) daily for up to 5 days along with oral or intravenous rehydration therapy can modestly reduce the duration of diarrhea, primarily of non-rotaviral origin (90295). Also, preliminary clinical research in patients with functional chronic diarrhea shows that taking heat-killed L. acidophilus LB (Lacteol Fort, Laboratoire du Lacteol du Dr Boucard) as two capsules twice daily for a total of 20 billion cells daily for 4 weeks reduces daily stool frequency by 3.5, compared with a reduction of 1.2 in patients taking five chewable capsules three times daily of an unspecified strain of L. acidophilus (Lacidophilin, Tai Ge Pharma Ltd). Stool consistency, pain, distention, and total efficacy, defined as a decrease in mean symptoms by at least 40%, were also further improved in patients taking the heat-killed product (107537). However, other clinical research in children ages 6 months to 12 years hospitalized with acute diarrhea shows that taking 15 billion heat-killed L. acidophilus (Lactrol, Raptakos) cells daily for 3 days along with oral rehydration solution (ORS) does not have beneficial effects on duration of diarrhea, frequency of stools, or length of hospital stay, when compared with ORS alone (111789). The European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388) However, L. acidophilus is not a specific focus of the guidelines and most evidence is low quality.
• Generalized anxiety disorder (GAD). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients newly diagnosed with GAD shows that taking sertraline 25 mg plus probiotics daily for 8 weeks may modestly reduce some symptoms of anxiety when compared with sertraline alone. However, the reduction in anxiety score was small and change was not consistent between rating scales. Also, the quality of life was not improved. The probiotics provided a total of 18 billion colony-forming units of L. acidophilus, Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium animalis subsp. lactis (110977).
• Hepatic encephalopathy. Although there has been interest in using oral Lactobacillus acidophilus for hepatic encephalopathy, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• HIV/AIDS. Although there has been interest in using oral Lactobacillus acidophilus for HIV/AIDS, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• Hypercholesterolemia. It is unclear if oral Lactobacillus acidophilus is beneficial for lowering cholesterol levels; the available research is conflicting. Details: Two meta-analyses of clinical research show that taking fermented milk products containing L. acidophilus can reduce total cholesterol by about 14-19 mg/dL in adults with or without hypercholesterolemia. However, the effect of L. acidophilus on both total and LDL cholesterol levels is conflicting from available research (95396,95397,95399). Clinical trials included in these meta-analyses evaluated patients with hypercholesterolemia, type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), metabolic syndrome, and others. Taking L. acidophilus does not appear to improve high-density lipoprotein (HDL) cholesterol or triglyceride levels (95396,95397,95399). Doses used in some studies have included fermented milk products providing L. acidophilus 39 million to 2 billion CFUs daily, alone or along with other probiotic species, for up to 6 weeks (95396). One small clinical trial in patients with hypercholesterolemia shows that taking L. acidophilus LA-1 60 billion colony-forming units (CFUs) three times daily for 6 weeks does not affect serum lipids when compared with taking placebo (111791). A meta-analysis of nine small to moderate-sized clinical studies shows that taking a combination of L. acidophilus and Bifidobacterium animalis subsp. lactis reduces levels of total cholesterol when compared with placebo (107591). However, it is unclear if this is due to L. acidophilus, Bifidobacterium animalis subsp. lactis, or their combination.
• Hypertension. Although there has been interest in using oral Lactobacillus acidophilus for hypertension, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• Inflammatory bowel disease (IBD). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial in patients with collagenous colitis shows that taking 10 billion colony-forming units each of L. acidophilus LA-5 and Bifidobacterium longum subsp. lactis BB-12 twice daily for 12 weeks does not increase the proportion of patients with a reduction in weekly bowel frequency of at least 50% when compared with placebo. Also, there was no effect of this combination on stool consistency or abdominal symptoms. However, there were some modest benefits when compared with baseline (110999). This study was small and may have been underpowered to detect differences.
• Intraventricular hemorrhage. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in premature infants shows that taking 6 billion CFUs of a combination of L. acidophilus NCDO 1748 and Bifidobacterium bifidum NCDO 2203 (UFC Inforan, Switzerland) from 7 days of age until 34 weeks postmenstrual age or discharge does not reduce the odds of intraventricular hemorrhage when compared with a control group of infants not given these probiotics. The infants in this study were born at less than 32 weeks gestation and had a birthweight of less than 1500 grams (111794). This study is limited by the lack of randomization to treatment group; placement was based on year of birth.
• Lactose intolerance. It is unclear if oral Lactobacillus acidophilus is beneficial for lactose intolerance. Details: One small clinical trial shows that consuming 400 mL of a non-fermented milk product containing L. acidophilus 530 million colony-forming units (CFUs)/mL daily does not reduce symptoms of lactose intolerance or hydrogen breath test results when compared with milk without L. acidophilus (16737). Another small preliminary clinical trial shows that taking L. acidophilus BG2FO4 10 billion CFUs twice daily for 7 days does not reduce lactose-induced gastrointestinal symptoms or improve lactose digestion based on breath hydrogen when compared with baseline (111783). However, another clinical trial shows that adding various L. acidophilus strains 800 million to 1 billion CFUs/mL to non-fermented milk improves hydrogen breath tests in patients with lactose intolerance (16738).
• Lyme disease. Although there has been interest in using oral Lactobacillus acidophilus for Lyme disease, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• Metabolic syndrome. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in elderly patients with metabolic syndrome shows that taking a combination of L. acidophilus PBS066-DSM 24,936, Lactiplantibacillus plantarum PBS067-DSM 24,937, and Limosilactobacillus reuteri PBS072-DSM 25,175 as 2 billion colony-forming units (CFUs) each, with inulin and fructo-oligosaccharides daily for 60 days, reduces the number of patients diagnosed with metabolic syndrome by 23%, compared with a 10% reduction in those taking placebo. In the probiotic group, there were modest improvements in waist circumference and levels of fasting plasma insulin, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and inflammatory mediators when compared with placebo. However, there were no significant differences between groups for fasting blood glucose or blood pressure. All patients in this study were on a Mediterranean-like standard diet (107560).
• Necrotizing enterocolitis (NEC). It is unclear if oral Lactobacillus acidophilus is beneficial or safe for NEC prevention. Details: Most meta-analyses of clinical research show that giving lactobacilli enterally reduces the risk of NEC and/or severe NEC in preterm, mainly very low birth weight (VLBW), infants. Some meta-analyses support the use of lactobacilli in combination with bifidobacteria, as opposed to lactobacilli alone for reducing the risk of NEC. However, only a small number of the individual studies included in these analyses have investigated the effects of L. acidophilus, which was used as part of a combination probiotic and/or prebiotic product in all cases (95344,95351,103437,103445,104157,105162,105164). Also, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, L. acidophilus is not specifically recommended (103003,111609,111611).
• Nonalcoholic fatty liver disease (NAFLD). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children with NAFLD, clinical research shows that taking a specific combination product (Prokid, Gostaresh Milad Pouya Company) containing L. acidophilus ATCC B3208 3 billion colony-forming units (CFUs), Lacticaseibacillus rhamnosus DSMZ 21690 2 billion CFUs, Bifidobacterium animalis subsp. lactis DSMZ 32269 6 billion CFUs, and Bifidobacterium bifidum ATCC SD6576 2 billion CFUs daily for 12 weeks normalizes liver sonography findings in 53% of children, compared with 17% of those taking placebo. In addition, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are reduced by 30% and 25%, respectively. There was no effect on body mass index or blood lipids when compared with placebo (105156). Another clinical trial shows that taking two sachets daily for 3 months of a specific combination product (VSL#3) containing L. acidophilus and other probiotics modestly decreases triglyceride levels and liver enzymes when compared with taking placebo. However, there was no change in body mass index or most glycemic or lipid parameters (111009). However, taking L. acidophilus in combination with other probiotics does not seem to be beneficial in adults with NAFLD. Clinical research shows that taking yogurt 100 grams, containing L. acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12 40 million CFUs and vitamin D 1000 IU, daily for 3 months does not improve fasting blood glucose levels, insulin levels, blood pressure, or anthropometric indices when compared with unfortified yogurt (105174). Also, a small clinical trial shows that taking a combination of L. acidophilus BCMC 12,130, Lacticaseibacillus casei BCMC 12,313, Lactobacillus delbrueckii subsp. lactis BCMC 12,451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum subsp. infantis BCMC 02129, and Bifidobacterium longum BCMC 02120 30 billion colony-forming units twice daily for 6 months has no beneficial effects on hepatic steatosis or fibrosis or on levels of liver enzymes, blood lipids, or fasting glucose, when compared with placebo (107523).
• Nonalcoholic steatohepatitis (NASH). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with NASH shows that taking 1 billion colony-forming units each of L. acidophilus ATCC SD5221 and Bifidobacterium animalis subsp. lactis HN019 daily for 6 months does not have beneficial effects on severity of liver fibrosis or steatosis, metabolic markers, or inflammation when compared with taking placebo. The effect of this combination on liver enzymes was mixed (111797).
• Obesity. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In combination with Bifidobacterium animalis subsp. lactis BS01, taking L. acidophilus LA02 2 billion colony-forming units (CFUs) daily for 6 weeks does not reduce body weight or body fat when compared with placebo in young, healthy females, only some of whom were overweight (103438). However, another clinical study shows that taking 50 billion CFUs of a specific combination of L. acidophilus, Lactiplantibacillus plantarum, Bifidobacterium bifidum, and B. animalis subsp. lactis (Lab4P) for 24 weeks reduces body weight by an additional 1.3 kg more than placebo (103439).
• Polycystic ovary syndrome (PCOS). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with PCOS, clinical research shows that taking a combination of L. acidophilus T16 (IBRC-M10785), Lacticaseibacillus casei T2 (IBRC-M10783), and Bifidobacterium bifidum T1 (IBRC-M10771) 2 billion colony-forming units each, plus inulin 800 mg, daily for 12 weeks modestly reduces serum insulin and triglyceride levels and improves insulin resistance and insulin sensitivity when compared with placebo. However, it does not alter cholesterol or fasting glucose levels (105159). Another clinical trial shows that 31.3% of patients with PCOS taking L. acidophilus in combination with other probiotics daily for 6 months had regular menstrual cycles compared with 12.5% of those taking placebo. There were also modest improvements in testosterone levels and waist circumference, but not other hormones, insulin resistance, body weight, or most measures of quality of life. The product provided Lactobacillus acidophilus UBLA-34 2 billion CFUs along with Bifidobacterium bifidum UBBB-55, Lactiplantibacillus plantarum UBLP-40, Lacticaseibacillus casei UBLC-42, Limosilactobacillus fermentum UBLF-31, Lacticaseibacillus rhamnosus UBLR-58, Limosilactobacillus reuteri UBLRu-87, and fructo-oligosaccharides (FOS) daily for 2 months and then twice daily for 4 months. All patients also underwent dietary and lifestyle changes (110974).
• Postoperative infection. Although there has been interest in using oral Lactobacillus acidophilus for preventing postoperative infections, there is insufficient reliable information about the clinical effects of lactobacillus for this purpose.
• Pouchitis. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Continuous oral treatment for one year with a specific concentrated formulation of L. acidophilus and other probiotics (Visbiome, ExeGi Pharma) as 6 grams (300-500 billion live bacteria per gram), daily for up 12 months seems to maintain remission of pouchitis in 85% of patients (6087,12769). Also, one small clinical study shows that taking a specific product (Trilac, Allergon AB) containing L. acidophilus 600 million colony-forming units (CFUs) per capsule, Lactobacillus delbrueckii subsp. bulgaricus 400 million CFUs per capsule, and Bifidobacterium bifidum 600 million CFUs per capsule, taken in doses of two capsules three times daily for 9 months, can reduce pouchitis severity and the number of patients experiencing pouchitis when compared to baseline (90296). The validity of these findings is limited by the lack of a comparator group.
• Pregnancy-induced nausea and vomiting. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units (CFUs) of L. acidophilus La-14, Lactiplantibacillus plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Lacticaseibacillus paracasei DSM 13434 and Lpc-37, Ligilactobacillus salivarius Ls-33, Levilactobacillus brevis Lbr-35, Lacticaseibacillus casei Lc-11, and Bifidobacterium animalis subsp. lactis Bl-04, along with inulin 200 mg (107199).
• Prematurity. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In premature infants, clinical research shows that taking a blend of L. acidophilus, bifidobacteria, and Enterococcus faecalis (Peifeikang powder, Shanghai Xinyi Pharmaceutical Company), at least 5 million colony-forming units (CFUs) three times daily from birth until implementation of total parenteral nutrition, reduces the rate of development of extrauterine growth retardation from 15% to 8% when compared with those not receiving this blend (103448). Other preliminary clinical research in premature infants shows that taking 6 billion CFUs of a combination of L. acidophilus NCDO 1748 and Bifidobacterium bifidum NCDO 2203 (UFC Inforan, Switzerland) from 7 days of age until 34 weeks postmenstrual age or discharge reduces the odds of neurodevelopment impairment at 24 months corrected age by 70% when compared with a control group of infants not given these probiotics. The odds of having moderate to severe impairment were also reduced. The infants in this study were born at less than 32 weeks gestation and had a birthweight of less than 1500 grams (111794). This study is limited by the lack of randomization to treatment group; placement was based on year of birth. Observational research has also been conducted. One large observational study in infants fed strictly human milk, but not strictly formula or a combination, suggests that taking L. acidophilus 1 to 3 billion CFUs with Bifidobacterium longum subsp. infantis during the first month of life for the prevention of necrotizing enterocolitis was associated with a modest increased weight gain velocity. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Psoriasis. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with psoriasis shows that taking a mixture of probiotics for 8 weeks modestly improves overall symptoms and feelings of depression when compared with placebo. The percentage of patients achieving at least a 50% or 75% reduction in overall symptom score was 40% and 24%, respectively, in those taking the probiotic mixture, compared with 16% and 8% of those taking placebo. Each probiotic capsule was used twice daily and provided a total daily dose of 2.6 billion colony-forming units (CFUs) of L. acidophilus, Bifidobacterium bifidum, Bifidobacterium animalis subsp. lactis, and Bifidobacterium longum (107498).
• Radiation-induced diarrhea. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with cervical cancer receiving radiotherapy with or without chemotherapy shows that taking a specific product (Biogurt, Fame Pharmaceuticals) containing L. acidophilus LA-5 and Bifidobacterium animalis subsp. lactis BB-12 as 1.75 billion lyophilized colony-forming units (CFUs) as a capsule three times daily throughout treatment reduces the risk of diarrhea by 28% when compared with placebo. The treatment group also used less loperamide (102285). Another small clinical trial in patients undergoing pelvic radiotherapy with weekly cisplatin shows that taking L. acidophilus and Bifidobacterium bifidum (Infloran, Laboratio Farmaceutico SIT) as 1 billion CFUs each, twice daily from seven days before starting radiotherapy and continuing during radiotherapy, reduces the incidence of moderate to severe diarrhea and the need for antidiarrheal medication when compared with placebo. Moderate to severe diarrhea occurred in 9% of patients using the probiotics, compared with 45% of those taking placebo (107580).
• Respiratory tract infections. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children ages 3-5 years who attend daycare centers shows that taking a combination milk product containing 5 billion colony-forming units (CFUs) each of L. acidophilus and Bifidobacterium animalis (HOWARU Protect, Danisco) reduces the risk of experiencing fever, cough, and rhinorrhea by 45% when compared with placebo. Patients taking this combination experienced an average 2-day shorter duration of symptoms and were significantly less likely to use an antibiotic for their symptoms. Patients who took L. acidophilus without bifidobacterium also had a reduction in fever, cough, and use of antibiotics, but not rhinorrhea (16847). In healthy children aged 3-10 years, clinical research shows that taking 12.5 billion CFUs daily of a specific combination of L. acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20, Bifidobacterium animalis subsp. lactis CUL34 (Lab4), and vitamin C 50 mg daily reduces the risk of cough by 16% and sore throat by 20%, and modestly reduces school absenteeism and antibiotic use when compared with placebo. However, nasal symptoms, fever, and wheezing were not reduced (106943). A different combination product containing L. acidophilus DDS-1 1 billion CFUs and B. animalis subsp. lactis UABLA-12 4 billion CFUs (Up4-Junior, UAS Laboratories) with fructo-oligosaccharides 50 mg has also been evaluated. Clinical research in children 3-12 years of age with a sick household member shows that taking this product daily for 2 weeks modestly shortens the duration of respiratory infections, but does not reduce the risk of developing an infection, when compared with placebo (98439). In overweight adults or adults with obesity, taking 50 billion CFUs of a specific combination of L. acidophilus, Lactiplantibacillus plantarum, B. bifidum, and B. animalis subsp. lactis (Lab4P) for 24 weeks reduces the overall likelihood of having upper respiratory tract infection symptoms, such as sneezing, cough, and blocked nose, by approximately 40% when compared with placebo (103439).
• Retinopathy of prematurity. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in premature infants shows that taking 6 billion CFUs of a combination of L. acidophilus NCDO 1748 and Bifidobacterium bifidum NCDO 2203 (UFC Inforan, Switzerland) from 7 days of age until 34 weeks postmenstrual age or discharge does not reduce the odds of retinopathy of prematurity when compared with a control group of infants not given these probiotics. The infants in this study were born at less than 32 weeks gestation and had a birthweight of less than 1500 grams (111794). This study is limited by the lack of randomization to treatment group; placement was based on year of birth. Also, one large observational study in premature infants suggests that taking L. acidophilus 1 to 3 billion CFUs with Bifidobacterium longum subsp. infantis during the first month of life for the prevention of necrotizing enterocolitis was not associated with a reduced risk of retinopathy of prematurity. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Rheumatoid arthritis (RA). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with moderate-to-severe RA shows that taking capsules containing freeze-dried strains of L. acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum daily for 8 weeks does not improve RA severity, the number of tender or swollen joints, or joint pain when compared with placebo (95418).
• Rotaviral diarrhea. It is unclear if oral Lactobacillus acidophilus is beneficial for rotaviral diarrhea. Details: One preliminary clinical study shows that taking a combination of L. acidophilus AD031 2 billion colony-forming units (CFUs) and Bifidobacterium longum BORI 20 billion CFUs twice daily for 3 days reduces the duration of rotaviral diarrhea by an average of 3 days when compared with placebo (95334). However, one clinical study using a lower dose and different strain of L. acidophilus (La-14) 200 million CFUs twice daily for 5 days shows that this regimen does not reduce the duration of watery diarrhea or affect the viral load in children aged 9 months to 5 years with confirmed norovirus or rotavirus infection (96887). A small clinical study shows that heat-killed L. acidophilus LB 20-30 billion cells daily for up to 4 days can modestly reduce the duration of diarrhea in infants and children, some of which had confirmed rotavirus (90295).
• Sepsis. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in premature infants shows that taking 6 billion CFUs of a combination of L. acidophilus NCDO 1748 with Bifidobacterium bifidum NCDO 2203 (UFC Inforan, Switzerland) from 7 days of age until 34 weeks postmenstrual age or discharge reduces the odds of late onset sepsis by 55% when compared with a control group of infants not given these probiotics. The infants in this study were born at less than 32 weeks gestation and had a birthweight of less than 1500 grams (111794). This study is limited by the lack of randomization to treatment group; placement was based on year of birth. One large observational study in infants fed a mix of human milk and formula, but not strictly human milk or formula, suggests that taking L. acidophilus 1 to 3 billion CFUs with Bifidobacterium longum subsp. infantis during the first month of life for the prevention of necrotizing enterocolitis was associated with a 31% reduction in the development of clinical sepsis. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Short bowel syndrome. Although there has been interest in using oral Lactobacillus acidophilus for short bowel syndrome, there is insufficient reliable information about the clinical effects of lactobacillus for this condition.
• Small intestinal bacterial overgrowth (SIBO). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with chronic diarrhea due to SIBO shows that taking a combination of lyophilized L. acidophilus 1.5 grams and Lacticaseibacillus casei 1.5 grams by mouth twice daily for 21 days decreases average daily stools by 1.5, but does not improve other symptoms, when compared with placebo (91143). Also, one preliminary clinical study shows that taking a total of 2 billion CFUs of L. acidophilus and Lacticaseibacillus rhamnosus (Lacidofil) daily for 4 weeks does not prevent the development of SIBO in children that started treatment with omeprazole 20 mg daily for epigastric pain (90262).
• Travelers' diarrhea. It is unclear if oral Lactobacillus acidophilus is beneficial for the prevention of travelers' diarrhea. Details: A meta-analysis which included three clinical studies evaluating the use of L. acidophilus in adults traveling to different parts of the world found no benefit for the prevention of travelers' diarrhea when compared with placebo (101445). The effectiveness of this species may vary significantly based upon the destination of travel. Destinations in the same country can have different results, probably due to differences in bacteria and other microorganisms at different locations (10216).
• Ulcerative colitis. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: The best evidence of benefit is for a specific combination product (Visbiome, ExeGi Pharma). Doses of 3 grams (equivalent to 900 billion colony-forming units (CFUs)) once or twice daily have been used in combination with conventional treatment. In children aged 1-16 years, doses of 450-1800 billion CFUs for up to one year have been used (3261,14370,14371,16841,95337). A meta-analysis of clinical research shows that taking this product as an adjunct to standard ulcerative colitis treatment can increase remission rates in adults and children by about 1.7-fold when compared with standard treatment alone (95337). Preliminary clinical research in patients with moderate to severe symptoms taking mesalazine 1200 mg daily shows that taking an unknown dose of L. acidophilus twice daily along with Bifidobacterium bifidum BGN4 and Ligilactobacillus salivarius (Acronelle, Bromatech srl, Milan, Italy) for 2 years modestly improves patient- and physician-scales of overall symptoms when compared with taking mesalazine alone. There were also improvements in stool frequency and rectal bleeding (110981). Although some contradictory evidence exists (3261,16841), most research shows that taking Visbiome or a combination of L. acidophilus LA-5 and Bifidobacterium animalis subsp. lactis BB-12 (Probio-Tec AB-25) does not prevent relapse in people who are already in remission (95337,95338).
• Urinary tract infections (UTIs). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children aged 4 months to 5 years with a previous UTI, clinical research shows that taking a specific combination of L. acidophilus, Lacticaseibacillus rhamnosus, Bifidobacterium bifidum, and Bifidobacterium animalis subsp. lactis (Complete Probiotic Platinum) for 18 months increases the median time to the first incidence of recurrence by approximately 3 months and increases the percentage of children without a UTI during the study period from 83% to 97% (103436).
• Vaginal candidiasis. It is unclear if oral or intravaginal Lactobacillus acidophilus is beneficial for vaginal candidiasis. Details: In a small preliminary clinical trial in patients with recurrent vulvovaginal candidiasis who had undergone a week of oral fluconazole treatment followed by intravaginal L. acidophilus LA 02 and Limosilactobacillus fermentum LF10, 72.4% of patients demonstrated a lack of clinical recurrence over a 7 month observational period. All patients took fluconazole 200 mg three times in the first week followed by intravaginal application with at least 0.4 billion colony-forming units each of L. acidophilus LA 02 and Limosilactobacillus fermentum LF10, along with arabinogalactan and fructo-oligosaccharides (FOS) on alternate days for 10 days and then once weekly for 10 weeks (111781). However, a combination of L. acidophilus, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii, and Streptococcus thermophilus (Femilac) given intravaginally, does not seem to reduce the risk of vaginal candidiasis infection following use of antibiotics (12108). There is also some evidence that eating yogurt enriched with L. acidophilus daily does not reduce the risk of recurrent vaginal candidiasis (1245).
• Ventilator-associated pneumonia (VAP). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking L. acidophilus LA-5 1.75 billion colony-forming units (CFUs), Lactiplantibacillus plantarum 500 million CFUs, Bifidobacterium animalis subsp. lactis BB12 1.75 billion CFUs, and Saccharomyces boulardii 1.5 billion CFUs twice daily for 15 days reduces the risk of VAP to 12%, compared with 28% in those taking placebo. Half of the dose was given onto the oropharynx and half via a nasogastric tube (107524). More evidence is needed to rate Lactobacillus acidophilus for these uses.

(Read more about LACTOBACILLUS ACIDOPHILUS)

LIKELY SAFE ...when aloe gel is used topically and appropriately. Aloe gel-containing formulations have been safely applied in clinical trials (101,11982,12096,12098,12159,12160,12163,12164,17418)(90123,90124,90127,90128,90129,90131,97320,98816,103305). When included in topical cosmetics, the Cosmetic Ingredient Review Expert Panel concluded that aloe-derived anthraquinone levels should not exceed 50 ppm (90122).

POSSIBLY SAFE ...when aloe gel is used orally and appropriately, short-term. Aloe gel has been safely used in a dose of 15 mL daily for up to 42 days or 100 mL of a 50% solution twice daily for up to 4 weeks (11984,12164). Also, a specific aloe gel complex (Aloe QDM complex, Univera Inc.) has been safely used at a dose of approximately 600 mg daily for up to 8 weeks (90121). ...when aloe extract is used orally and appropriately, short-term. Aloe extract has been used with apparent safety in a dose of 500 mg daily for one month (101579). Also, an aloe extract enriched in aloe sterols has been used with apparent safety in a dose of 500 mg daily for 12 weeks (101577).

POSSIBLY UNSAFE ...when aloe latex is used orally. There is some evidence that anthraquinones in aloe latex are carcinogenic or promote tumor growth, although data are conflicting (6138,16387,16388,91596,91597). In 2002, the US FDA banned the use of aloe latex in laxative products due to the lack of safety data (8229). ...when aloe whole-leaf extract is used orally. Aloe whole-leaf extract that has not been filtered over charcoal still contains anthraquinones. This type of aloe whole-leaf extract is referred to as being "nondecolorized". The International Agency for Research on Cancer has classified this type of aloe whole-leaf extract as a possible human carcinogen (91598,91908). Although filtering aloe whole-leaf extract over charcoal removes the anthraquinones, some animal research suggests that this filtered extract, which is referred to as being "decolorized", may still cause gene mutations (91598). This suggests that constituents besides anthraquinones may be responsible for the carcinogenicity of aloe whole-leaf extract. It should be noted that commercial products that contain aloe whole-leaf extract may be labeled as containing "whole leaf Aloe vera juice" or "aloe juice" (91908).

LIKELY UNSAFE ...when aloe latex is used orally in high doses. Ingesting aloe latex 1 gram daily for several days can cause nephritis, acute kidney failure, and death (8,8961).

CHILDREN: POSSIBLY SAFE
when aloe gel is used topically and appropriately. Aloe gel-containing formulations have been safely applied in clinical trials (90124,90131).

CHILDREN: POSSIBLY UNSAFE
when aloe latex and aloe whole leaf extracts are used orally in children. Children younger than 12 years may experience abdominal pain, cramps, and diarrhea (4).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Anthraquinones present in aloe latex and aloe whole leaf extracts have irritant, cathartic, and possible mutagenic effects (4,16387,16388,90122). There are also anecdotal reports and evidence from animal research that anthraquinones or aloe whole leaf extracts might induce abortion and stimulate menstruation; avoid using (4,8,19,90122).

LACTATION: POSSIBLY UNSAFE
when aloe preparations are used orally. Cathartic and mutagenic anthraquinones present in aloe latex and aloe whole leaf extracts might pass into milk; avoid using (4,19).

(Read more about ALOE)

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

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12). There is insufficient reliable information available about the safety of dandelion when used topically.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those in foods.

(Read more about DANDELION)

POSSIBLY SAFE ...when used topically and appropriately. Gotu kola has been used safely in a cream or ointment for up to 10 weeks (11072,11073,67372,102792,105329,105335). An emulsion containing gotu kola extract 3% and other ingredients has been applied safely to the skin twice daily for up to 60 days (111571). ...when used orally and appropriately. Gotu kola extract has been used with apparent safety in doses of up to 180 mg daily for up to 12 months or 1000 mg daily for 60 days. Dried gotu kola has been used with apparent safety in doses of up to 2200 mg daily for 4 weeks (6887,11062,11063,11064,11065,11066,11067,11068,11069,11070)(11071,99756,99757,99758,105329,105332,105333). A specific gotu kola extract (Centellicum, Horphag Research Ltd) 450-675 mg daily has been used with apparent safety for up to 6 weeks (99756,99757).

PREGNANCY: POSSIBLY SAFE
when used topically and appropriately (11073,13559). There is insufficient reliable information available about the safety gotu kola when used orally during pregnancy; avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally and appropriately. Lactobacillus acidophilus has been safely used as part of multi-ingredient probiotic products in studies lasting up to nine months (1731,6087,14370,14371,90231,90296,92255,103438,12775,107581)(110950,110970,110979,110998,111785,111793). ...when used intravaginally and appropriately. L. acidophilus has been used safely in studies lasting up to 12 weeks (12108,13176,13177,90265). There is insufficient reliable information available about the safety of non-viable, heat-killed L. acidophilus formulations when used orally.

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Lactobacillus acidophilus has been safely used for up to 5 days (96887). Also, combination probiotics containing L. acidophilus have been used with apparent safety in various doses and durations. L. acidophilus has been combined with Bifidobacterium animalis (HOWARU Protect, Danisco) for up to 6 months in children 3-5 years old (16847), with Bifidobacterium bifidum for 6 weeks (90602,96890), with Bifidobacterium bifidum and Bifidobacterium animalis subsp. lactis (Complete Probiotic Platinum) for 18 months in children 4 months to 5 years of age (103436), and in a specific product (Visbiome, ExeGi Pharma) containing a total of 8 species for 3 months in children 2-12 years old (107497). There is insufficient reliable information available about the safety of L. acidophilus in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. A combination of Lactobacillus acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum has been used with apparent safety for 6 weeks, starting at 24-28 weeks' gestation (95416,98430).

LACTATION:
There is insufficient reliable information available about the safety of Lactobacillus acidophilus during lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe gel might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro research shows that aloe gel can inhibit platelet aggregation. This inhibition was greater than that seen with celecoxib, but less than that seen with aspirin (105501).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Aloe might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Preliminary clinical research suggests aloe gel might lower blood glucose levels (11983,12164,19756) and have additive effects when used with antidiabetes drugs. Monitor blood glucose levels closely.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe might decrease the levels and clinical effects of CYP1A2 substrates.  Details In vitro research shows that aloe extract induces CYP1A2 enzymes (111404).

DIGOXIN (Lanoxin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, aloe latex might increase the risk of adverse effects when taken with cardiac glycosides.  Details Overuse of aloe latex can increase the risk of adverse effects from cardiac glycoside drugs, such as digoxin, due to potassium depletion. Overuse of aloe, along with cardiac glycoside drugs, can increase the risk of toxicity (19).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe latex might increase the risk of hypokalemia when taken with diuretic drugs.  Details Overuse of aloe latex might compound diuretic-induced potassium loss, increasing the risk of hypokalemia (19).

STIMULANT LAXATIVES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe latex might increase the risk for fluid and electrolyte loss when taken with stimulant laxatives.  Details Due to cathartic laxative effects of aloe latex, concomitant use with other stimulant laxatives might compound fluid and electrolyte loss (19,19742,19743,19744).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe latex might increase the risk of bleeding when taken with warfarin.  Details Aloe latex has stimulant laxative effects. In some people aloe latex can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. Advise patients who take warfarin not to take excessive amounts of aloe vera.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking dandelion root along with anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.  Details In vitro research suggests that dandelion root inhibits platelet aggregation (18291).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the risk for hypoglycemia when used with antidiabetes drugs.  Details Laboratory research suggests that dandelion extract may have moderate alpha-glucosidase inhibitor activity and might also increase insulin secretion (13474,90926). Also, in a case report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemia 2 weeks after beginning to eat salads containing dandelion (46960).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase levels of drugs metabolized by CYP1A2.  Details Laboratory research suggests that dandelion might inhibit CYP1A2 (12734). So far, this interaction has not been reported in humans. However, until more is known, watch for an increase in the levels of drugs metabolized by CYP1A2 in patients taking dandelion.

GLUCURONIDATED DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the clearance of drugs that are UDP-glucuronosyltransferase substrates.  Details There is some preliminary evidence that dandelion might induce UDP-glucuronosyltransferase, a phase II enzyme (12734).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, through diuretic effects, dandelion might reduce excretion and increase levels of lithium.  Details Animal research suggests that dandelion has diuretic properties (13475). As diuretics can increase serum lithium levels, the dose of lithium might need to be decreased when taken with dandelion.

POTASSIUM-SPARING DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.  Details Dandelion contains significant amounts of potassium (13465).

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might lower fluoroquinolone levels.  Details Animal research shows that dandelion reduces absorption of ciprofloxacin and can lower levels by 73% (13477). However, this effect has not been reported in humans.

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CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking gotu kola might increase the sedative effects of CNS depressants.  Details In vitro research suggests that gotu kola may have sedative effects via binding of GABA receptors (6887,11071).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking gotu kola with hepatotoxic drugs might have additive adverse effects.  Details There are at least four case reports of hepatotoxicity associated with the use of gotu kola. However, more information is needed to determine if gotu kola was the causative factor in these cases (13182,92506).

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ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lactobacillus acidophilus with antibiotic drugs might decrease the effectiveness of L. acidophilus.  Details L. acidophilus preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. acidophilus preparations by at least two hours.

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General ...Orally and topically, aloe products are generally well tolerated when used in typical doses. However, oral aloe latex is associated with a greater risk of adverse effects, especially when used in high doses or long-term.
Most Common Adverse Effects:
Orally: Aloe latex may cause abdominal pain, cramps, and diarrhea.
Topically: Burning, erythema, and itching. Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Aloe latex is associated with serious adverse effects when taken in high doses or long-term. Cases of acute hepatitis due to a hypersensitivity reaction to aloe leaf extract has been reported.

Dermatologic ...Topically, aloe gel has occasionally been associated with burning (12164,19741,30697,30706), itching (12164,19741,30697), eczema (90122), erythema (19748,30706,90123), contact dermatitis (12163,12164,30695,30736,30737,30738,30740), popular eruption (30732), and urticaria (30712). Also, a case of generalized nummular and popular dermatitis attributed to hypersensitivity has been reported for a 47-year-old male who used aloe leaf gel, both topically and orally, for 4 years (30740).

Endocrine ...A case of severe hypokalemia has been reported for a male breast cancer patient who was undergoing chemotherapy and using aloe vera 1 liter daily orally for 2 weeks. The hypokalemia was attributed to the cathartic effects of aloe and resolved once aloe use was discontinued (30704).

Gastrointestinal ...Orally, aloe latex can cause abdominal pain and cramps. Long-term use or abuse of aloe latex can cause diarrhea, sometimes with hypokalemia, albuminuria, hematuria, muscle weakness, weight loss, arrhythmia, and pseudomelanosis coli (pigment spots in intestinal mucosa). Pseudomelanosis coli is believed to be harmless, and usually reverses with discontinuation of aloe. It is not directly associated with an increased risk of developing colorectal adenoma or carcinoma (6138). Orally, aloe gel may cause nausea, stomach cramps, and other gastrointestinal complaints in some patients (104174,111921,111663).
Topically, applying aloe gel in the mouth may cause nausea within 5 minutes of application in some patients (90124).

Hematologic ...A case of Henoch-Schonlein purpura, characterized by abdominal pain, purpura, and severe arthralgia, has been reported in a 52-year-old male who drank aloe juice prepared from four to five leaflets for 10 days prior to symptom development (91598).

Hepatic ...Cases of acute hepatitis have been reported after ingestion of aloe leaf extracts for between 3 weeks and 5 years. This is thought to be a hypersensitivity reaction (15567,15569,16386,17419,90126,91598). A case of acute hepatitis has also been reported for a 45-year-old female who drank two ounces of Euforia juice (Nuverus International), a product containing green tea, noni, goji, and aloe, daily for one month (90125). However, one small clinical trial in healthy individuals shows that taking aloe gel 2 ounces twice daily for 60 days does not impair liver function (104174).

Renal ...Orally, aloe latex can cause hemorrhagic gastritis, nephritis, and acute kidney failure following prolonged use of high doses (1 gram daily or more) (8961).

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General ...Orally, dandelion seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, heartburn, and stomach discomfort.
Topically: Dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.

Cardiovascular ...In one report, a 39-year-old obese woman developed palpitations and syncope after taking a weight loss supplement containing a combination of dandelion, bladderwrack, and boldo for 3 weeks. The patient was found to have prolonged QT-interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether dandelion, another ingredient, or the combination of ingredients is responsible for this adverse effect. The product was not analyzed to determine the presence of any potential toxic contaminants.

Dermatologic ...Topically, dandelion can cause contact dermatitis and erythema multiforme in sensitive individuals. Dandelion can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family (13478,13481,42893,46945,46977). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Endocrine ...In one report, a 56-year-old man with renal impairment developed hyperoxalaemia and peripheral gangrene after ingesting large amounts of dandelion tea (10 to 15 cups daily for 6 months). The adverse effect was attributed to the high oxalate content of dandelion tea (258 mcmol/L) and reduced renal oxalate clearance caused by renal impairment (90639). In another report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemic symptoms 2 weeks after beginning to eat salads containing dandelion (46960). The hypoglycemic effect was attributed to the potential alpha-glucosidase inhibitory activity of dandelion.

Gastrointestinal ...Gastrointestinal symptoms, including stomach discomfort, diarrhea, and heartburn, have been reported following oral use of dandelion (19146,36931). A case of intestinal blockage has been reported for a patient who ingested a large amount of dandelion greens three weeks after undergoing a stomach operation (46981). Also, a case of hemorrhagic cystitis has been reported for a 33-year-old woman who took a specific herbal product (Slim-Kombu, Balestra and Mech, Vicenza, Italy) containing 20 herbal extracts, including dandelion extract. Symptoms resolved after the patient discontinued using the product, and symptoms resumed when the patient began taking the supplement again four months later. While various ingredients in the supplement may have contributed to the symptoms, it is possible that dandelion extract may have contributed to the effect due to its diuretic, laxative, cholagogue, and antirheumatic properties (46959).

Other ...Orally, products containing dandelion pollen can cause allergic reactions, including anaphylaxis (13479,13480). Also, rhinoconjunctivitis and asthma have been reported after handling products such as bird feed containing dandelion and other herbs, with reported positive skin tests for dandelion hypersensitivity (46948). Dandelion pollen may cause pollinosis, such as allergic rhinitis and conjunctivitis (18065,46951,46964,46966,46972).

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General ...Orally and topically, gotu kola seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastric irritation and nausea.
Topically: Eczema.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity.

Dermatologic ...Topically, gotu kola may cause eczema (10277,10278). Also, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (4,6887,9789,52875,52887,52896,52902). One specific gotu kola product (Blasteostimulina,Almirall, S. A.) has been reported to cause allergic contact dermatitis. However, not all patients with reactions to this product are sensitive to gotu kola; some patients are sensitive to neomycin, another ingredient in the product (52875). Madecassol ointment (Rona Laboratories Limited) is another gotu kola product that has resulted in allergic contact dermatitis. Controlled testing suggests that this product can cause this adverse effect in about 8% of patients (9789). Centellase cream has also caused allergic contact dermatitis in at least two cases (52887,52888).

Gastrointestinal ...In some patients, gotu kola can extract cause gastrointestinal upset and nausea (780,6887,52894).

Hepatic ...There is concern that gotu kola may cause liver toxicity in some patients. There are at least four case reports of hepatotoxicity associated with gotu kola; however, hepatotoxic contaminants cannot be ruled out, as laboratory analysis was not conducted on the products used. Additionally, the doses of gotu kola used in these cases were not reported (13182,92506). In a clinical trial where liver function was monitored, taking gotu kola 120 mg daily for 6 months was not associated with changes in liver function (11065).
In one case of hepatotoxicity, a 61-year-old female developed elevated liver transaminase and total bilirubin levels after taking gotu kola tablets for 30 days. Liver biopsy showed granulomatous acute hepatitis. Months later, the patient took gotu kola again and developed elevated liver transaminases after 2 weeks. In another case, a 52-year-old female developed symptoms of hepatitis and increased liver transaminases after taking gotu kola for 3 weeks. Biopsy indicated chronic hepatitis and granulomas, areas of necrosis, and cirrhotic transformation. Liver function normalized after discontinuation of gotu kola. In a third case, a 49-year-old female developed symptoms of hepatitis after taking gotu kola for 2 months. Biopsy revealed granulomatous hepatitis. Liver function normalized after discontinuation of gotu kola (13182). In a fourth case, a 15-year-old female taking an unknown dose of gotu kola and lymecycline for 6 weeks for acne experienced acute liver failure with abdominal pain and vomiting, as well as elevated liver transaminases, bilirubin, international normalized ratio (INR), and prothrombin. Liver function returned to normal after both products were discontinued (92506).

Immunologic ...Topically, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (4,6887,9789,52875,52887,52896,52902). One specific gotu kola product (Blasteostimulina, Almirall, S. A.) has been reported to cause allergic contact dermatitis in some patients. However, not all patients who react to this product are sensitive to gotu kola; some are sensitive to neomycin, another ingredient in the product (52875). Madecassol ointment (Rona Laboratories Limited) is another gotu kola product that has resulted in allergic contact dermatitis. Controlled testing suggests that this product can cause this adverse effect in about 8% of patients (9789). Centellase cream has also caused allergic contact dermatitis in at least two cases (52887,52888).

Psychiatric ...A case of night eating syndrome has been reported for a 41-year-old female who had been taking a gotu kola tincture (dose not specified) for 2 years. Symptoms resolved after gotu kola use was discontinued (52878).

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General ...Orally and intravaginally, Lactobacillus acidophilus is generally well tolerated.
Most Common Adverse Effects:
Orally: Mild gastrointestinal adverse effects.
Intravaginally: Vaginal discharge.
Serious Adverse Effects (Rare):
Orally: There is concern that L. acidophilus may cause infections in some people.

Dermatologic ...Orally, in one clinical trial, a combination of Lactobacillus acidophilus La-5, Lacticaseibacillus paracasei subsp. paracasei F19, and Bifidobacterium animalis subsp. lacltis BB-12 was associated with two cases of rash, one with itching. However, it is not clear if these adverse effects were due to L. acidophilus, other ingredients, the combination, or if the events were idiosyncratic (90236).

Gastrointestinal ...Orally, taking Lactobacillus acidophilus in combination with other probiotics may cause gastrointestinal side effects including epigastric discomfort (90239), abdominal pain (90239,90291,111785), dyspepsia (90239), flatulence (107497,107520), bloating (107497,111785), diarrhea (111785), vomiting (107537), and burping (90239); however, these events are uncommon.

Genitourinary ...Intravaginally, cream containing Lactobacillus acidophilus has been shown to cause increased vaginal discharge in about 5% of patients, compared to about 1% of patients receiving placebo cream (90237). Vaginal burning was reported by one person using intravaginal L. acidophilus and Limosilactobacillus fermentum in a clinical trial (111781).

Immunologic ...Since Lactobacillus acidophilus preparations contain live and active microorganisms, there is some concern that they might cause pathogenic infection in some patients. L. acidophilus has been isolated in some cases of bacteremia, sepsis, splenic abscess, liver abscess, endocarditis, necrotizing fasciitis, pancreatic necrosis, and meningoencephalitis. Most of these cases are thought to be due to the translocation of bacteria from other locations in the body in which they occur naturally, such as the oral cavity and gastrointestinal tract (107543,111782,111792). L. acidophilus endophthalmitis has been reported rarely (111787,111795). In one case, it was related to intravitreal injections for age-related macular degeneration in a 90-year-old female with an intraocular lens (111787). In another, it occurred following cataract surgery (111795).

(Read more about LACTOBACILLUS ACIDOPHILUS)