Aloe Latex 140 mg with Fennel by Nature's Way

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.

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POSSIBLY EFFECTIVE

• Dysmenorrhea. Taking fennel oil or extract by mouth may reduce pain in patients with primary dysmenorrhea. This benefit may be similar to ibuprofen or mefenamic acid. Details: Two separate meta-analyses in patients with primary dysmenorrhea show that taking fennel oil or fennel extract for 1-6 menstrual cycles reduces dysmenorrhea pain when compared with placebo. Improvement in pain was similar when compared with ibuprofen or mefenamic acid. In the included studies, doses of fennel oil ranged from 3-30 drops every 4-8 hours, and doses of fennel extract ranged from 30-230 mg daily (104196,108972). However, most studies included in these meta-analyses were small and low-quality, and all studies were conducted in Iran. Higher quality studies in other geographic locations are needed to confirm these findings.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there has been interest in using oral fennel for anxiety, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Bronchitis. Although there has been interest in using oral fennel for bronchitis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cancer. Although there has been interest in using oral fennel for cancer prevention, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cholera. Although there has been interest in using oral fennel for cholera, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Colic. Small clinical studies suggest that oral fennel may reduce crying time in infants with colic. However, most research to date has evaluated fennel in combination with other ingredients. Details: A meta-analysis of three small clinical studies shows that giving fennel to infants with colic can reduce crying time by about 72 minutes daily when compared with placebo (97497). However, the studies included in this meta-analysis were at medium to high risk of bias, and the placebo response rate was high in all of the included studies. Additionally, two of the three studies evaluated combination products (16735,19715,49428). In the one study that used fennel alone, administering 5-20 mL of fennel seed oil 0.1% emulsion daily for one week led to colic relief in 65% of infants, compared with 24% of infants receiving placebo (49428). The other studies evaluated fennel in combination with lemon balm and German chamomile (ColiMil) or in combination with chamomile, vervain, licorice, and lemon balm (Calma-Bebi, Bonomelli). These combination products produced a response in 57% to 85% of infants, compared with 26% to 49% of infants receiving placebo (16735,19715).
• Constipation. Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small crossover trial in patients with constipation shows that drinking an herbal tea containing 3 grams of a combination of fennel, anise, elderberry, and senna daily for 5 days can decrease colonic transit time, increase the number of daily evacuations, and improve the perception of bowel function when compared with placebo (49494). Another small clinical study in elderly patients with constipation shows that drinking a specific tea (Smooth Move, Traditional Medicinals) containing fennel, senna, licorice, orange peel, cassia cinnamon, coriander, and ginger for 28 days can increase the number of bowel movements when compared to baseline (46196). The validity of this finding is limited by the lack of a comparator group. Additionally, a small clinical study in patients aged 60-65 years with functional constipation shows that taking a traditional Iranian combination product containing 5 grams each of fennel seed and rose flower, dissolved in water twice daily before meals for 4 weeks, improves constipation severity and stool consistency when compared with polyethylene glycol 10 grams. Improvements in constipation severity persisted in both groups 4 weeks after treatment completion (108973). However, polyethylene glycol is usually taken at a higher dose of 17 grams daily, limiting the validity of these findings.
• Cough. Although there has been interest in using oral fennel for cough, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dementia. Although there has been interest in using oral fennel for dementia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Diabetes. Although there has been interest in using oral fennel for diabetes, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dyspepsia. Although there has been interest in using oral fennel for dyspepsia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Flatulence. Although there has been interest in using oral fennel for flatulence, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Hirsutism. It is unclear if topical fennel is beneficial in patients with hirsutism. Details: A small clinical study in females with male pattern body hair due to unknown causes shows that applying a fennel 2% cream twice daily for 12 weeks can reduce hair diameter by approximately 19% when compared with placebo (49429).
• Insomnia. Although there has been interest in using oral fennel for insomnia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Irritable bowel syndrome (IBS). Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults with either diarrhea- or constipation-predominant IBS shows that taking two capsules containing fennel essential oil 25 mg and curcumin 42 mg per capsule (CU-FEO, Alfa Wassermann S.p.A.) twice daily for 30 days improves overall ratings of abdominal pain, abdominal distention, and quality of life by 24% when compared with placebo (97422).
• Lactation. Although there has been interest in using oral fennel to stimulate breastmilk production, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Menopausal symptoms. Small clinical studies suggest that oral fennel oil or fennel seed powder may modestly improve menopausal symptoms. Details: One small clinical trial in adults with medium severity menopausal symptoms shows that taking fennel essential oil 60 mg daily for 8 weeks improves scores on the Menopause Rating Scale when compared with a sunflower oil placebo (97498). Another small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks improves scores on the Kupperman Menopausal Index when compared with placebo (104198). Fennel has also been evaluated in combination with other ingredients. One small clinical study shows that taking a combination of fennel 120 mg, chamomile 1000 mg, and saffron 60 mg daily for 12 weeks reduces physical, psychological, and urogenital symptom scores on the Menopause Rating Scale when compared with placebo or lower doses of the combination (103628). Additionally, a moderate-sized clinical study in postmenopausal women conducted in Iran shows that taking combined fennel and valerian extract 500 mg twice daily for 8 weeks modestly improves self-reported scores for frequency and severity of hot flashes but does not improve sleep quality or duration of hot flashes when compared with placebo (112369). However, it is unclear if these benefits are due to fennel, other ingredients, or the combination.
• Nausea and vomiting. Although there has been interest in using oral fennel for nausea and vomiting, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Nocturnal enuresis. Although there has been interest in using oral fennel for nocturnal enuresis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Osteoarthritis. It is unclear if oral fennel extract is beneficial in patients with knee osteoarthritis. Details: A small clinical trial in females with osteoarthritis of the knee shows that taking powdered fennel extract 800 mg daily for 2 weeks reduces pain and disability scores, but not stiffness, when compared with placebo (104199).
• Polycystic ovary syndrome (PCOS). It is unclear if oral fennel is beneficial in patients with PCOS. Details: A small clinical study in patients with PCOS shows that taking two fennel capsules, containing anethole 21-27 mg per capsule, daily along with a hypocaloric standard diet or a hypocaloric high-protein diet for 3 months does not reduce body weight or improve androgenic parameters such as testosterone levels, sex hormone-binding globulin levels, or free androgen index, when compared with these diets plus placebo (104197). Fennel has also been evaluated in combination with other ingredients. A clinical study in patients with oligomenorrhea due to PCOS shows that taking a traditional combination product (Aslagh) containing equivalent amounts of essential oils of fennel, wild carrot seeds, and Vitex agnus-castus fruit for 3 months, either alone or in combination with metformin, improves rates of menstrual bleeding and menstrual cyclicity similarly to metformin alone. All three groups experienced a significant improvement from baseline. Aslagh was taken as two, 500-mg capsules twice daily, except during menses; metformin was titrated over one week to a dose of 500 mg three times daily (108974). Additionally, a moderate-sized clinical study in patients with PCOS shows that taking fennel 60 mg and Elwendia persica 25 mg twice daily for 4 months modestly improves number of ovarian follicles and body mass index when compared with placebo; however, when compared to baseline, the combination also improves hirsutism scores and menstrual cycle duration and interval (112370). It is unclear if these effects are due to fennel, other ingredients, or the combination.
• Rheumatoid arthritis (RA). Although there has been interest in using oral fennel for RA, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Sexual desire. It is unclear if oral fennel is beneficial for improving sexual desire. Details: A small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks does not improve scores on the Hurlbert Index of Sexual Desire when compared with placebo (104198).
• Sunburn. It is unclear if topical fennel emulsion is beneficial for preventing sunburn. Details: A small clinical study shows that applying a fennel 5% emulsion topically prior to ultraviolet (UV) exposure can reduce sunburn by 65% when compared with a control (49518).
• Upper respiratory tract infection (URTI). Although there has been interest in using oral fennel for upper respiratory tract infections, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Vaginal atrophy. It is unclear if intravaginal application of fennel cream is beneficial in patients with vaginal atrophy. Details: A small clinical study in postmenopausal adults shows that applying 5 grams of a fennel 5% cream to the vagina once daily for 8 weeks seems to reverse vaginal thinning, improve vaginal pH, and reduce symptoms of vaginal atrophy such as itching, dryness, and pain with intercourse when compared with placebo (92509). Patients in the fennel group also rated their sexual function to be improved when compared with those receiving placebo (97496). More evidence is needed to rate fennel for these uses.

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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. Fennel has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when fennel essential oil or extract is used orally and appropriately, short-term. Twenty-five drops (about 1.25 mL) of fennel fruit extract standardized to fennel 2% essential oil has been safely used four times daily for 5 days (49422). Also, two 100 mg capsules each containing fennel 30% essential oil standardized to 71-90 mg of anethole has been safely used daily for 8 weeks (97498). Powdered fennel extract has been used with apparent safety at a dose of 800 mg daily for 2 weeks (104199). ...when creams containing fennel 2% to 5% are applied topically (49429,92509).

CHILDREN: POSSIBLY SAFE
when combination products containing fennel are used to treat colic in infants for up to one week. Studied products include up to 20 mL of a fennel seed oil emulsion; a specific product (ColiMil) containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg; and up to 450 mL of a specific tea (Calma-Bebi, Bonomelli) containing fennel, chamomile, vervain, licorice, and lemon balm (16735,19715,49428).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Observational research has found that regular use of fennel during pregnancy is associated with shortened gestation (100513).

LACTATION: POSSIBLY UNSAFE
when used orally. Case reports have linked consumption of an herbal tea containing extracts of fennel, licorice, anise, and goat's rue to neurotoxicity in two breast-feeding infants. The adverse effect was attributed to anethole, a constituent of fennel and anise (16744). However, levels of anethole were not measured in breastmilk, and the herbal tea was not tested for contaminants. Furthermore, other adverse effects related to use of fennel during lactation have not been reported. However, until more is known, avoid using.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D 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.

(Read more about ALOE)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details Animal research suggests that fennel oil has antithrombotic and antiplatelet effects (31415,49445).

CIPROFLOXACIN (Cipro) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.  Details Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin (6135).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.  Details In vitro research suggests that fennel inhibits CYP3A4 enzyme activity (38375,49468). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.  Details Some constituents of fennel have estrogenic activity (11), which may interfere with the antiestrogenic activity of tamoxifen.

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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).

(Read more about ALOE)

General ...Orally and topically, fennel seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, photosensitivity, and allergic reactions in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Seizures.

Dermatologic ...Advise patients to avoid excessive sunlight or ultraviolet light exposure while using fennel (19). Allergic reactions affecting the skin such as atopic dermatitis and photosensitivity may occur in patients who consume fennel (6178,49507).

Gastrointestinal ...Orally, fennel may cause gastrointestinal complaints, including nausea and vomiting (19146,104196).

Hematologic ...Methemoglobinemia has been reported in four infants following intoxication related to ingestion of a homemade fennel puree that may have been made from improperly stored fennel (49444).

Immunologic ...A case report describes an 11-year-old male who developed an allergy to fennel-containing toothpaste. Immediately after using the toothpaste, the patient experienced sneezing, coughing, itchy mouth, rhinorrhea, nasal congestion, wheezing, difficulty breathing, and palpitations, which resolved within 10 minutes of spitting out the toothpaste and rinsing the mouth. In challenge tests, the patient reacted to chewing fresh fennel root, but not ground fennel seeds (103822).

Neurologic/CNS ...Orally, fennel oil has been associated with tonic clonic and generalized seizures (12868). New-onset cluster headaches are reported in a 24-year-old female while using a toothpaste containing fennel and camphor for 3 months. The headaches resolved upon stopping the toothpaste (112368). It is unclear if this adverse effect can be attributed to fennel, camphor, or the combination.

Pulmonary/Respiratory ...Orally, fennel and fennel seed have been reported to cause bronchial asthma (49478).

(Read more about FENNEL)