Bee Pollen Plus Energy [Discontinued] by Natural Factors

POSSIBLY INEFFECTIVE

• Athletic performance. Small clinical studies suggest that oral bee pollen may not improve athletic performance. Details: Clinical research in athletes shows that taking bee pollen supplements orally does not seem to improve athletic performance or stamina (7062,7063,33973).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral bee pollen for aging, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Allergic rhinitis (hay fever). Although there has been interest in using oral bee pollen for allergic rhinitis (hay fever), there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Amenorrhea. Although there has been interest in using oral bee pollen for amenorrhea, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Atopic dermatitis (eczema). Although there has been interest in using topical bee pollen for atopic dermatitis (eczema), there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Benign prostatic hyperplasia (BPH). Although there has been interest in using oral bee pollen for BPH, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Bleeding. Although there has been interest in using oral bee pollen for bleeding, including intracranial hemorrhage, there is insufficient reliable information about the clinical effects of bee pollen for these conditions.
• Breast cancer-related hot flashes. It is unclear if oral bee pollen is beneficial for the treatment of menopause-like symptoms in breast cancer patients. Details: Preliminary clinical research in breast cancer patients suggests that taking a combination of bee pollen and honey does not reduce hot flashes or other menopause-like symptoms when compared with honey alone (91983).
• Constipation. Although there has been interest in using oral bee pollen for constipation, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Diarrhea. Although there has been interest in using oral bee pollen for diarrhea, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Diaper rash. Although there has been interest in using topical bee pollen for diaper rash, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Dysmenorrhea. Although there has been interest in using oral bee pollen for dysmenorrhea, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Obesity. Although there has been interest in using oral bee pollen for obesity, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Oral mucositis. Although there has been interest in using oral bee pollen for oral mucositis, there is insufficient reliable information about the clinical effects of bee pollen for this purpose.
• Premenstrual syndrome (PMS). Oral bee pollen has only been studied in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking two tablets twice daily of a specific combination product (Female, Natumin Pharma) containing royal jelly 6 mg, bee pollen extract 36 mg, and bee pollen with pistil extract 120 mg per tablet over a period of 2 menstrual cycles seems to decrease some symptoms of PMS, including irritability, weight gain, and edema, when compared with placebo (12008). More evidence is needed to rate bee pollen for these uses.

(Read more about BEE POLLEN)

POSSIBLY EFFECTIVE

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

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about ELEUTHERO)

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

• Menopausal symptoms. Several clinical studies suggest that oral royal jelly, taken alone or in combination with other ingredients, modestly improves menopausal symptoms. It is unclear if topical royal jelly is beneficial for this use. Details: One clinical study in postmenopausal patients shows that taking royal jelly 1000 mg daily for 8 weeks reduces menopausal symptom scores by around 30% when compared with placebo (102527). Other small clinical studies show that taking one to two capsules of a specific combination product containing royal jelly and flower pollen (Melbrosia) daily for 12 weeks reduces menopausal symptoms and improves feelings of well-being when compared with baseline or placebo (18064,71956,72005). Another clinical trial in postmenopausal patients shows that taking two capsules of a specific combination product containing royal jelly, evening primrose oil, damiana, and ginseng (Lady 4) daily for 4 weeks decreases self-rated menopausal symptoms when compared with placebo (21003). Topical royal jelly has also been evaluated. A small clinical study in postmenopausal adults shows that applying vaginal cream containing royal jelly 15% daily for 12 weeks improves quality of life, sexual problems, and urinary problems similarly to vaginal estrogen cream 0.625 mg. However, estrogen cream improves vaginal atrophy better than royal jelly (92884).

POSSIBLY INEFFECTIVE

• Allergic rhinitis (hay fever). Oral royal jelly does not appear to prevent or treat symptoms of allergic rhinitis in children. Details: A clinical trial in children 5-16 years of age with allergic rhinitis shows that taking a specific royal jelly product (Bidro) 150 mg twice daily for 3-6 months before and during pollen season does not prevent or treat nasal congestion, sneezing, or eye discomfort when compared with placebo (71968).
• Diabetes. Oral royal jelly does not appear to improve glycemic control in patients with type 2 diabetes. Details: Most clinical research in patients with type 2 diabetes, along with a meta-analysis of five small clinical trials including patients with or without type 2 diabetes, shows that taking royal jelly 0.5-6 grams daily for 4-8 weeks does not improve markers of glycemic control such as fasting plasma glucose and glycated hemoglobin (HbA1c) (92879,92880,92881,102529).
• Physical performance. Oral royal jelly does not appear to improve physical performance in elderly nursing home residents. Details: A clinical trial in elderly nursing home residents shows that taking royal jelly 1.2 grams or 4.8 grams daily for one year does not improve hand grip strength, walking, or ability to stand on one leg when compared with placebo (95870).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. Although there has been interest in using topical royal jelly for androgenic alopecia, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Atherosclerosis. Although there has been interest in using oral royal jelly for atherosclerosis, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Athletic performance. Oral royal jelly has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Two small clinical trials in elite male swimmers and runners show that taking royal jelly 400 mg and coenzyme Q10 60 mg daily for 10 days does not improve high-intensity interval training performance when compared with placebo (109992,109993). These studies were small and may not have been adequately powered to detect a difference between groups.
• Cancer-related fatigue. It is unclear if oral royal jelly is beneficial for improving cancer-related fatigue. Details: A small clinical study in patients with solid (nonhematologic) malignancies shows that taking 5 mL of processed honey and royal jelly twice daily for 4 weeks reduces fatigue when compared with 5 mL of honey alone (92877).
• Chemotherapy-induced acral erythema. It is unclear if oral royal jelly is beneficial for preventing acral erythema from tyrosine kinase inhibitors (TKIs). Details: One small clinical trial in patients receiving TKI therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months does not reduce the risk of acral erythema when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference between groups.
• Chemotherapy-induced hepatotoxicity. It is unclear if oral royal jelly is beneficial for preventing hepatotoxicity from tyrosine kinase inhibitors (TKIs). Details: One small clinical trial in patients receiving TKI therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months does not reduce the risk of hepatotoxicity when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference between groups.
• Chemotherapy-induced nephrotoxicity. It is unclear if oral royal jelly is beneficial for preventing chemotherapy-induced nephrotoxicity. Details: A small clinical study in patients receiving two cycles of cisplatin therapy shows that taking royal jelly capsules daily may attenuate increases in serum creatinine and urea levels when compared with placebo. However, it is unclear if this effect is clinically significant; the increased levels that occurred in the placebo group were still within normal limits (95871). The validity of these results is also limited by the short study duration and lack of statistical comparison between groups. Another small clinical trial in patients receiving tyrosine kinase inhibitor therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months does not reduce the risk of kidney dysfunction when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference between groups.
• Chemotherapy-related fatigue. It is unclear if oral royal jelly is beneficial for preventing fatigue from tyrosine kinase inhibitors (TKIs). Details: One small clinical trial in patients receiving TKI therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months reduces the frequency of chemotherapy-related fatigue when compared with placebo (105773,105774).
• Cognitive impairment. Oral royal jelly has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in elderly patients with mild cognitive impairment shows that taking a specific combination product (Memo, Pharco Pharmaceuticals), which contains natural lyophilized royal jelly 750 mg, ginkgo leaf extract 120 mg, and Panax ginseng root extract 150 mg, daily for 4 weeks improves cognitive ability when compared with placebo (89712).
• Diabetic foot ulcers. Small clinical studies suggest that topical application of royal jelly plus panthenol may improve healing of diabetic foot ulcers. It is unclear if topical royal jelly alone is beneficial for this use. Details: One small clinical study shows that applying royal jelly 5% to a wound after conventional cleansing and debriding three times weekly for 3 months does not improve the healing of diabetic foot ulcers when compared with placebo (92882). However, other small clinical studies show that applying 1-3 grams of a specific combination ointment (Pedyphar) containing royal jelly and panthenol after conventional cleansing and debriding procedures twice weekly for up to 6 months may improve the healing of diabetic foot ulcers (71980,102526). In one of these studies, the rate of complete healing of life-threatening ulcers was 2.7-fold greater with this combination ointment when compared with panthenol alone (102526). Possible reasons for these discrepancies include the use of combination versus single ingredient ointments and the duration of treatment.
• Dry eye. It is unclear if oral royal jelly is beneficial in patients with dry eye. Details: A small clinical trial in Japanese patients with dry eye shows that taking enzyme-treated royal jelly 2.4 grams daily for 8 weeks does not improve tear stability or dry eye symptoms when compared with placebo (95869).
• Fractures. Although there has been interest in using oral royal jelly for healing of fractures, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Hepatitis. Although there has been interest in using oral royal jelly for hepatitis, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Male infertility. Intravaginal application of royal jelly has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in couples experiencing infertility due to asthenozoospermia shows that applying a saline solution containing royal jelly 3 grams, Egyptian bee honey 100 grams, and bee bread 1 teaspoon intravaginally before or after intercourse, starting one day after menstruation and continuing for 2 weeks, can increase the rate of pregnancy when compared with intrauterine insemination (55131). It is unclear if this effect is due to royal jelly, other ingredients, or the combination.
• Obesity. It is unclear if oral royal jelly is beneficial for reducing body weight in patients who are overweight or obese. Details: One small clinical study in overweight patients with type 2 diabetes shows that taking fresh royal jelly 1 gram daily for 8 weeks reduces body weight by around 2 kg and body mass index (BMI) by around 0.7 kg/m², as well as carbohydrate and total energy intake, when compared with placebo. However, the improvement is modest and may not be clinically significant (92878). Another small clinical study in overweight adults shows that taking royal jelly 1000 mg daily for 8 weeks does not reduce body weight, BMI, or appetite when compared with placebo (102528). However, this study may have been inadequately powered to detect a difference in these outcomes.
• Oral mucositis. It is unclear if oral royal jelly is beneficial for preventing or treating oral mucositis in patients receiving radiotherapy and/or chemotherapy. Details: One small clinical trial in patients receiving chemotherapy and radiotherapy shows that swishing and swallowing royal jelly 1 gram in two divided doses daily, in addition to standard rinses with benzydamine and nystatin, improves healing time of mild or moderate oral mucositis when compared with standard rinses alone (95867).
• Osteoporosis. It is unclear if oral royal jelly is beneficial in patients with osteoporosis. Details: A small clinical trial in postmenopausal adults shows that taking royal jelly powder 1000 mg, equivalent to 3000 mg of fresh royal jelly, daily for 6 months maintains bone mineral density (BMD) in the proximal femur and lumbar spine, while patients taking placebo saw significant reductions in lumbar spine BMD. Also, markers of bone turnover were significantly reduced with placebo, while significant changes in these markers were lacking in patients taking royal jelly (105775). It is unclear whether these findings can be generalized to patients with documented osteoporosis.
• Peptic ulcers. Although there has been interest in using oral royal jelly for peptic ulcers, there is insufficient reliable information about the clinical effects of royal jelly for this purpose.
• Premenstrual syndrome (PMS). It is unclear if oral royal jelly, taken alone or in combination with other ingredients, is beneficial in patients with PMS. Details: A small clinical study in healthy college students shows that taking royal jelly 1 gram daily starting on the first day of menstruation and continuing for two consecutive menstrual cycles improves PMS symptoms when compared with placebo (95873). However, methodological flaws associated with the study limit the validity of these results. A small clinical study shows that taking a specific combination product (Femal, Natumin Pharma), providing royal jelly 12 mg, bee pollen extract 72 mg, and bee pollen plus pistil extract 240 mg, twice daily over 2 menstrual cycles seems to decrease some symptoms of PMS including irritability, weight increases, and edema (12008). It is unclear if these effects are due to royal jelly, other ingredients, or the combination.
• Renal cell carcinoma. It is unclear if oral royal jelly is beneficial in patients with renal cell carcinoma. Details: One small clinical trial in patients receiving tyrosine kinase inhibitor (TKI) therapy for renal cell carcinoma shows that taking royal jelly 900 mg four times daily for 3 months reduces tumor size, improves chemotherapy-related fatigue and anorexia, and reduces the need for dose reduction or the discontinuation of therapy when compared with placebo (105773,105774). Royal jelly does not seem to reduce other TKI-related adverse effects, including gastrointestinal symptoms, oral mucositis, acral erythema, anemia, hepatotoxicity, or nephrotoxicity, when compared with placebo (105773). However, this study may have been inadequately powered to detect a difference in these outcomes. More evidence is needed to rate royal jelly for these uses.

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POSSIBLY SAFE ...when used orally and appropriately, short-term. Bee pollen has been safely used in clinical trials lasting up to 30 days (7062,7063,12008,33973). There is also preliminary evidence that taking 2 tablets twice daily of a specific combination product containing royal jelly 6 mg, bee pollen extract 36 mg, and bee pollen plus pistil extract 120 mg (Femal, Natumin Pharma) per tablet for up to 2 months seems to be safe (12008).

PREGNANCY: POSSIBLY UNSAFE
when used orally. There is some concern that bee pollen might have uterine stimulant effects (5,6,11); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

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

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

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

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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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POSSIBLY SAFE ...when used orally and appropriately, short-term. Royal jelly 1-4.8 grams daily for up to 1 year has been used in clinical research without reported adverse effects (95869,95870,102527,102528,105773,105774)....when used topically and appropriately for up to 6 months (71980,102526).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately for up to 6 months. A specific royal jelly product (Bidro) 150 mg twice daily has been used with apparent safety for 3-6 months in children 5-16 years of age (71968).

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

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WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D There is some concern that bee pollen might interact with warfarin and increase the risk of bleeding.  Details In one case report, a patient on warfarin had a stable international normalized ratio (INR) of 1.9-3.3 for 9 months. The patient's INR was found to be 7.1 after starting bee pollen granules one teaspoon twice daily for approximately one month. The patient's warfarin dose was decreased by approximately 11% in order to return the INR to the therapeutic range while continuing the bee pollen supplement (18063).

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

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

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

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might increase levels of drugs metabolized by CYP2C9.  Details In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9 (7532). This effect has not been reported in humans.

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

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

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

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

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

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

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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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ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, royal jelly might increase the risk of hypotension when taken with antihypertensive drugs.  Details Animal research suggests that royal jelly might lower blood pressure (71982,71963).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Royal jelly might increase the risk of bleeding when taken with warfarin.  Details In one case, an 87-year-old male who was previously stabilized on warfarin developed hematuria and was found to have an INR of 7.29 after taking a royal jelly supplement for one week (14303).

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General ...Orally, bee pollen seems to be well tolerated in most patients.
Serious Adverse Effects (Rare):
Orally: Acute hepatitis, allergic reactions, interstitial nephritis, kidney failure.

Dermatologic ...Orally, a case of photosensitivity has been reported for a 32-year-old patient who took a dietary supplement containing ginseng, goldenseal, bee pollen, and other ingredients. Symptoms included a pruritic, erythematous rash that was localized to the sun-exposed surfaces of the neck and extremities. Following treatment with topical and subcutaneous corticosteroids and discontinuation of the supplement, the skin rash slowly resolved. It is not known if this effect was due to the bee pollen, one of the other ingredients, or their combination (33954).

Hepatic ...Orally, there have been two cases of acute hepatitis associated with bee pollen use. One case involved ingestion of two tablespoons of pure bee pollen daily for several months. Another case involved ingestion of 14 tablets per day of a combination herbal product containing bee pollen, chaparral, and 19 other herbs for 6 weeks (1351). In this case, it is not known if bee pollen or another herb might have caused the adverse event.

Immunologic ...Patients with a history of seasonal pollen allergies, particularly allergies to plants in the Asteraceae/Compositae family, including ragweed, chrysanthemums, marigolds, daisies, and many other herbs, are at risk for serious allergic reactions to oral bee pollen. Allergic reactions can include itching, swelling, shortness of breath, lightheadedness, and anaphylaxis (5,6,11,13480,33952,33965,91981,91984,109991). In one case, exercise may have contributed to the reaction. A 15-year-old male developed generalized urticaria, facial angioedema, and dyspnea 30 minutes into a vigorous exercise session and an hour after ingesting bee pollen granules. The patient experienced abdominal cramps within minutes of consuming bee pollen on 3 previous occasions and had a positive skin prick test for bee pollen after the anaphylactic reaction (109991). Allergy symptoms due to chronic intake of bee pollen include gastrointestinal and neurologic symptoms and eosinophilia (2627,33964).
A case of allergic eosinophilic gastropathy has been reported for a 5 year-old child who was given bee pollen daily to strengthen the immune system. Symptoms included abdominal pain, vomiting, and swelling of the eyelids and legs (91981).

Neurologic/CNS ...Orally, there is one report of dizziness in a patient who took a combination product containing royal jelly, bee pollen extract, and a bee pollen plus pistil extract (12008). It is not known if this effect was due to the bee pollen, another ingredient, or the combination.

Renal ...Orally, there is one report of a patient taking a bee pollen-containing supplement for greater than 5 months who developed breathing difficulties, edema with weight gain, and loss of appetite. The patient was diagnosed with interstitial nephritis and drug-induced acute kidney failure. The supplement was discontinued and the patient was started on hemodialysis. The patient improved after several sessions of hemodialysis (18068).

Other ...Although some research has shown a lack of mycotoxins in twenty samples of bee pollen, analysis of other ready-to-eat bee pollen products have revealed contamination with potential mycotoxin producing species, including Penicillium verrucosum, Aspergillus niger aggregate, Aspergillus carbonarius, Aspergillus ochraceus, Aspergillus flavus, Aspergillus parasiticus, and Alternaria spp. (33959,33961).

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

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

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

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

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

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

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

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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 topically, royal jelly seems to be well tolerated.
Most Common Adverse Effects:
Orally: Dyspnea, eczema, oral allergy syndrome, pruritus, and urticaria in people with a history of asthma or atopy.
Topically: Contact dermatitis and skin irritation.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis, status asthmaticus, and death in people with a history of asthma or atopy.

Gastrointestinal ...There is one case report of hemorrhagic colitis with abdominal pain, bloody diarrhea with concomitant hemorrhagic and edematous mucosa of the sigmoid colon after ingestion of royal jelly. Symptoms resolved within 2 weeks following discontinuation of royal jelly and conservative treatment (3516).

Immunologic ...In people with a history of atopy or asthma, royal jelly taken orally appears to cause a high rate of allergic symptoms including pruritus, urticaria, eczema, eyelid and facial edema, conjunctivitis, rhinorrhea, dyspnea, oral allergy syndrome, and asthma (7314,7315,7316,10623,95872). In severe cases, royal jelly can cause status asthmaticus, anaphylaxis, and death (792,7315,7316,10623,10624,108511). Allergic symptoms are associated with IgE-mediated hypersensitivity reactions (3513,10623).
Topically, skin irritation, exacerbation of dermatitis, or contact dermatitis may occur (791).
From occupational exposure, royal jelly can cause allergic rhinoconjunctivitis and asthma (95868).

Neurologic/CNS ...There is one report of dizziness in a patient who took a combination product containing royal jelly, bee pollen extract, and a bee pollen plus pistil extract (12008).

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